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: .     

Treatment of severe acute respiratory distress syndrome: role of extracorporeal gas exchange

Objective To evaluate the effect of extracorporeal gas exchange (ECMO) on mortality of patients referred with severe acute respiratory distress syndrome (ARDS).Design and setting Prospective observational study in a university hospital ICU.Patients 150 patients with severe ARDS.Interventions Multimodal treatment with and without ECMO.Measurements and main results We treated 118 patients (78.7%) conservatively and 32 patients with ECMO. Patients in the ECMO group presented with significantly more severe disease (lung injury score 3.8 ± 0.3 vs. 3.3 ± 0.4; SOFA score 52 ± 14 vs. 43 ± 12; and SAPS score 14 ± 3.3 vs. 10 ± 3.5). Mortality in ECMO-treated patients tended to be higher than that with conservative treatment (46.9% vs. 28.8%, p = 0.059). Multivariate logistic regression analyses with backward selection excluded ECMO as predictor of mortality (p = 0.79). Independent predictors of mortality were age (odds ratio 1.044, 95% confidence interval 1.014–1.075, p = 0.004), mean pulmonary artery pressure (1.082, 1.026–1.141, p = 0.036), sequential organ failure assessment score (1.148, 1.018–1.294, p = 0.024), and days of mechanical ventilation prior to referral (1.064, 1.008–1.123, p = 0.025).Conclusion ECMO treatment does not predict mortality in patients with most severe ARDS.     

Effect of activated protein C on pulmonary blood flow and cytokine production in experimental acute lung injury

Objective In acute lung injury (ALI) activated protein C (APC) may reopen occluded lung vessels and minimize lung inflammation. We aimed at assessing the effect of APC on regional lung perfusion, aerated lung volume, cytokine production and oxygenation in experimental ALI. Design and setting Prospective, controlled study in an imaging facility. Participants Pigs tracheotomized and mechanically ventilated. Intervention Pigs were randomly given intravenously APC (n = 8) or saline (n = 8). Thirty minutes later, ALI was induced by injecting oleic acid. Measurements and results Lung perfusion and aerated lung volume measured with positron emission tomography, plasma cytokines and arterial blood gas were determined just before ALI and 110 and 290 min thereafter. Lung cytokines were measured at the end of the experiment. PaO₂ under F_IO₂ 1 was significantly lower in the APC group before lung injury (473 ± 129 vs. 578 ± 54 mmHg) and 110 min (342 ± 138 vs. 446 ± 103 mmHg) and 290 min (303 ± 171 vs. 547 ± 54 mmHg) thereafter (p < 0.05). Lung perfusion nonsignificantly tended to redistribute towards dorsal lung regions with APC. Total aerated lung volume was not different between APC and control before ALI (10.0 ± 1.5 vs. 11.0 ± 2.5 ml/kg) (p > 0.05) or thereafter. Plasma IL-6 and IL-8 at 110 min were greater with APC (p < 0.05). Conclusions In contrast to studies using other models, pretreatment with APC was associated with worsening oxygenation in the present investigation. This might be due to ventilation–perfusion mismatch, with more perfusion to dependent nonaerated areas. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. This article is discussed in the editorial available at: .     

Excess ICU mortality attributable to ventilator-associated pneumonia: The role of early vs late onset

Objective To determine the impact of ventilator-associated pneumonia (VAP) on ICU mortality, and whether it is related to time of onset of pneumonia. Design Prospective cohort study. Setting 16-bed medical-surgical ICU at a university-affiliated hospital. Patients and measurements From 2002 to 2003, we recorded patients receiving mechanical ventilation for > 72 h. Patients developing an infection other than VAP were excluded. Patients definitively diagnosed with VAP (n = 40) were cases and patients free of any infection acquired during ICU stay (n = 61) were controls. The VAP-attributed mortality was defined as the difference between observed mortality and predicted mortality (SAPS II) on admission. Results Mechanical ventilation was longer in VAP patients (25 ± 20 vs 11 ± 9 days; p < 0.001), as was ICU stay (33 ± 23 vs 14 ± 12 days; p < 0.001). In the non-VAP group, no difference was found between observed and predicted mortality (27.9 vs 27.4%; p > 0.2). In the VAP group, observed mortality was 45% and predicted mortality 26.5% (p < 0.001), with attributable mortality 18.5%, and relative risk (RR) 1.7 (95% CI 1.12–23.17). No difference was observed between observed and predicted mortality in early-onset VAP (27.3 vs 25.8%; p > 0.20); in late-onset VAP, observed mortality was higher (51.7 vs 26.7%; p < 0.01) with attributable mortality of 25% and an RR 1.9 (95% CI 1.26–2.63). Empiric antibiotic treatment was appropriate in 77.5% of episodes. No differences in mortality were related to treatment appropriateness. Conclusions In mechanically ventilated patients, VAP is associated with excess mortality, mostly restricted to late-onset VAP and despite appropriate antibiotic treatment.     

De-escalation therapy rates are significantly higher by bronchoalveolar lavage than by tracheal aspirate

Objective To assess outcomes with de-escalation therapy in ventilator-associated pneumonia (VAP). Design Prospective observational study. Setting Multidisciplinary intensive care unit. Patients and participants VAP was diagnosed by positive quantitative cultures of both tracheal aspirate and bronchoalveolar lavage (BAL) and treated appropriately for all significant isolates of tracheal aspirate and BAL in 143 patients who were assigned to de-escalation therapy by BAL or tracheal aspirate. Interventions None. Measurements and results Antibiotic therapy was de-escalated in 58 patients (40.5%), who had decreased mortality at day 15 (5.1% vs. 31.7%) and day 28 (12% vs. 43.5%) and shorter intensive care unit (17.2 ± 1.2 vs. 22.7 ± 6.3 days) and hospital (23.7 ± 2.8 vs. 29.8 ± 11.1 days) stay (p < 0.05). Of the 81 patients assigned to tracheal aspirate, the 17 (21%) who achieved de-escalation of therapy had reduced 15-day mortality (5.8% vs. 34.3%), reduced 28-day mortality (11.6% vs. 45.3%), and shorter intensive care unit (17.2 ± 1.6 vs. 22.4 ± 6.4 days) and hospital (23.1 ± 4.4 vs. 29.9 ± 11.1 days) stay (p < 0.05). Of the 62 patients assigned to BAL, the 41 (66.1%) who achieved de-escalation of therapy had decreased 15-day mortality (4.8% vs. 23.8%), decreased 28-day mortality (12.1% vs. 38%), and shorter intensive care unit (17.2 ± 1.1 vs. 23.2 ± 6 days) and hospital (23.8 ± 2.4 vs. 29.8 ± 11.4 days) stay (p < 0.05). Conclusions For patients with VAP who have had appropriate treatment and shown a favorable clinical response, mortality and duration of stay can be further improved by de-escalation therapy.     

Intravenous tezosentan improves gas exchange and hemodynamics in acute lung injury secondary to meconium aspiration

Objective Meconium aspiration induces acute lung injury (ALI) and subsequent pulmonary arterial hypertension (PAH) which may lead to right ventricular failure. Increase of endothelin-1, thromboxane-A, and phosphodiesterases are discussed molecular mechanisms. We investigated the intrapulmonary and hemodynamic effects of the intravenous dual endothelin A and B receptor blocker tezosentan and inhalational iloprost in a model of ALI due to meconium aspiration. Design Animal study. Setting University-affiliated research laboratory. Subjects White farm pigs. Interventions Acute lung injury was induced in 24 pigs by instillation of meconium. Animals were randomly assigned to four groups to receive either intravenous tezosentan, inhalational iloprost, or combined tezosentan and iloprost, or to serve as controls. Measurements and results After meconium aspiration-induced lung injury each treatment increased oxyhemoglobin saturations (TEZO: 88 ± 6% (p = 0.02), ILO: 85 ± 13% (p = 0.05), TEZO-ILO: 89 ± 6% (p = 0.02), control: 70 ± 18%). TEZO but not ILO significantly decreased pulmonary arterial pressure and pulmonary vascular resistance (both p < 0.01). ILO alone decreased intrapulmonary shunt blood flow (p < 0.01). Compared with control, TEZO-ILO yielded the highest arterial partial pressure of oxygen (70 ± 6 torr vs.49 ± 9 torr, p = 0.04), although it decreased arterial blood pressure (change from 71 ± 13 mmHg to 62 ± 12 mmHg vs.85 ± 14 mmHg to 80  ± 11 mmHg (p = 0.01). Conclusions Intravenous TEZO improves pulmonary gas exchange and hemodynamics in experimental acute lung injury secondary to meconium aspiration. Inhaled ILO improves gas exchange only, thereby reducing intrapulmonary shunt blood flow. Combination of TEZO and ILO marginally improves pulmonary gas exchange at the disadvantage of pulmonary selectivity. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Insulin glargine supplementation during early management phase of diabetic ketoacidosis in children

Objective To study the effect of subcutaneous administration of insulin glargine on the rate of resolution of acidosis and intravenous insulin infusion requirement in children with moderate and severe diabetic ketoacidosis (DKA). Study design Retrospective cohort study. Setting Pediatric intensive care unit of a university-based children's hospital. Patients Children with moderate to severe DKA admitted between March 2001 and February 2003. Results The outcomes of children who received 0.3 units/kg of subcutaneous insulin glargine in the first 6 h of management in addition to the standard treatment (n = 12) were compared with those of children who received standard treatment alone (n = 59). Measured outcomes included dose of intravenous insulin required, duration of insulin infusion and acidosis correction time. The two groups were similar in demographics and severity of illness. The mean time for acidosis correction (venous pH ≥ 7.3) in the insulin glargine group was shorter than the standard therapy group (12.4 ± 2.9 h and 17.1 ± 6.2 h respectively, p < 0.001). The insulin infusion time was shorter in the insulin glargine group (14.8 ± 6.0 h vs 24.4 ± 9.0 h, p < 0.001). There was a trend towards shorter total hospital stay in the glargine group (3.2 ± 1.0 days vs 3.72 ± 1.06 days). Conclusions In our small series of children with moderate and severe DKA, supplementing with subcutaneous insulin glargine led to a faster resolution of acidosis without any adverse effects. This could potentially lead to a shorter need for insulin infusion and a shorter ICU length of stay.     

Renal blood flow and function during recovery from experimental septic acute kidney injury

Objective To measure renal blood flow (RBF) and renal function during recovery from experimental septic acute kidney injury (AKI). Design Controlled experimental study. Subjects Nine merino ewes. Setting University physiology laboratory. Intervention We recorded systemic and renal hemodynamics during a 96-h observation period (control) via implanted transit-time flow probes. We then compared this period with 96 h of septic AKI (48 h of Escherichia coli infusion) and subsequent recovery (48 h of observation after stopping E. coli). Measurements and results Compared with the control period, E. coli infusion induced hyperdynamic sepsis (increased cardiac output and decreased blood pressure) and septic AKI (serum creatinine 65.4 ± 8.7 vs. 139.9 ± 33.0 μmol/l; creatinine clearance 73.8 ± 12.2 vs. 40.2 ± 17.2 ml/min; p < 0.05) with a mortality of 22%. RBF increased (278.8 ± 33.9 vs. 547.9 ± 124.8 ml/min; p < 0.05) as did renal vascular conductance (RVC). During recovery, we observed a decrease in RVC and RBF with all values returning to control levels. Indices of tubular function [fractional excretion of sodium (FENa) and urea (FEUn) and urinary sodium concentration (UNa)], which had been affected by sepsis, returned to control values after 18 h of recovery, as did serum creatinine. Conclusions Infusion of E. coli induced a hyperdynamic circulatory state with hyperemic AKI. Recovery was associated with relative renal vasoconstriction and reduction in RBF and RVC back to control levels. Indices of tubular function normalized more rapidly than changes in RBF. This article is discussed in the editorial available at: .     

Respiratory load compensation during mechanical ventilation—proportional assist ventilation with load-adjustable gain factors versus pressure support

Rationale In mechanically ventilated patients respiratory system impedance may vary from time to time, resulting, with pressure modalities of ventilator support, in changes in the level of assistance. Recently, implementation of a closed-loop adjustment to continuously adapt the level of assistance to changes in respiratory mechanics has been designed to operate with proportional assist ventilation (PAV+).Objectives The aim of this study was to assess, in critically ill patients, the short-term steady-state response of respiratory motor output to added mechanical respiratory load during PAV+ and during pressure support (PS).Patients and interventions In 10 patients respiratory workload was increased and the pattern of respiratory load compensation was examined during both modes of support.Measurements and results Airway and transdiaphragmatic pressures, volume and flow were measured breath by breath. Without load, both modes provided an equal support as indicated by a similar pressure–time product of the diaphragm per breath, per minute and per litre of ventilation. With load, these values were significantly lower (p < 0.05) with PAV+ than those with PS (5.1 ± 3.7 vs 6.1 ± 3.4 cmH₂O.s, 120.9 ± 77.6 vs 165.6 ± 77.5 cmH₂O.s/min, and 18.7 ± 15.1 vs 24.4 ± 16.4 cmH₂O.s/l, respectively). Contrary to PS, with PAV+ the ratio of tidal volume (V_T) to pressure–time product of the diaphragm per breath (an index of neuroventilatory coupling) remained relatively independent of load. With PAV+ the magnitude of load-induced V_T reduction and breathing frequency increase was significantly smaller than that during PS.Conclusion In critically ill patients the short-term respiratory load compensation is more efficient during proportional assist ventilation with adjustable gain factors than during pressure support.Electronic supplementary material The electronic reference of this article is . The online full-text version of this article includes electronic supplementary material. This material is available to authorised users and can be accessed by means of the ESM button beneath the abstract or in the structured full-text article. To cite or link to this article you can use the above reference.     

Can dynamic indicators help the prediction of fluid responsiveness in spontaneously breathing critically ill patients?

Objective To investigate whether the respiratory changes in arterial pulse (ΔPP) and in systolic pressure (ΔSP) could predict fluid responsiveness in spontaneously breathing (SB) patients. Because changes in intrathoracic pressure during spontaneous breathing (SB) might be insufficient to modify loading conditions of the ventricles, performances of indicators were also assessed during a forced respiratory maneuver. Design Prospective interventional study. Setting A 34-bed university hospital medico-surgical ICU. Patients and participants Thirty-two SB patients with clinical signs of hemodynamic instability. Intervention A 500-ml volume expansion (VE). Measurements and results Cardiac index, assessed using transthoracic echocardiography, increased by at least 15% after VE in 19 patients (responders). At baseline, only dynamic indicators were higher in responders than in nonresponders (13 ± 5% vs. 7 ± 3%, p = 0.003 for ΔPP and 10 ± 4% vs. 6 ± 2%, p = 0.002 for ΔSP). Moreover, they significantly decreased after VE (11 ± 5% to 6 ± 4%, p < 0.001 for ΔPP and 8 ± 4% to 6 ± 3%, p < 0.001 for ΔSP). ΔPP and ΔSP areas under the ROC curve were high (0.81 ± 0.08 and 0.82 ± 0.08; p = 0.888, respectively). A ΔPP ≥ 12% predicted fluid responsiveness with high specificity (92%) but poor sensitivity (63%). The forced respiratory maneuver reproducing a dyspneic state decreased the predictive power. Conclusions Due to their lack of sensitivity and their dependence to respiratory status, ΔPP and ΔSP are clearly less reliable to predict fluid responsiveness during SB than in mechanically ventilated patients. However, when their baseline value is high without acute right ventricular dysfunction in a participating patient, a positive response to fluid is likely. This study was presented at the American Thoracic Society international conference, 2005, San Diego, California. This article is discussed in the editorial available 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 intra-abdominal pressure affects respiratory variations in arterial pressure in normovolaemic and hypovolaemic mechanically ventilated healthy pigs

Objective To evaluate the effect of increased intra-abdominal pressure (IAP) on the systolic and pulse pressure variations induced by positive pressure ventilation in a porcine model. Design and setting Experimental study in a research laboratory. Subjects Seven mechanically ventilated and instrumented pigs prone to normovolaemia and hypovolaemia by blood withdrawal. Intervention Abdominal banding gradually increased IAP in 5-mmHg steps up to 30 mmHg. Measurements and main results Variations in systolic pressure, pulse pressure, inferior vena cava flow, and pleural and transmural (LVEDPtm) left-ventricular end-diastolic pressure were recorded at each step. Systolic pressure variations were 6.1 ± 3.1%, 8.5 ± 3.6% and 16.0 ± 5.0% at 0, 10, and 30 mmHg IAP in normovolaemic animals (mean ± SD; p< 0.01 for IAP effect). They were 12.7 ± 4.6%, 13.4 ± 6.7%, and 23.4 ± 6.3% in hypovolaemic animals (p< 0.01 vs normovolaemic group) for the same IAP. Fluctuations of the inferior vena cava flow disappeared as the IAP increased. Breath cycle did not induce any variations of LVEDPtm for 0 and 30 mmHg IAP. Conclusions In this model, the systolic pressure and pulse pressure variations, and inferior vena cava flow fluctuations were dependent on IAP values which caused changes in pleural pressure swing, and this dependency was more marked during hypovolaemia. The present study suggests that dynamic indices are not exclusively related to volaemia in the presence of increased IAP. However, their fluid responsiveness predictive value could not be ascertained as no fluid challenge was performed. This article is discussed in the editorial available at:     

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: .     

Transcranial Doppler ultrasound goal-directed therapy for the early management of severe traumatic brain injury

Objective To evaluate the usefulness of early transcranial Doppler ultrasound (TCD) goal-directed therapy after severe traumatic brain injury initiated before invasive cerebral monitoring is available. Design Prospective, observational clinical study. Setting Surgical intensive care unit, university hospital. Patients and participants Twenty-four severely brain-injured patients. Interventions All patients had TCD measurements immediately on admission (T0) and when invasive cerebral monitoring was available (T1). TCD was considered abnormal when two out of three measured values were outside the following limits: Vm < 30 cm/s, Vd < 20 cm/s, PI  > 1.4. When admission TCD was abnormal, attending physicians modified treatment to increase cerebral perfusion pressure. Measurements and results Admission TCD was performed 18 ± 11 min (T0) after admission, whereas cerebral inasive monitoring was available 242 ± 116 min (T1) after admission. At T0, 11 (46%) patients had abnormal TCD values (group 1) and 13 had normal TCD values (group 2); mean arterial pressure was comparable between groups. All group 1 patients received mannitol and/or norepinephrine. At T1, mean arterial pressure was increased compared to admission in group 1 (105 ± 17 mmHg vs. 89 ± 15 mmHg, p < 0.05) and only two patients had still an abnormal TCD. Although group 1 patients had higher intracranial pressure than those of group 2 (32 ± 13 mmHg vs. 22 ± 10 mmHg, p < 0.01), both cerebral perfusion pressure and jugular venous oxygen saturation were comparable between the groups. Conclusions The use of TCD at hospital admission allows identification of severely brain-injured patients with brain hypoperfusion. In such high-risk patients, early TCD goal-directed therapy can restore normal cerebral perfusion and might then potentially help in reducing the extent of secondary brain injury.     

Monitoring brain tissue oxygen tension in brain-injured patients reveals hypoxic episodes in normal-appearing and in peri-focal tissue

Objective We compared brain tissue oxygen tension (PtiO₂) measured in peri-focal and in normal-appearing brain parenchyma on computerized tomography (CT) in patients following traumatic brain injury (TBI). Design Prospective observational study. Setting Neurointensive care unit. Patients and participants Thirty-two consecutive TBI patients were subjected to PtiO₂ monitoring. Interventions Peri-focal tissue was identified by the presence of a hypodense area of the contusion and/or within 1 cm from the core of the contusion. The position of the tip of the PtiO₂ probe was assessed at follow-up CT scan. Measurements and results Mean PtiO₂ in the peri-contusional tissue was 19.7 ± 2.1 mmHg and was lower than PtiO₂ in normal-appearing tissue (25.5 ± 1.5 mmHg, p < 0.05), despite a greater cerebral perfusion pressure (CPP) (73.7 ± 2.3 mmHg vs. 67.4 ± 1.4 mmHg, p < 0.05). We observed both in peri-focal tissue and in normal-appearing tissue episodes of brain hypoxia (PtiO₂ < 20 mmHg for at least 10 min), whose median duration was longer in peri-focal tissue than in normal-appearing tissue (51% vs. 34% of monitoring time, p < 0.01). In peri-focal tissue, we observed a progressive PtiO₂ increase from pathologic to normal values (p < 0.01). Conclusions Multiple episodes of brain hypoxia occurred over the first 5 days following severe TBI. PtiO₂ was lower in peri-contusional tissue than in normal-appearing tissue. In peri-contusional tissue, a progressive increase of PtiO₂ from pathologic to normal values was observed over time, suggestive of an improvement at microcirculatory level.     

Goal-directed fluid management reduces vasopressor and catecholamine use in cardiac surgery patients

Objective We examined whether guiding therapy by an algorithm based on optimizing the global end-diastolic volume index (GEDVI) reduces the need for vasopressor and inotropic support and helps to shorten ICU stay in cardiac surgery patients. Design and setting Single-center clinical study with a historical control group at an university hospital. Patients Forty cardiac bypass surgery patients were included prospectively and compared with a control group. Interventions In the goal-directed therapy (GDT) group hemodynamic management was guided by an algorithm based on GEDVI. Hemodynamic goals were: GEDVI above 640 ml/m², cardiac index above 2.5 l/min/m², and mean arterial pressure above 70 mmHg. The control group was treated at the discretion of the attending physician based on central venous pressure, mean arterial pressure, and clinical evaluation. Results In the GDT group duration of catecholamine and vasopressor dependence was shorter (187 ± 70 vs. 1458 ± 197 min), and fewer vasopressors (0.73 ± 0.32 vs. 6.67 ± 1.21 mg) and catecholamines (0.01 ± 0.01 vs. 0.83 ± 0.27 mg) were administered. They received more colloids (6918 ± 242 vs. 5514 ± 171 ml). Duration of mechanical ventilation (12.6 ± 3.6 vs. 15.4 ± 4.3 h) and time until achieving status of fit for ICU discharge (25 ± 13 vs. 33 ± 17 h) was shorter in the GDT group. Conclusions Guiding therapy by an algorithm based on GEDVI leads to a shortened and reduced need for vasopressors, catecholamines, mechanical ventilation, and ICU therapy in patients undergoing cardiac surgery. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

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.     

Ultrasound evaluation of central veinsin the intensive care unit:effects of dynamic manoeuvres

Objective To determine: (1) the proportion of small (< 5 mm) or thrombosed internal jugular veins (IJV) and femoral veins (FV) in which catheter placement would be difficult without ultrasound guidance; (2) which position increases central vein sizes and may facilitate cannulation of these vessels. Design Prospective study. Setting Twelve-bed adult medical intensive care unit. Patients and participants Sixty patients (62 ±  19 years, SAPS II score 36 ± 17). Interventions Ultrasound examinations of the IJV and FV in supine, Trendelenburg (T) and reverse Trendelenburg (Ti) positions. Measurements and results Maximum diameter and cross-sectional area (CSA) were measured. Venous catheter placement would have been difficult (diameter < 5 mm) or even impossible (thrombosis) for 22% of right IJV, 13% of left IJV, 2% of left and 2% of right FV. In the T position, the CSA of the IJV increased (right IJV: 1.7 ±  1.4 to 2.01 ±  1.34 cm², left IJV: 1.18 ±  0.81 to 1.34 ±  0.85 cm²; p < 0.05) and theCSA of the FV decreased (right FV: 1.42 ±  0.61 to 1.22 ±  0.58 cm², left FV: 1.51 ±  0.62 to 1.26 ±  0.58 cm²; p < 0.05). In the Ti position, the CSA of the IJV decreased (right IJV: 1.7 ±  1.4 to 1.35 ±  1.35 cm², left IJV: 1.18 ±  0.81 to 0.87 ±  0.62 cm²; p < 0.05) and the CSA of the FV increased (right FV: 1.42 ±  0.61 to 1.66 ±  0.65 cm², left FV: 1.51 ±  0.62 to 1.65 ±  0.68 cm²; p < 0.05). In two-thirds of patients, the right IJV was significantly larger than the left IJV. Conclusions Ultrasonography should be performed before at least central venous catheter placement to detect the presence of deep vein thrombosis or vessels less than 5 mm in diameter. Some positions increase veins' diameter at least internally, T position increasing IJV size and Ti position increasing FV size.     

Effect of blood pressure on plasma volume loss in the rat under increased permeability

Objective To evaluate the effects of change in blood pressure on plasma volume under increased permeability. Design Prospective randomized laboratory study. Subject Sixty-one adult male Sprague–Dawley rats. Interventions Permeability was increased via an anaphylactic reaction by injection of 0.5 ml dextran 70. One hour later, volume expansion with 15 ml/kg of 5% albumin was given for 15 min. Plasma volume was measured just before and 2.5 h after the albumin infusion (¹²⁵I-albumin tracer technique). The study included a control group, a noradrenalin group and a metoprolol/clonidine group (n = 10 in each group). The vasoactive treatment started after the albumin infusion and continued throughout the experiment. We also investigated the effect of noradrenalin on plasma volume under hypovolemia. Central venous pressure was measured to estimate the venous pressure effect of noradrenalin (n = 6). The results were compared with corresponding plasma volume effects of noradrenalin under normal permeability. Results The remaining increase in plasma volume 2.5 h after the albumin infusion was 11.8 ± 3.6 ml/kg in the control group, 0.5 ± 6.3 ml/kg in the noradrenalin group (p < 0.01) and 12.6 ± 4.9 ml/kg in the metoprolol/clonidine group (ns). The loss of plasma volume by noradrenalin under hypovolemia was 3.5 ± 3.0 ml/kg. The remaining increase in plasma volume after the albumin and noradrenalin treatment under normal permeability was 13.7 ± 3.4 ml/kg. Conclusion Increase in blood pressure by noradrenalin induces loss of plasma volume, which is much greater under increased than under normal permeability and less pronounced in hypovolemia. According to the two-pore theory of transvascular fluid exchange, the loss may be explained by increased hydrostatic capillary pressure. This article is discussed in the editorial available at: .