The effect of normal saline resuscitation on vital organ blood flow in septic sheep

Objective To study the effect of resuscitation with normal saline on vital organ blood flow and renal function in sepsis.Design and setting Randomized controlled cross-over animal study in the animal laboratory of university physiology institute.Subjects Six merino cross-ewes.Interventions Chronic implantation of flow probes around aorta, coronary, renal and mesenteric arteries. Intravenous administration of live Escherichia coli. Random allocation to normal saline resuscitation (20 ml/kg over 15 min) or observation (control) for 210 min. Continuous measurement of central haemodynamics, organ blood flow and renal function.Results Live E. coli induced hyperdynamic sepsis with oliguria (28.3 ± 12.6 to 16.7 ± 11.9 ml/30min) and reduced creatinine clearance (87.9 ± 24.5 to 44.3 ± 34.5 ml/min). During this septic state mesenteric, coronary and renal blood flow increased. During the first hour (early effect) after saline resuscitation, central venous pressure, cardiac output, stroke volume, coronary blood flow, mesenteric blood flow, urine output and creatinine clearance increased, but there was no change in renal blood flow. In the following 2 h these increments were significantly attenuated, but urine output and creatinine clearance remained greater than controls; renal blood flow decreased slightly and the fractional excretion of sodium increased significantly.Conclusion In hyperdynamic sepsis resuscitation with normal saline increases central venous pressure, cardiac output, mesenteric blood flow, urine output, creatinine clearance, and fractional excretion of sodium despite a lack of effect on renal blood flow. These effects, however, are transient.     

Vasopressin or norepinephrine in early hyperdynamic septic shock: a randomized clinical trial

Objective To compare the effects of arginine-vasopressin (AVP) and norepinephrine (NE) on hemodynamic variables, organ dysfunction, and adverse events in early hyperdynamic septic shock.Design and setting Randomized, controlled, open-label trial.Patients and participants Twenty-three patients with early (12 h) hyperdynamic septic shock in two teaching hospitals.Interventions AVP (0.04–0.20 U min^–1, n = 13) as a single agent or NE (0.1–2.8 μg kg^–1 min^–1, n = 10) infusion for 48 h to achieve mean arterial pressure at or above 70 mmHg.Measurements and results Hemodynamic parameters and Sequential Organ Failure Assessment (SOFA) score were measured. AVP and NE equally increased mean arterial pressure over 48 h, but NE was required in 36% of AVP patients at 48 h. Compared to baseline, AVP increased systemic vascular resistance, decreased exposure to NE, decreased cardiac output by decreasing heart rate, increased creatinine clearance, and improved SOFA score. The PrCO₂ – PaCO₂ difference remained stable throughout the study. One AVP patient developed acute coronary syndrome with dose-dependent ECG changes. Three patients in both groups died during their ICU stay.Conclusion In early hyperdynamic septic shock, the administration of high-dose AVP as a single agent fails to increase mean arterial pressure in the first hour but maintains it above 70 mmHg in two-thirds of patients at 48 h. AVP decreases NE exposure, has no effect on the PrCO₂ – PaCO₂ difference, and improves renal function and SOFA score.This work was supported by the Cardiovascular Critical Care research Network FRSQ and departmental funding.     

Terlipressin as a rescue therapy for catecholamine-resistant septic shock in children

Objective To evaluate the effect of terlipressin on oxygenation, PaO₂/FIO₂, heart rate, mean arterial pressure, and mortality in children with septic shock refractory to high doses of dopamine/dobutamine and adrenaline. Design and setting A randomized, nonblind study in the pediatric intensive care unit of a university hospital. Patients and measurements We studied 58 children with septic shock and refractory hypotension despite fluid loading and high doses of catecholamines, randomly enrolled to terlipressin (TP, n = 30) or control (n = 28). TP was administered as intravenous bolus doses of 20 μg/kg every 6 h for a maximum of 96 h. Hemodynamic changes, PaO₂/FIO₂ rates, length of stay, and mortality rate in PICU were recorded prospectively. Results Mean arterial pressure and PaO₂/FIO₂ significantly increased, and heart rate significantly decreased 30 min after each TP treatment, but mortality did not differ from control (67.3% vs. 71.4%). Mean stay in the PICU was shorter in the TP group (13.4 ± 7.9 vs. 20.2 ± 9.7 days and was longer among nonsurvivors of the TP group vs. control (10.4 ± 6.9 vs. 6.2 ± 3.4 days). Blood urea nitrogen, creatinine, AST, ALT, and urine output of patients in the TP group did not change after terlipressin. Conclusions Although terlipressin infusion had no effect on mortality, it significantly increases mean arterial pressure, PaO₂/FIO₂, and survival time in nonsurvivors. Terlipressin seems to cause no adverse effect but warrants further evaluation as a rescue therapy in refractory septic shock.     

Renal arterial resistance in septic shock: effects of increasing mean arterial pressure with norepinephrine on the renal resistive index assessed with Doppler ultrasonography

Objective To determine the effects of increasing mean arterial pressure (MAP) on renal resistances assessed by Doppler ultrasonography in septic shock. Design and setting Prospective, single-center, nonrandomized, open-label trial in the surgical intensive care unit in a university teaching hospital. Patients and participants 11 patients with septic shock who required fluid resuscitation and norepinephrine to increase and maintain MAP at or above 65 mmHg. Interventions Norepinephrine was titrated in 11 patients in septic shock during three consecutive not randomized periods of 2 h to achieve a MAP at successively 65, 75, and 85 mmHg. Measurements and results At the end of each period hemodynamic parameters and renal function variables (urinary output, creatinine, clearance) were measured, and Doppler ultrasonography was performed on interlobar arteries to assess the renal resistive index. When increasing MAP from 65 to 75 mmHg, urinary output increased significantly from 76 ± 64 to 93 ± 68 ml/h and the resistive index significantly decreased from 0.75 ± 0.07 to 0.71 ± 0.06. No difference was found between 75 and 85 mmHg. Conclusions Doppler ultrasonography and resistive index measurements may help determine in each patient the optimal MAP for renal blood flow and may be a relevant end-point to titrate the hemodynamic treatment in septic shock.     

Replacement of 24-h creatinine clearance by 2-h creatinine clearance in intensive care unit patients: a single-center study

Objective To estimate the usefulness of 2-h creatinine clearance (CrCl) in the ICU and define variables that may reduce agreement. Design Prospective study. Setting Polyvalent ICU of a university hospital. Patients 359 patients. Interventions We compared 24-h CrCl (CrCl-24h), as the standard measure, with 2-h CrCl (CrCl-2h) (at the start of the period) and the Cockroft–Gault equation (Ck-G). Measurements and results The 2-h sample was lost in two patients (0.6%) and the 24-h sample was lost in 50 patients (13.9%). The mean Ck-G was 87.4 ± 3.05, with CrCl-2h 109.2 ± 4.46 and CrCl-24h 100.9 ± 4.21 ml/min/1.73 m² (r ² of 0.88 for CrCl-2h and 0.84 for Ck-G). The differences from ClCr-24h were 21.8 ± 3.3 ( p < 0.001) for the Ck-G and 8.3 ± 2.6 ( p < 0.05) for CrCl-2h ( p < 0.05). In the subgroup of patients with CrCl-24h < 100 ml/min/1.73 m², the CrCl-24h value was 52.9 ± 2.71 vs. 51.6 ± 2.14 for CrCl-2h ( p = ns) and 57.6 ± 2.56 ( p < 0.001) for the Ck-G. Patients with CrCl < 100 ml/min only showed variability in hyperglycemia during the 24-h period. Conclusions In intensive care patients, 24-h CrCl results in a large proportion of non-valid determinations, even under conditions of close monitoring. Two-hour CrCl is an adequate substitute, even in patients who are unstable or who have irregular diuresis where a 24-h collection is impossible. The Cockroft–Gault equation seems less useful in this setting. All the authors participated actively in the present study. This is an original paper that has not been submitted for publication elsewhere, though partial results of the study were presented at the Annual Congress of the ESICM in Amsterdam (September 2005), and the final results were presented at the Annual Congress of the SEMICYUC (Pamplona, 2006). The authors received no external financing for conduct of the study, and there are no conflicts of interest for any of them. This article is discussed in the editorial available at: .     

Short-term beneficial effects of methylene blue on kidney damage in septic shock patients

Objective We previously demonstrated that upregulation of renal inducible nitric oxide synthase (iNOS) is associated with proximal tubule injury during systemic inflammation in humans. In this study we investigated the short-term effect of methylene blue (MB), an inhibitor of the NO pathway, on kidney damage and function in septic shock patients. Design and setting A prospective clinical study conducted in an intensive care unit. Patients Nine patients (four men, five women, mean age 71 ± 3 years) with confirmed or suspected bacterial infection and with refractory septic shock defined as a mean arterial pressure ≤ 70 mmHg despite norepinephrine infusion ≥ 0.2 μg/kg per minute. Interventions A 4 h continuous intravenous infusion of 1 mg/kg MB per hour. Measurements and results The urinary excretion of NO metabolites decreased with median 90% (range 75–95%) from baseline to 6 h after MB administration. The first 24 h creatinine clearance improved by 51% (18–173%) after MB treatment but was still strongly impaired. During the first 6 h after the start of MB treatment both the urinary excretion of cytosolic glutathione S-transferase A1-1 and P1-1, markers for proximal and distal tubule damage, respectively, decreased by 45% (10–70%) and 70% (40–85) vs. baseline. After termination of the MB infusion the NO metabolites and markers of tubular injury returned to pretreatment levels. Conclusions In septic patients with refractory shock short-term infusion of MB is associated with a decrease in NO production and an attenuation of the urinary excretion of renal tubular injury markers. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. S. H. was supported by a grant from The Netherlands Organization for Scientific Research; F. v. H. was supported by a grant from the Waikato Medical Research Foundation; P. P. is recipient of a Clinical Fellowship grant of The Netherlands Organization for Scientific Research.     

The effect of exogenous surfactant in patients with lung contusions and acute lung injury

Objective To investigate the acute effect of surfactant replacement in multiple-trauma patients with lung contusion and acute lung injury. Design and setting Prospective randomized clinical trial in the 14-bed ICU of a 750-bed university hospital. Patients and participants Sixteen ventilated trauma patients with severe refractory hypoxemia (PaO₂/FIO₂ < 150 mmHg) and lung contusions. Interventions Patients were randomly assigned to either surfactant administration (n = 8) or standard treatment (n = 8). A single dose of natural bovine surfactant was instilled bronchoscopically in the involved lung areas; each segmental bronchus received (200/19) mg/kg body weight. Measurements and results The surfactant group demonstrated an acute improvement in oxygenation after surfactant replacement compared both to control group and to baseline values. In the surfactant group PaO₂/FIO₂ increased from 100 ± 20 mmHg at baseline to 140 ± 20 (6 h), 163 ± 26 (12 h), and 187 ± 30 mmHg (24 h). Compliance increased from 30 to 36 ml/cmH₂O at 6 h after administration, and this increase remained significant at the 24, 48, and 72 h time points. The surfactant group demonstrated a higher response to recruitment maneuvers than the control group at 6 h. The mean duration of ventilatory support was 5.6 ± 2.6 days in the surfactant group and 8.1 ± 2.4 days in the control group. Conclusions Surfactant replacement was well tolerated in patients with lung contusions and severe hypoxemia and resulted in improved oxygenation and compliance.     

Urinary biomarker of oxidative stress correlating with outcome in critically septic patients

Objective To determine whether urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), an in vivo parameter of oxidative stress, is correlated with the outcome of critically septic patients. Design and setting Clinical outcome study in an adult medical ICU. Patients Eighty-five consecutive septic patients: 59 men and 26 women. Measurements and results Urinary 8-OHdG was analyzed using isotope-dilution liquid chromatography with tandem mass spectrometry (LC/MS/MS). ICU mortality in these 85 septic patients was 25.9% (n = 22) and hospital mortality 38.8% (n = 33). APACHE II scores of survivors on day 1, on day 3, and the difference between them differed significantly from those of nonsurvivors (day 1, 21.0 ± 7.1 vs. 25.9 ± 8.0; day 3, 15.0 ± 5.8 vs. 23.2 ± 8.3; difference, 6.0 ± 5.5 vs. 1.7 ± 6.6). Urinary 8-OHdG was significantly lower in survivors than in nonsurvivors on day 1 (1.8 ± 2.4 vs. 3.0 ± 2.4). The area under receiver operating characteristic curve analysis for the association between day 1 urinary 8-OHdG and ICU mortality was 0.71. The comparison performed upon discharge from hospital revealed similar results. Conclusions This is a preliminary study. The excretion of the urinary 8-OHdG, as measured using isotope-dilution LC/MS/MS, as the APACHE II score, were correlated with the outcome of critically septic patients in medical ICU. An erratum to this article can be found at     

Spontaneous breathing during airway pressure release ventilation in experimental lung injury: effects on hepatic blood flow

Objective Positive pressure ventilation can affect systemic haemodynamics and regional blood flow distribution with negative effects on hepatic blood flow. We hypothesized that spontaneous breathing (SB) with airway pressure release ventilation (APRV) provides better systemic and hepatic blood flow than APRV without SB. Design Animal study with a randomized cross-over design. Setting Animal laboratory of Bonn University Hospital. Subjects Twelve pigs with oleic-acid-induced lung injury. Interventions APRV with or without SB in random order. Without SB, either the upper airway pressure limit or the ventilator rate was increased to maintain constant pH and PaCO₂. Measurements and results Systemic haemodynamics were determined by double-indicator dilution, organ blood flow by coloured microspheres. Systemic blood flow was best during APRV with SB. During APRV with SB blood flow (ml g⁻¹ min⁻¹) was 0.91 ± 0.26 (hepatic arterial), 0.29 ± 0.05 (stomach), 0.64 ± 0.08 (duodenum), 0.62 ± 0.10 (jejunum), 0.53 ± 0.07 (ileum), 0.53 ± 0.07 (colon), 0.46 ± 0.09 (pancreas) and 3.59 ± 0.55 (spleen). During APRV without SB applying high P_aw it decreased to 0.13 ± 0.01 (stomach), 0.37 ± 0.03 (duodenum), 0.29 ± 0.03 (jejunum), 0.31 ± 0.05 (ileum), 0.32 ± 0.03 (colon) and 0.23 ± 0.04 (pancreas) p < 0.01, respectively. During APRV without SB applying same P_aw limits it decreased to 0.18 ± 0.03 (stomach, p < 0.01), 0.47 ± 0.06 (duodenum, p < 0.05), 0.38 ± 0.05 (jejunum, p < 0.01), 0.36 ± 0.03 (ileum, p < 0.05), 0.39 ± 0.05 (colon, p < 0.05), and 0.27 ± 0.04 (pancreas, p < 0.01). Arterial liver blood flow did not change significantly when SB was abolished (0.55 ± 0.11 and 0.63 ± 0.11, respectively). Conclusions Maintaining SB during APRV was associated with better systemic and pre-portal organ blood flow. Improvement in hepatic arterial blood flow was not significant. This article is discussed in the editorial available at: .     

Increased colorectal permeability in patients with severe sepsis and septic shock

Objective To develop a method for the assessment of colorectal permeability in septic patients.Design and setting Observational study in ICUs at two university hospitals.Participants Nine patients with septic shock and abdominal focus of infection, 7 with severe sepsis and pulmonary focus and 8 healthy subjects.Measurements and results Colorectal permeability was assessed as the initial appearance rate of ^99mTc-DTPA in plasma after instillation into the rectal lumen and as the cumulative systemic recovery at 1 h. To calculate the latter, volume of distribution and renal clearance of ^99mTc-DTPA was estimated by an i. v. bolus of ⁵¹Cr-EDTA. The initial rate of permeability was increased in patients with septic shock and severe sepsis compared with controls [29.0 (3.7–83.3), 20.6 (3.6–65.5) and 6.0 (2.2–9.6) cpm ml⁻¹ min⁻¹, respectively, p < 0.05)] with a positive linear trend (r ² = 0.27, p = 0.01) and correlated to L-lactate concentrations in the rectal lumen (r ² = 0.39, p < 0.05). The cumulative permeability was also increased in patients with septic shock and severe sepsis compared with controls [2.07 (0.05–15.7), 0.32 (0.01–1.2) and 0.03 (0.01–0.06)‰, respectively, p < 0.01] and correlated to the initial permeability rate (r ² = 0.26, p = 0.01).Conclusions In septic patients, the systemic recovery of a luminally applied marker of paracellular permeability was increased and related to the luminal concentrations of L-lactate and possibly to disease severity. This suggests that the assessment of colorectal permeability by systemic recovery of ^99mTc-DTPA is valid and that metabolic dysfunction of the mucosa contributes to increased permeability of the large bowel in patients with severe sepsis and septic shock.     

Is myocardial adrenergic responsiveness depressed in human septic shock?

Objective To assess left ventricular (LV) contractile function and adrenergic responsiveness in septic patients. Methods We used echocardiographically defined fractional area of contraction (FAC), and LV area to end-systolic arterial pressure estimates of end-systolic elastance (E'es) and its change in response to dobutamine (5 μg/kg/min) in 10 subjects in septic shock admitted to an intensive care unit of an academic medical center. Subjects were studied on admission and again at both 5 days and 8–10 days after admission. Results Three of the 10 subjects died as a result of their acute process, while the others were discharged from hospital. Nine out of 10 subjects required intravenous vasopressor therapy on day 1, while only 1 of 9 subjects required vasopressor support at day 5. LV end-diastolic area (EDA) increased from day 1 to day 5 and days 8–10 (p < 0.05), but neither FAC nor E'es was altered by time (EDA 15.7 ± 5.8, 21.4 ± 5.1, and 19.4 ± 5.6 cm²; FAC 0.46 ± 0.19, 0.50 ± 0.20, and 0.48 ± 0.15%; E'es 21.6 ± 12.6, 23.2 ± 8.5, and 19.2 ± 6.3 mmHg/cm², mean ± SD, for days 1, 5 and 8–10 respectively). Although dobutamine did not alter E'es on day 1 or day 5, E'es increased in all of the 5 subjects studied on days 8–10 (p < 0.05). Conclusions Adrenergic hyporesponsiveness is present in septic shock and persists for at least 5 days into recovery, resolving by days 8–10 in survivors. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Dr. Pinsky was a Professeur Associé at Cochin Hospital and Paris Descartes University.     

Urinary biomarkers in septic acute kidney injury

Objective To appraise the literature on the value of urinary biomarkers in septic acute kidney injury (AKI). Design Systematic review. Setting Academic medical centre. Patients and participants Human studies of urinary biomarkers. Interventions None. Measurements and results Fourteen articles fulfilled inclusion criteria. Most studies were small, single-centre, and included mixed medical/surgical adult populations. Few focused solely on septic AKI and all had notable limitations. Retrieved articles included data on low-molecular-weight proteins (β₂-microglobulin, α₁-microglobulin, adenosine deaminase binding protein, retinol binding protein, cystatin C, renal tubular epithelial antigen-1), enzymes (N-acetyl-β-glucosaminidase, alanine-aminopeptidase, alkaline phosphatase; lactate dehydrogenase, α/π-glutathione-S-transferase, γ-glutamyl transpeptidase), cytokines [platelet activating factor (PAF), interleukin-18 (IL-18)] and other biomarkers [kidney injury molecule-1, Na/H exchanger isoform-3 (NHE3)]. Increased PAF, IL-18, and NHE3 were detected early in septic AKI and preceded overt kidney failure. Several additional biomarkers were evident early in AKI; however, their diagnostic value in sepsis remains unknown. In one study, IL-18 excretion was higher in septic than in non-septic AKI. IL-18 also predicted deterioration in kidney function, with increased values preceding clinically significant kidney failure by 24–48 h. Detection of cystatin C, α₁-microglobulin, and IL-18 predicted need for renal replacement therapy (RRT). Conclusions Few clinical studies of urinary biomarkers in AKI have included septic patients. However, there is promising evidence that selected biomarkers may aid in the early detection of AKI in sepsis and may have value for predicting subsequent deterioration in kidney function. Additional prospective studies are needed to accurately describe their diagnostic and prognostic value in septic AKI.     

Effects of levosimendan and dobutamine in experimental acute endotoxemia: a preliminary controlled study

Objective To test the hypothesis that levosimendan increases systemic and intestinal oxygen delivery (DO₂) and prevents intramucosal acidosis in septic shock. Design Prospective, controlled experimental study. Setting University-based research laboratory. Subjects Nineteen anesthetized, mechanically ventilated sheep. Interventions Endotoxin-treated sheep were randomly assigned to three groups: control (n = 7), dobutamine (10 μg/kg/min, n = 6) and levosimendan (100 μg/kg over 10 min followed by 100 μg/kg/h, n = 6) and treated for 120 min. Measurements and main results After endotoxin administration, systemic and intestinal DO₂ decreased (24.6 ± 5.2 vs 15.3 ± 3.4 ml/kg/min and 105.0 ± 28.1 vs 55.8 ± 25.9 ml/kg/min, respectively; p < 0.05 for both). Arterial lactate and the intramucosal–arterial PCO₂ difference (ΔPCO₂) increased (1.4 ± 0.3 vs 3.1 ± 1.5 mmHg and 9 ± 6 vs 23 ± 6 mmHg mmol/l, respectively; p < 0.05). Systemic DO₂ was preserved in the dobutamine-treated group (22.3 ± 4.7 vs 26.8 ± 7.0 ml/min/kg, p = NS) but intestinal DO₂ decreased (98.9 ± 0.2 vs 68.0 ± 22.9 ml/min/kg, p < 0.05) and ΔPCO₂ increased (12 ± 5 vs 25 ± 11 mmHg, p < 0.05). The administration of levosimendan prevented declines in systemic and intestinal DO₂ (25.1 ± 3.0 vs 24.0 ± 6.3 ml/min/kg and 111.1 ± 18.0 vs 98.2 ± 23.1 ml/min/kg, p = NS for both) or increases in ΔPCO₂ (7 ± 7 vs 10 ± 8, p = NS). Arterial lactate increased in both the dobutamine and levosimendan groups (1.6 ± 0.3 vs 2.5 ± 0.7 and 1.4 ± 0.4 vs. 2.9 ± 1.1 mmol/l, p = NS between groups). Conclusions Compared with dobutamine, levosimendan increased intestinal blood flow and diminished intramucosal acidosis in this experimental model of sepsis. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. This study was solely funded by the Cátedra de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de La Plata. None of the authors have any financial interests to disclose. This article is discussed in the editorial available at: .     

Should dialysis be offered to cancer patients with acute kidney injury?

Objectives Cancer patients are at high risk for acute kidney injury (AKI), which is associated with high mortality when renal replacement therapy is required. Because physicians might be reluctant to offer dialysis to patients with malignancies, we sought to appraise outcomes in critically ill cancer patients (mainly with hematological malignancies) who received renal replacement therapy for AKI complicating cancer management. Design Cohort study including consecutive patients who received renal replacement therapy for AKI complicating cancer management, over a 42-month period. Their mortality was compared with that of non-cancer patients who received renal replacement therapy in the same center over the same study period (control group). Setting A 12-bed medical intensive care unit in a university hospital. Results 94 critically-ill cancer patients met the inclusion criteria. Median SAPS II was 53 (IQR 40–75) and median Logistic Organ Dysfunction score was 7 (IQR 5–10). The etiology of AKI was multiple in most patients (248 identified factors in 93 patients). Hospital mortality was 51.1%. Two variables were independently associated with hospital mortality: the severity of associated organ failures at ICU admission (OR, 1.33; 95% CI, 1.11–1.59; per point) and renal function deterioration after ICU admission (OR, 5.42; 95% CI, 1.62–18.11). Characteristics of the malignancy were not associated with hospital mortality. The presence of cancer had no detectable influence on hospital mortality after adjustment for gender, age, acute severity as assessed by the SAPS II score, and chronic health status [OR 1.2, 95% CI 0.63–2.27; p = 0.57]. Conclusion ICU admission should be considered in selected critically ill cancer patients with AKI requiring renal replacement therapy.     

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 (Δ) 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 μg/dl), but the response to corticotropin test did not differ between these two subgroups. ROC analysis showed threshold values for t ₀ (32 μg/dl) and Δ (8 μg/dl) that best discriminated survivorsfrom 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, Δ, or both. In addition, adrenal function testsand 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.     

Ionic dialysance: a new valid parameter for quantification of dialysis efficiency in acute renal failure?

Objective Several studies have reported a close relationship between an increased dose of dialysis and survival in patients treated for acute renal failure. Unfortunately, the quantification of dialysis in critically ill patients based on the urea nitrogen formula Kt/V is not applicable. Ionic dialysance is a new parameter calculated in real time from the dialysate conductivity and correlated with the effective urea clearance in chronic hemodialysis patients. The aim of our study was to evaluate ionic dialysance in the quantification of dialysis in critically ill patients with acute renal failure. Design Prospective open-label study. Setting An 18-bed medical intensive care unit. Patients Thirty-one patients with multiple organ dysfunction syndrome and acute renal failure requiring intermittenthemodialysis were included. Measurements Using the first dialysis session of each patient, we compared the delivered dose of dialysis based on ionic dialysance measurement (Kt_ID) with the well-accepted gold standard method based on fractional dialysate sampling (Kt_dialysate). The data were analyzed using linear regression and Bland–Altman analysis. Results Thirty-one intermittent hemodialysis sessions were performed in 31 critically ill patients (mean age 58 ± 12 years, SAPS II score 56 ± 10). We found a close correlation between Kt_dialysate and Kt_ID (Kt_dialysate = 36.3 ± 11.4 l; Kt_ID = 38.4 ± 11.8; r = 0.96) with excellent limits of agreement (–2.2 l; 6.4 l). Conclusion The feasibility of dialysis quantification based on ionic dialysance in the critically ill patient is good. This method is a simple and accurate tool for the determination of dialysis dose in critically ill patients.     

Effects of vertical positioning on gas exchange and lung volumes in acute respiratory distress syndrome

Objective Supine position may contribute to the loss of aerated lung volume in patients with acute respiratory distress syndrome (ARDS). We hypothesized that verticalization increases lung volume and improves gas exchange by reducing the pressure surrounding lung bases.Design and setting Prospective observational physiological study in a medical ICU.Subjects and intervention In 16 patients with ARDS we measured arterial blood gases, pressure-volume curves of the respiratory system recorded from positive-end expiratory pressure (PEEP), and changes in lung volume in supine and vertical positions (trunk elevated at 45° and legs down at 45°).Measurements and results Vertical positioning increased PaO₂ significantly from 94 ± 33 to 142 ± 49 mmHg, with an increase higher than 40% in 11 responders. The volume at 20 cmH₂O measured on the PV curve from PEEP increased using the vertical position only in responders (233 ± 146 vs. –8 ± 91 ml in nonresponders); this change was correlated to oxygenation change (ρ = 0.55). End-expiratory lung volume variation from supine to vertical and 1 h later back to supine, measured in 12 patients showed a significant increase during the 1-h upright period in responders (n = 7) but not in nonresponders (n = 5; 215 ± 220 vs. 10 ± 22 ml), suggesting a time-dependent recruitment.Conclusions Vertical positioning is a simple technique that may improve oxygenation and lung recruitment in ARDS patients.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

Urinary biomarker of oxidative stress correlating with outcome in critically septic patients

Objective To determine whether urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), an in vivo parameter of oxidative stress, is correlated with the outcome of critically septic patients. Design and setting Clinical outcome study in an adult medical intensive care unit (ICU). Patients 85 consecutive septic patients (59 men, 26 women). Measurements and results Patient characteristics and the clinical course were examined. Urinary 8-OHdG was analyzed using isotope-dilution liquid chromatography with tandem mass spectrometry (LC/MS/MS). ICU mortality was 25.9% (22/85) and hospital mortality 38.8% (33/85). Survivors' APACHE II scores on days 1 and 3 and the difference between them differed significantly from those of nonsurvivors (day 1, 21.0 ± 7.1 vs. 25.9 ± 8.0; day 3, 15.0 ± 5.8 vs. 23.2 ± 8.3; difference, 6.0 ± 5.5 vs. 1.7 ± 6.6). Urinary 8-OHdG was significantly lower in survivors than in nonsurvivors on day 1 (1.8 ± 2.4 vs. 3.0 ± 2.4). The area under receiver operating characteristic curve analysis for the association between day 1 urinary 8-OHdG and ICU mortality was 0.71. The comparison performed upon discharge from hospital revealed similar results. Conclusions This is a preliminary study. Excretion of urinary 8-OHdG, as measured using isotope-dilution LC/MS/MS, and the APACHE II score were correlated with the outcome of critically septic patients in medical ICU.     

Incidence, risk factors and prognosis of changes in serum creatinine early after aortic abdominal surgery

Objective To determine the incidence, risk factors, and prognostic implications of serum creatinine changes following major vascular surgery.Design Observational study.Settings University hospital.Patients Cohort of 599 consecutive patients undergoing elective abdominal aortic surgery.Interventions Review of prospectively collected data from 1993 to 2004.Measurements and results The receiver-operator characteristic (ROC) curve analysis was used to detect the best threshold for postoperative elevation in serum creatinine (Δ Creat) in relation to major complications. A cut-off value of +0.5 mg/dl was selected to define renal dysfunction (RD_0.5 group, n = 91; no RD_0.5, n = 508) that was associated with higher mortality (7.7% in RD_0.5 group vs 1.4% in no RD_0.5 group, P < 0.05), rate of admission to the ICU (34% vs 13%, P < 0.05), and incidence of cardiovascular (9% vs 4%, P < 0.05), respiratory (21% vs 7%, P < 0.05), surgical (24% vs 10%, P < 0.05), and septic complications (9% vs 3%, P < 0.05). After multivariate analysis with logistic regression, renal dysfunction was independently related to low preoperative creatinine clearance [< 40 ml/min; odds ratio (OR) 1.5, 95% confidence interval (CI) 1.1–3.9], prolonged renal ischemic time (> 40 min; OR, 3.8, 95% CI, 1.9–7.2), blood transfusion (> 5 units; OR, 1.9, 95% CI 1.2–6.1), and rhabdomyolysis (OR, 3.6, 95% CI 1.7–7.9). Conclusions Postoperative RD_0.5 (Δ Creat  > 0.5 mg/dl) occurs in 15% of vascular patients and carries a bad prognosis. Preoperative renal insufficiency and factors related to the complexity of surgery are the main predictors of renal dysfunction.     

Emergency endovascular stent graft repair for acute blunt thoracic aortic injury: a retrospective case control study

Objective To compare surgical and endovascular stent graft (ESG) treatment of blunt thoracic aortic injury (BAI) in the emergency setting.Design and setting Retrospective case control study in two surgical intensive care units of a university hospital.Patients 30 patients who presented with BAI between 1995 and 2005: 17 treated surgically and 13 by ESG. The two groups were comparable for the severity of trauma and mean delay before treatment; the mean age was higher in the ESG group (46 ± 18 vs. 35 ± 15 years).Results In the surgical group time spent in the operating theater was longer (310 ± 130 vs. 140 ± 48 min) and blood losses higher (2000 ± 1300 vs. no significant bleeding); aortic clamping time was 48 ± 20 min. The mortality rate was 15% with ESG (n = 2) and 23% with surgery (n = 4). Complications of the procedure were more frequent in the surgical group (1 vs. 7). In the ESG group there was one pulmonary embolism. In the surgical group there were three neurological complications, one acute aortic dissection, one perioperative rupture, one periprosthetic leak, and one septic shock. Two complications (postoperative aortic dissection and paraplegia) appeared in the same patient in the surgical group. Intensive care unit length of stay, duration of mechanical ventilation, and catecholamine support were similar in the two groups.Conclusions Stent graft for emergency treatment of BAI is efficient and is associated with fewer complications than surgical treatment.