Beyond single-marker analyses: mining whole genome scans for insights into treatment responses in severe sepsis.

Management of severe sepsis, an acute illness with high morbidity and mortality, suffers from the lack of effective biomarkers and largely empirical predictions of disease progression and therapeutic responses. We conducted a genome-wide association study using a large randomized clinical trial cohort to discover genetic biomarkers of response to therapy and prognosis utilizing novel approaches, including combination markers, to overcome limitations of single-marker analyses. Sepsis prognostic models were dominated by clinical variables with genetic markers less informative. In contrast, evidence for gene-gene interactions were identified for sepsis treatment responses with genetic biomarkers dominating models for predicting therapeutic responses, yielding candidates for replication in other cohorts.

Monitoring of circulating monocyte HLA-DR expression in a large cohort of intensive care patients: relation with secondary infections.

INTRODUCTION: The reports of an early and profound acquired immunodepression syndrome (AIDs) in ICU patients had gained sufficient credence to modify the paradigm of acute inflammation. However, despite several articles published on AIDs and its assessment by monocytic HLA-DR monitoring, several missing informations remained: 1-Which patients' are more prone to benefit from mHLA-DR measurement, 2-Is the nadir or the duration of the low mHLA-DR expression the main parameter to consider? 3-What are the compared performances of leukocytes' count analyses (lymphocyte, monocyte). MATERIAL AND METHOD: We conducted an observational study in a surgical ICU of a French tertiary hospital. A first mHLA-DR measurement (fixed flow cytometry protocol) was performed within the first 3 days following admission and a 2nd, between day 5 and 10. The other collected parameters were: SAPS II and SOFA scores, sex, age, comorbidities, mortality and ICU-acquired infections (IAI). The associations between mHLA-DR and outcomes were tested by adjusted Fine and Gray subdistribution competing risk models. RESULTS: 1053 patients were included in the study, of whom 592 had a 2nd mHLA-DR measurement. In this cohort, 223 patients (37.7%) complicated by IAI. The initial decrement in mHLA-DR was not associated with the later occurrence of IAI, (p = 0.721), however, the persistence of a low mHLA-DR (< 8000 AB/C), measured between day 5 and day 7, was associated with the later occurrence of IAI (p = 0.01). Similarly, a negative slope between the first and the second value was significantly associated with subsequent IAI (p = 0.009). The best performance of selected markers was obtained with the combination of the second mHLA-DR measurement with SAPSII on admission. Persisting lymphopenia and monocytopenia were not associated with later occurrence of IAI. CONCLUSION: Downregulation of mHLA-DR following admission is observed in a vast number of patients whatever the initial motif for admission. IAI mostly occurs among patients with a high severity score on admission suggesting that immune monitoring should be reserved to the most severe patients. The initial downregulation did not preclude the later development of IAI. A decreasing or a persisting low mHLA-DR expression below 8000AB/C within the first 7 days of ICU admission was independently and reliably associated with subsequent IAI among ICU patients with performances superior to leukocyte subsets count alone.

Neurosurgery and elderly: analysis through the years.

The aging of the population in westernized countries constitutes an important issue for the health systems struggling with limited resources and increasing costs. Morbidity and mortality rates reported for neurosurgical procedures in the elderly vary widely. The lack of data on risk benefit ratios may result in challenging clinical decisions in this expanding group of patients. The aim of this paper is to analyze the elderly patients cohort undergoing neurosurgical procedures and any trend variations over time. The medical records of elderly patients (defined as an individual of 70 years of age and over) admitted to the Neurosurgical and Neuro-ICU Departments of a major University Hospital in Paris over a 25-year period were retrospectively reviewed. The analysis included: (1) number of admissions, (2) percentage of surgically treated patients, (3) type of procedures performed, (4) length of hospital stay, and (5) mortality. The analysis showed a progressive and significant increase in the proportion of elderly presenting for neurosurgical elective and/or emergency procedures over the last 25 years. The number of procedures on patients over 70 years of age increased significantly whereas the mortality dropped. Though the length of hospital stay was reduced, it remained significantly higher than the average stay. The types of procedures also changed over time with more craniotomies and endovascular procedures being performed. Age should not be considered as a contraindication for complex procedures in neurosurgery. However, downstream structures for postoperative elderly patients must be further developed to reduce the mean hospital stay in neurosurgical departments because this trend is likely to continue to grow.

Uncontrollable high-frequency tachypnea: a rare and nearly fatal complication of endoscopic third ventriculostomy: case report and literature review.

BACKGROUND: Endoscopic third ventriculostomy (ETV) is considered a safe procedure although it carries its rate of risks and complications that may occasionally be life-threatening. CASE REPORT: This is a report about a 48-year-old woman presenting with progressive gait unsteadiness, weakness of the lower extremities and cognitive impairment due to tri-ventricular hydrocephalus. This was treated with standard ETV. In the immediate post-operative period the patient developed a severe and uncontrollable tachypnea requiring sedation, intubation and mechanical ventilation. CONCLUSION: Tachypnea may be an early complication after standard ETV and although its mechanism remains yet unclear, we speculate that it may be related to excessive traction and/or surgical manipulation of the floor of the third ventricle. Supportive care with mechanical ventilation is the mainstay of treatment until spontaneous normalization of the respiratory mechanism occurs.

Acute effects of tumor necrosis factor on the microcirculation in rat cremaster muscle.

The acute effects of TNF on the microcirculation were studied by in vivo microscopy in rat cremaster muscle. The changes in arteriolar diameter after topical administration of recombinant TNF (rTNF; 10(-4)-10(4) ng/ml) were studied in second-, third-, and fourth-order arterioles (A2-A4) whose mean diameters under control conditions were 64.3, 30.7, and 14.8 microns respectively. rTNF induced a concentration-dependent vasodilation whose amplitude was largest for the smallest arterioles. At the highest concentration tested, arteriolar diameter increased by 21, 29, and 41% of control diameter for the A2, A3, and A4 arterioles, respectively. Indomethacin or mefenamic acid, two structurally different prostaglandin synthesis inhibitors, markedly inhibited the degree of vasodilation induced by rTNF in the three arteriolar orders. As regards the effect of rTNF on vasoconstriction in response to norepinephrine, vasoconstriction was greatest for the smallest arterioles, and did not change 10 min after rTNF administration for any of the three arteriolar orders. We conclude that (a) rTNF has a direct vasodilatory effect which is greatest in the smallest arterioles, (b) this vasodilation is at least partly mediated by prostaglandins, and (c) administration of rTNF in itself does not acutely alter the response of the arterioles to vasopressive drugs.

Activated macrophages depress the contractility of rabbit carotids via an L-arginine/nitric oxide-dependent effector mechanism. Connection with amplified cytokine release.

Inflammatory mediators released by macrophages (M phi) are believed to be involved in septic vasoplegia. To investigate the effect of M phi on vascular reactivity, excised rabbit carotids were exposed intraluminally either to peritoneal rabbit M phi, activated by 18 h of incubation with 1 microgram/ml lipopolysaccharide, or to the supernatants (SPN) derived from them. The contractile responses to phenylephrine (PE, 10(-6) M) were determined by measuring changes in diameter using an ultrasonic microdimensiometer 1, 2, and 3 h after the first control contraction. In control arteries (n = 12), PE-induced contractions were, respectively, 102.9 +/- 3.3%, 95.2 +/- 4.1%, and 89.7 +/- 3.8% of the first contraction, after 1, 2, and 3 h. Activated M phi significantly reduced PE-stimulated contractions after as little as 1 h of carotid exposure (percentage of controls at 1, 2, or 3 h: 74.1 +/- 5.6, 57.2 +/- 5.2, and 34.2 +/- 5.6, n = 10, P less than 0.001). The activated macrophage-derived SPN took longer to diminish carotid contractility than the M phi themselves, and became significant only after 2 h. The greater effect of M phi might be due to cooperation between M phi and vascular cells, as suggested by the amplified interleukin-1 release observed after M phi infusion. The presence of the endothelium partially protected carotid contractility from depression by activated M phi. Extraluminal addition of NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis prevented this depression in arteries with or without endothelium. No products of the oxidative pathway of L-arginine were detected in rabbit activated M phi. These results suggest that activation of this pathway in smooth muscle cells seems to be involved in vascular hypocontractility.

[Severe cervical skin and soft tissue infections and necrotizing fasciitis]. / Dermohypodermites bactériennes nécrosantes et fasciites nécrosantes. Cellulites ORL.

Cervical severe skin and soft tissue infections and necrotizing fasciitis originate from dental or pharyngeal infections. When compared to other forms of skin and soft tissue infections, they are recognized late, usually after one week of evolution often in a patient receiving antibiotic treatments. Extensions toward adjacent anatomical structures including mediastinum lead to a life-threatening prognosis. The cutaneous appearance of these severe infections is usually inflammatory cervical signs combined to facial oedema. These moderate clinical signs require immediate surgery after CT scan imaging.

Inspiratory impedance during active compression-decompression cardiopulmonary resuscitation: a randomized evaluation in patients in cardiac arrest.

BACKGROUND: Blood pressure is severely reduced in patients in cardiac arrest receiving standard cardiopulmonary resuscitation (CPR). Although active compression-decompression (ACD) CPR improves acute hemodynamic parameters, arterial pressures remain suboptimal with this technique. We performed ACD CPR in patients with a new inspiratory threshold valve (ITV) to determine whether lowering intrathoracic pressures during the "relaxation" phase of ACD CPR would enhance venous blood return and overall CPR efficiency. METHODS AND RESULTS: This prospective, randomized, blinded trial was performed in prehospital mobile intensive care units in Paris, France. Patients in nontraumatic cardiac arrest received ACD CPR plus the ITV or ACD CPR alone for 30 minutes during advanced cardiac life support. End tidal CO(2) (ETCO(2)), diastolic blood pressure (DAP) and coronary perfusion pressure, and time to return of spontaneous circulation (ROSC) were measured. Groups were similar with respect to age, gender, and initial rhythm. Mean maximal ETCO(2), coronary perfusion pressure, and DAP values, respectively (in mm Hg), were 13.1+/-0.9, 25.0+/-1.4, and 36.5+/-1.5 with ACD CPR alone versus 19.1+/-1.0, 43.3+/-1.6, and 56.4+/-1.7 with ACD plus valve (P<0.001 between groups). ROSC was observed in 2 of 10 patients with ACD CPR alone after 26.5+/-0.7 minutes versus 4 of 11 patients with ACD CPR plus ITV after 19.8+/-2.8 minutes (P<0.05 for time from intubation to ROSC). Conclusions-Use of an inspiratory resistance valve in patients in cardiac arrest receiving ACD CPR increases the efficiency of CPR, leading to diastolic arterial pressures of >50 mm Hg. The long-term benefits of this new CPR technology are under investigation.

Activation of cardiac endothelium as a compensatory component in endotoxin-induced cardiomyopathy: role of endothelin, prostaglandins, and nitric oxide.

BACKGROUND: In view of growing evidence of an important endothelial paracrine regulation of cardiac function, the present study investigated the role of cardiac endothelium-derived endothelin-1 (ET-1), prostaglandins, and nitric oxide (NO) during endotoxin-induced cardiomyopathy in rabbits. METHODS AND RESULTS: Immunohistochemical studies showed a marked transient coinduction of the inducible isoforms of NO synthase (NOS-2) and cyclooxygenase (COX-2) in endocardial endothelium and coronary arteriolar endothelium of hearts 12 hours after intravenous administration of lipopolysaccharide (LPS+12h); staining for both isoforms was much weaker 24 hours later (LPS+36h). Nitrotyrosine localization was similar to that of NOS-2, suggesting a NOS-2-related endothelial formation of peroxynitrite in septic hearts. Contractile performance of papillary muscles was depressed in both LPS-treated groups. In the LPS+12h group, however, isometric twitches were significantly prolonged (482+/-14 versus 420+/-14 ms in the saline-treated group, P<0.005). This twitch prolongation was completely reversed by simultaneous administration of BQ-123 and indomethacin to block endogenous ET-1 and prostaglandins, respectively. In addition, in the LPS+12h group, myocardial inotropic responsiveness to exogenous ET-1 was enhanced (P<0.01). CONCLUSIONS: Cardiac endothelial activation and myocardial sensitization to endothelium-derived mediators may be part of an adaptive response in the early (12 hours) stages of septic cardiomyopathy.

Common carotid haemodynamic and metabolic effects of acutely administered nifedipine in human subarachnoid haemorrhage.

Although the drugs known as "calcium antagonists" exert inhibitory actions on vascular smooth muscle, there are no quantitative data concerning the clinical use of these vasodilator agents in human subarachnoid haemorrhage. In the present clinical study, we have measured the effects of nifedipine (20 mg tablet) on common carotid artery diameter (D) blood flow velocity (V) common carotid blood flow (CCBF) as an index of cerebral blood flow, systolic (Qs) and diastolic (Qd) blood flow fractions using a pulsed Doppler apparatus and on carotid arterial pressure (CAP), heart rate (HR) and oxygen consumption (VO2). Eight patients with subarachnoid haemorrhage were studied during anaesthesia for cerebral angiography. Thirty minutes after sublingual nifedipine, diameter (P less than 0.05), blood flow velocity (P less than 0.001), CCBF (P less than 0.001), Qs (P less than 0.05), and Qd (P less than 0.05) increased with a decrease in Qs/Qd ratio (P less than 0.05). carotid vascular resistance (CVR) fell (P less than 0.02) and oxygen consumption of the brain increased (P less than 0.01). Systolic, diastolic, and mean carotid blood pressure, heart rate, and arteriovenous difference in oxygen were unchanged. The increase in CCBF was closely correlated with the vascular resistance in the control state (r = 0.928, P less than 0.001) and with oxygen consumption (r = 0.869, P less than 0.001). We conclude that in vivo, nifedipine exerts a preferential action on cerebral vessels, vasodilating large arteries and arterioles. This action is more powerful if the vessels are already vasoconstricted. Thus, the use of nifedipine could be fruitful in cerebral ischaemia that is secondary to subarachnoid haemorrhage.

Effect of modifying nitric oxide pathway on liver circulation in a rabbit endotoxin shock model.

The role of nitric oxide (NO) inhibition on liver circulation during sepsis is unknown. To answer this question, we studied the effects of L-arginine (the substrate for the NO synthase), linsidomine (a direct NO donor), and N omega-nitro-L-arginine (an NO inhibitor) on the liver circulation in anesthetized rabbits previously injected with endotoxin (Escherichia coli, Salmonella enteridis, and Salmonella minnesota, 400 micrograms each). After endotoxin administration, and without fluid resuscitation, rabbits showed a hypodynamic shock with decrease in mean arterial pressure (MAP) and aortic blood flow velocity. Portal vein blood flow velocity decreased, whereas hepatic artery blood flow velocity increased. Saline or treatments were injected, 75 min after endotoxin administration. In saline-treated rabbits, MAP, aortic and portal vein blood flow velocities remained steady but hepatic artery blood flow velocity decreased. Only N omega-nitro-L-arginine (7.5 mg/kg, intravenously) significantly increased MAP compared to saline treatment. However, aortic, portal vein, and hepatic artery blood flow velocities were lower in rabbits treated with N omega-nitro-L-arginine than in saline-treated rabbits. L-Arginine (600 mg/kg, intravenously) increased aortic blood flow and portal vein blood flow velocity with no change on hepatic artery blood flow velocity. In contrast, linsidomine (1 mg) increased both hepatic flows. These results show that NO inhibition after endotoxin injection reduces systemic and liver flows, while NO release from linsidomine improves them. These findings question the usefulness of NO inhibition during septic shock, particularly as hepatic failure frequently occurs in the evolution of the disease.

Ex vivo T-lymphocyte derived cytokine production in SIRS patients is influenced by experimental procedures.

Ex vivo production of interleukin-2 (IL-2), IL-4, IL-5, and IL-10 by peripheral blood mononuclear cells (PBMC) was studied in 13 septic patients with infectious systemic inflammatory response syndrome (SIRS) and 13 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) (noninfectious SIRS). We have investigated the levels of cytokines after activation by either concanavalin A (ConA), phytohemagglutinin (PHA), or anti-CD3 antibodies. In whole blood assays, ConA-induced IL-10 was significantly reduced in both groups of patients compared with healthy controls. In sepsis patients, IL-2, IL-5, and IL-10 productions by isolated PBMC were diminished on ConA-induced activation but not in response to PHA and anti-CD3; in CPB patients, only anti-CD3-induced IL-10 production was significantly reduced. Our data indicate that subtle modifications of the reactivity of circulating cells occur during infectious and noninfectious SIRS. Production of both Th1 and Th2 cytokines can be down-regulated; however, the nature of the SIRS, of the cell population, and of the activator may influence the observation.

Alveolar neutrophil oxidative burst and beta2 integrin expression in experimental acute pulmonary inflammation are not modified by inhaled nitric oxide.

It was recently proposed that nitric oxide (NO) inhalation interferes with polymorphonuclear neutrophil (PMN) activation status during acute pulmonary inflammation, although variable results have been observed considering timing of NO administration, species, and model differences. After intratracheal administration of lipopolysaccharide (LPS) in rats, we characterized pulmonary inflammatory reaction (lung wet, dry, and wet to dry weights) and, using flow cytometry, the activation status (H2O2 production and beta2 integrin CD11b/CD18 expression) of PMN obtained from blood and from bronchoalveolar lavage (BAL). Eight hours after LPS injection, rats received for an additional 10 h, at a same Fio2 (85%), either 15 parts per million NO or the same gas flow of nitrogen. We found that 18 h after LPS, lung wet, dry, and wet-to-dry weights, H2O2 production, and CD11b/CD18 expression were increased. PMN obtained from BAL were highly activated as evidenced by an already maximal expression of the beta2 integrin CD11b/CD18, whereas the high H2O2 production at basal state could be further enhanced after ex vivo stimulation. Blood PMN were not different from control cells at basal state; however, their increased capacity to be stimulated ex vivo suggested an in vivo priming effect of intratracheal LPS. In conclusion, inhaled NO, given with a high FiO2, in the presence of this established endotoxinic lung injury did not reverse the markers of PMN activation studied nor lung edema formation in this rat model.

Monitoring the effect of CPAP on left ventricular function using continuous mixed-blood saturation.

The hypothetic benefit of CPAP on cardiac performance and on a reduction in VO2 was tested in a patient before heart transplantation after acute myocardial infarction using continuous SvO2 monitoring. The CPAP added to inotropic support (enoximone plus dobutamine) and intraaortic balloon pumping dramatically increased SvO2 in relation to both an increase in cardiac output and a decrease in VO2 secondary to respiratory work reduction, validating the initial hypotheses.

Interest of a therapeutic optimization strategy in severe ARDS.

STUDY OBJECTIVE: Evaluate the interest of the response to a therapeutic optimization as a predictor of prognosis in ARDS. DESIGN: Prospective study. SETTING: ICU of a University Hospital. PATIENTS: Thirty-six consecutive patients with severe ARDS addressed for extracorporeal carbon dioxide removal (ECCO2R). INTERVENTIONS: We studied the response during the first 2 days after arrival to the therapeutic optimization strategy consisting in a combination of the following: (1) decrease in extravascular lung water (diuretics or hemofiltration); (2) selection of the best ventilatory mode; (3) permissive hypercarbia; and (4) correction of hypoxemia by alveolar recruitment, additional continuous oxygen insufflation, body position changes (prone position), inhaled nitric oxide, enhancement of hypoxic pulmonary vasoconstriction with almitrine, and drainage of pleural or mediastinal effusions. In patients remaining severely hypoxemic despite these modalities, ECCO2R was then proposed. MEASUREMENTS AND RESULTS: Thirty-six patients were addressed after 8.3+/-5.5 days of mechanical ventilation. On arrival, mean simplified acute physiologic score was 46.8+/-14.2, multiple system organ failure score was 1.8+/-1.6, Murray score was 3.4+/-0.4, PaO2 was 75.3+/-31.3 (fraction of inspired oxygen [FIO2]=1) for a positive end-expiratory pressure level of 12.3+/-3.4 cm H2O. Nineteen of 36 patients improved their gas exchange within 2 days and their mortality was 21%. The seventeen remaining patients did not improve PaO2/FIO2; PaCO2 and airway pressures remained high and their mortality was 88%. This different response to therapeutic optimization appeared using stepwise logistic regression as the most predictive factor for mortality (p<0.05). CONCLUSIONS: In patients with severe ARDS, the response to an early performed therapeutic optimization used to improve hypoxemia appeared to be a highly discriminant factor distinguishing deceased from surviving patients.

Doppler cardiac output and left ventricular performance after cardiac surgery. Pulsed Doppler ascending aorta and pulmonary blood flows and left ventricular function using implanted microprobes.

We have developed novel implantable Doppler microprobes to monitor beat-by-beat stroke volume and cardiac output (CO) after cardiac surgery. In 11 adults undergoing either coronary artery bypass grafting (n = 6) or valve replacement (n = 5), Doppler microprobes were implanted on the ascending aorta or the main pulmonary artery to measure aortic blood flow (ABF) or pulmonary artery blood flow (PBF). The diameters of both vessels were determined before surgery using two-dimensional echocardiography. Stroke volume was obtained from velocity tracings measured by a 4-MHz zero-crossing pulsed Doppler flowmeter. Simultaneous measurements of Doppler and thermodilution CO (TDCO) were compared. We found the following: ABF = 1.03 TDCO - 0.22 L/min (r = 0.89); while PBF = 0.69 TDCO - 1.24 L/min (r = 0.75). Furthermore, peak flow velocity and maximum acceleration of blood in the ascending aorta were measured after inotropic stimulation with dobutamine; both values increased significantly from control values (25.2 +/- 6.1 percent and 44.6 +/- 8.6 percent, respectively, at 7.5 micrograms/kg/min). We conclude that implanted aortic Doppler microprobes provide a sensitive and reliable method to measure aortic blood flow velocity after surgery and then allow monitoring of stroke volume and CO and analysis of left ventricular function after cardiac surgery.

Interactions between hemodynamic and hormonal modifications during PEEP-induced antidiuresis and antinatriuresis.

The interactions between hemodynamic and hormonal modifications during antidiuresis and antinatriuresis induced by positive end-expiratory pressure (PEEP) were studied in six patients under 15 cm H2O PEEP before PEEP and after the addition of lower body positive pressure (LBPP) to PEEP (PEEP+LBPP). We measured or calculated the following: cardiac index, systemic arterial, right atrial, pulmonary arterial, and pulmonary artery occlusive pressures; indexed renal blood flow (iodohippurate 131 sodium clearance); total blood volume (chromium 51 radiolabeled RBCs); glomerular filtration rate; urinary output; fractional excretion of sodium (FE Na+); plasma concentrations of antidiuretic hormone (ADH), plasma renin activity (PRA), norepinephrine and epinephrine; urinary concentration of PGE2 (PGE2u). Although LBPP application corrected PEEP deleterious effects on systemic and renal hemodynamics, sustained fall in Vu and in FE Na+ were observed. Antidiuresis was not due to ADH release. Sympathetic activation and high PRA appeared the main determinants of renal function alterations in PEEP ventilation.

Hypoxemia in acute pulmonary embolism.

Most patients with severe, acute pulmonary embolism (PE) have arterial hypoxemia. To further define the respective roles of ventilation to perfusion (VA/Q) mismatch and intrapulmonary shunt in the mechanism of hypoxemia, we used both right heart catheterization and the six inert gas elimination technique in seven patients with severe, acute PE (mean vascular obstruction, 55 percent) and hypoxemia (mean PaO2, 67 +/- 11 mm Hg). None had previous cardiopulmonary disease, and all were studied within the first ten days of initial symptoms. Increased calculated venous admixture (mean QVA/QT 16.6 +/- 5.1 percent) was present in all patients. The relative contributions of VA/Q mismatching and shunt to this venous admixture varied, however, according to pulmonary radiographic abnormalities and the time elapsed from initial symptoms to the gas exchange study. Although all patients had some degree of VA/Q mismatch, the two patients studied early (ie, less than 48 hours following acute PE) had normal chest x-ray film findings and no significant shunt; VA/Q mismatching accounted for most of the hypoxemia. In the others a shunt (3 to 17 percent of cardiac output) was recorded along with radiographic evidence of atelectasis or infiltrates and accounted for most of the venous admixture in one. In all patients, a low mixed venous oxygen tension (27 +/- 5 mm Hg) additionally contributed to the hypoxemia. Our findings suggest that the initial hypoxemia of acute PE is caused by an altered distribution of ventilation to perfusion. Intrapulmonary shunting contributes significantly to hypoxemia only when atelectasis or another cause of lung volume loss develops.

Decreased mesenteric blood flow supplying retrosternal esophageal ileocoloplastic grafts during positive-pressure breathing.

Esophageal replacement after esophagogastric injury caused by ingestion of lye may require the interposition of a retrosternal ileocolic graft. In this new anatomic situation, the mesenteric circulation supplying the graft is subjected to the intrathoracic pressure surrounding the graft. Thus, mesenteric blood flow supplying the graft may be impaired when intrathoracic pressure is increased during mechanical ventilation. This study was designed to evaluate the effect of increasing intrathoracic pressure by application of a positive end-expiratory pressure on mesenteric blood flow supplying esophageal ileocolic grafts. Eight cases were studied in the immediate postoperative period. Miniaturized implantable Doppler microprobes were sutured to the single artery supplying the graft and connected to an 8 MHz pulsed Doppler flowmeter. Two sets of measurements were successively performed with zero end-expiratory pressure ventilation and after application of a 15 cm water positive end-expiratory pressure. Positive end-expiratory pressure induces mean arterial pressure (-12%); p < 0.05) and cardiac output (-17%; p < 0.05) decrease. Mesenteric blood flow also decreases (-38%; p < 0.05) as did the mesenteric blood flow/cardiac output ratio, suggesting a potential mesenteric vasoconstriction assessed by mesenteric vascular resistance increase and mesenteric diastolic blood flow velocity decrease. These results suggest that, in the particular anatomic situation of the graft, increased intrathoracic pressure induces mesenteric blood flow decrease in relation to systemic hemodynamic alterations associated with perivisceral pressure increase. This change may be deleterious to graft perfusion.