Philippe Seguin

Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies

BACKGROUND Estimating attributable mortality of ventilator-associated pneumonia has been hampered by confounding factors, small sample sizes, and the difficulty of doing relevant subgroup analyses. We estimated the attributable mortality using the individual original patient data of published randomised trials of ventilator-associated pneumonia prevention. METHODS We identified relevant studies through systematic review. We analysed individual patient data in a one-stage meta-analytical approach (in which we defined attributable mortality as the ratio between the relative risk reductions [RRR] of mortality and ventilator-associated pneumonia) and in competing risk analyses. Predefined subgroups included surgical, trauma, and medical patients, and patients with different categories of severity of illness scores. FINDINGS Individual patient data were available for 6284 patients from 24 trials. The overall attributable mortality was 13%, with higher mortality rates in surgical patients and patients with mid-range severity scores at admission (ie, acute physiology and chronic health evaluation score [APACHE] 20-29 and simplified acute physiology score [SAPS 2] 35-58). Attributable mortality was close to zero in trauma, medical patients, and patients with low or high severity of illness scores. Competing risk analyses could be done for 5162 patients from 19 studies, and the overall daily hazard for intensive care unit (ICU) mortality after ventilator-associated pneumonia was 1·13 (95% CI 0·98-1·31). The overall daily risk of discharge after ventilator-associated pneumonia was 0·74 (0·68-0·80), leading to an overall cumulative risk for dying in the ICU of 2·20 (1·91-2·54). Highest cumulative risks for dying from ventilator-associated pneumonia were noted for surgical patients (2·97, 95% CI 2·24-3·94) and patients with mid-range severity scores at admission (ie, cumulative risks of 2·49 [1·81-3·44] for patients with APACHE scores of 20-29 and 2·72 [1·95-3·78] for those with SAPS 2 scores of 35-58). INTERPRETATION The overall attributable mortality of ventilator-associated pneumonia is 13%, with higher rates for surgical patients and patients with a mid-range severity score at admission. Attributable mortality is mainly caused by prolonged exposure to the risk of dying due to increased length of ICU stay. FUNDING None.

Clinical review: The liver in sepsis

During sepsis, the liver plays a key role. It is implicated in the host response, participating in the clearance of the infectious agents/products. Sepsis also induces liver damage through hemodynamic alterations or through direct or indirect assault on the hepatocytes or through both. Accordingly, liver dysfunction induced by sepsis is recognized as one of the components that contribute to the severity of the disease. Nevertheless, the incidence of liver dysfunction remains imprecise, probably because current diagnostic tools are lacking, notably those that can detect the early liver insult. In this review, we discuss the epidemiology, diagnostic tools, and impact on outcome as well as the pathophysiological aspects, including the cellular events and clinical picture leading to liver dysfunction. Finally, therapeutic considerations with regard to the weakness of the pertinent specific approach are examined.

Effects of epinephrine compared with the combination of dobutamine and norepinephrine on gastric perfusion in septic shock

In septic shock, the alteration of the gut barrier contributes to the development of multiple organ failure. The aim of the study was to compare epinephrine with the combination of dobutamine and norepinephrine on gastric perfusion in patients with septic shock.

Effects of epinephrine on right ventricular function in patients with severe septic shock and right ventricular failure: a preliminary descriptive study.

Objective: To recognize patients with unresponsive septic shock and right ventricular (RV) failure and to evaluate the effects of epinephrine on RV performance in these patients. Design: Prospective descriptive study. Setting: Medical intensive care unit. Subjects: 14 consecutive patients in septic shock unresponsive to fluid loading, dopamine, and dobutamine. Interventions: Evaluation of RV function by thermodilution with a pulmonary artery catheter equipped with a rapid-response thermistor. Measurements were obtained before and during epinephrine infusion to achieve a systolic arterial pressure ≥ 90 mmHg or a mean arterial pressure (MAP) ≥ 70 mmHg. Results: At the time of inclusion in the study the hemodynamic pattern in the 14 patients was as follows: (MAP) 58 ± 14 mmHg, systemic vascular resistance (SVR) 1046 ± 437 dyne · s · cm–5· m–2, pulmonary artery occlusion pressure (PAOP) 14 ± 4 mmHg, mean pulmonary artery pressure (MPAP) 24 ± 4 mmHg, right arterial pressure (RAP) 11 ± 4 mmHg, cardiac index (CI) 4 ± 1.7 l/min per m2. During epinephrine infusion, MAP, CI and stroke volume index (SVI) were increased (27 %, p < 0.01; 20 %, p < 0.01; 15 %, p < 0.05, respectively). There was no change in PAOP, SVR or heart rate. Seven patients (group A) had marked RV failure defined by both RV dilation [RV end-diastolic volume index (RVEDVI) > 92 ml/m2] and low RV ejection factor (RVEF) (< 52 %) and 7 did not (group B). Group A had a lower baseline RVEF than group B (24 ± 7 vs 45 ± 9 %, p < 0.05), a higher RVEDVI (134 ± 28 vs 79 ± 17 ml/m2, p < 0.01), and a higher RVES (systolic) VI (103 ± 30 vs 43 ± 11 ml/m2, p < 0.01). The other hemodynamics, especially RAP and RV stroke work index (RVSWI) were no different in the two groups and did not predict RV dysfunction. In group A, epinephrine infusion improved RVEF (25 %, p < 0.05) by a reduction in RVESVI (− 8 %, p < 0.05) without any change in RVEDVI or in RAP, in spite of a rise in MPAP (11 %, p < 0.05). A rise in RVSWI (76 %, p < 0.05), SVI (23 %, p < 0.05), and CI (24 %, p < 0.05) was also achieved. An upward vertical shift of the Frank-Starling relationship RVSWI/RVEDVI and an upward shift to the left of the pressure volume relationship pulmonary artery peak pressure/RVESVI was observed only in the group with RV failure following treatment with epinephrine. In group B (without RV failure), RV parameters were not modified by epinephrine. Conclusion: In patients with severe septic shock, RV dysfunction was identified by the use of an RVEF pulmonary artery catheter and was improved by epinephrine by means of an improvement in RV contractility.

Reproducibility of thermodilution cardiac output determination in critically ill patients : Comparison between bolus and continuous method

Objective. A semi-continuous thermodilution method (CCO) was recently developed to measure cardiac output with less risk of bacterial contamination, fluid overload, and user-induced errors than the classical bolus technique (BCO). Previous comparison between these two methods showed negligible bias. However, large limits of agreement suggest that the two methods are not interchangeable. We hypothesized that this poor agreement may be due to differences in reproducibility.Methods. In 23 critically ill patients, 369 paired measurements of CCO and BCO were compared (range of cardiac outputs: 2.8 to 16 L/min). The reproducibility of BCO and CCO methods was evaluated on a sample of 205 and 209 determinations, respectively.Results. The comparison between the CCO and the BCO methods confirmed previous results: i.e., small bias (−0.39 L/min) and large limits of agreement ⊂-2.06 to +1.28 L/min). Reproducibility showed no bias for either the CCO or the BCO method. Limits of reproducibility agreement between repeated determinations were approximately 50% less for CCO than for BCO method: respectively −0.87 to +0.82 L/min for the CCO method and −1.56 to +1.37 L/min for the BCO method. Consequently, the threshold necessary to ascertain that the difference between two measurements was not due to the internal variability of the method (3 x SEM) was 0.39 for the CCO method and 0.75 L/min for the BCO method.Conclusion. Differences in reproducibility may explain the poor agreement between the CCO and BCO methods. The better reproducibility of the CCO method allows the detection of smaller variations in cardiac output and suggests the superiority of this new method.

Incidence and prognosis of ventilator-associated tracheobronchitis (TAVeM): a multicentre, prospective, observational study

BACKGROUND Ventilator-associated tracheobronchitis has been suggested as an intermediate process between tracheobronchial colonisation and ventilator-associated pneumonia in patients receiving mechanical ventilation. We aimed to establish the incidence and effect of ventilator-associated tracheobronchitis in a large, international patient cohort. METHODS We did a multicentre, prospective, observational study in 114 intensive care units (ICU) in Spain, France, Portugal, Brazil, Argentina, Ecuador, Bolivia, and Colombia over a preplanned time of 10 months. All patients older than 18 years admitted to an ICU who received invasive mechanical ventilation for more than 48 h were eligible. We prospectively obtained data for incidence of ventilator-associated lower respiratory tract infections, defined as ventilator-associated tracheobronchitis or ventilator-associated pneumonia. We grouped patients according to the presence or absence of such infections, and obtained data for the effect of appropriate antibiotics on progression of tracheobronchitis to pneumonia. Patients were followed up until death or discharge from hospital. To account for centre effects with a binary outcome, we fitted a generalised estimating equation model with a logit link, exchangeable correlation structure, and non-robust standard errors. This trial is registered with ClinicalTrials.gov, number NCT01791530. FINDINGS Between Sept 1, 2013, and July 31, 2014, we obtained data for 2960 eligible patients, of whom 689 (23%) developed ventilator-associated lower respiratory tract infections. The incidence of ventilator-associated tracheobronchitis and that of ventilator-associated pneumonia at baseline were similar (320 [11%; 10·2 of 1000 mechanically ventilated days] vs 369 [12%; 8·8 of 1000 mechanically ventilated days], p=0·48). Of the 320 patients with tracheobronchitis, 250 received appropriate antibiotic treatment and 70 received inappropriate antibiotics. 39 patients with tracheobronchitis progressed to pneumonia; however, the use of appropriate antibiotic therapy for tracheobronchitis was associated with significantly lower progression to pneumonia than was inappropriate treatment (19 [8%] of 250 vs 20 [29%] of 70, p<0·0001; crude odds ratio 0·21 [95% CI 0·11-0·41]). Significantly more patients with ventilator-associated pneumonia died (146 [40%] of 369) than those with tracheobronchitis (93 [29%] of 320) or absence of ventilator-associated lower respiratory tract infections (673 [30%] of 2271, p<0·0001). Median time to discharge from the ICU for survivors was significantly longer in the tracheobronchitis (21 days [IQR 15-34]) and pneumonia (22 [13-36]) groups than in the group with no ventilator-associated lower respiratory tract infections (12 [8-20]; hazard ratio 1·65 [95% CI 1·38-1·97], p<0·0001). INTERPRETATION This large database study emphasises that ventilator-associated tracheobronchitis is a major health problem worldwide, associated with high resources consumption in all countries. Our findings also show improved outcomes with use of appropriate antibiotic treatment for both ventilator-associated tracheobronchitis and ventilator-associated pneumonia, underlining the importance of treating both infections, since inappropriate treatment of tracheobronchitis was associated with a higher risk of progression to pneumonia. FUNDING None.

Clinical review: Fever in septic ICU patients - friend or foe?

In recent years, fever control in critically ill patients by medications and/or external cooling has gained widespread use, notably in patients suffering from neurological injuries. Nevertheless, such a strategy in septic patients is not supported by relevant data. Indeed, in response to sepsis, experimental and clinical studies argue that fever plays a key role in increasing the clearance of microorganisms, the immune response and the heat shock response. Moreover, fever is a cornerstone diagnostic sign in clinical practice, which aids in early and appropriate therapy, and allows physicians to follow the infection course. After discussing the physiological aspects of fever production, the present review aims to delineate the advantages and drawbacks of fever in septic patients. Finally, the treatment of fever by pharmacological and/or physical means is discussed with regards to their drawbacks, which argues for their careful use in septic patients in the absence of clinical relevance.

Estimation of the diameter and cross-sectional area of the internal jugular veins in adult patients

IntroductionUnawareness of an asymmetry between the right and left internal jugular vein (IJV) and methodological pitfalls in previous studies raise concerns about such asymmetry. Hence the aim of this prospective non-interventional study was to validate the hypothesis that right IJV diameter is greater than those of left IJV and to determine the cross-sectional area of the IJVs using computed tomography (CT)-scans and original automatic software.MethodsAll consecutive adult outpatients who underwent a thoracic contrast-enhanced (TCE) helical CT-scan during a 5-month period were included. To determine diameter and cross sectional area of the IJVs, we used Advanced Vessel Analysis software integrated in a CT-scan (Advanced Vessel Analysis on Advantage Workstation Windows 4.2; General Electrics) allowing automatic segmentation of vessels and calculation of their diameters and cross-sectional areas.ResultsA total of 360 TCE CT-scans was performed; 170 were excluded from the analysis. On the remaining 190 CT scans, the diameter and cross-sectional area of the right IJV were significantly greater than those of the left IJV (17 ± 5 mm [median: 17 mm, range: 13 to 20 mm] vs. 14 ± 5 mm [median: 13 mm, range: 10 to 16 mm], P < 0.001; and 181 ± 111 mm2 [median: 160 mm2, range: 108 to 235 mm2] vs. 120 ± 81 mm2 [median: 102 mm2, range: 63 to 168 mm2], P < 0.001, respectively).ConclusionsIn a general population of adult outpatients, the diameter and cross-sectional area of the right IJV were significantly greater than those of the left IJV. This could be an additional argument to prefer right over left IJV cannulation.

Dopexamine and norepinephrine versus epinephrine on gastric perfusion in patients with septic shock: a randomized study [NCT00134212]

IntroductionMicrocirculatory blood flow, and notably gut perfusion, is important in the development of multiple organ failure in septic shock. We compared the effects of dopexamine and norepinephrine (noradrenaline) with those of epinephrine (adrenaline) on gastric mucosal blood flow (GMBF) in patients with septic shock. The effects of these drugs on oxidative stress were also assessed.MethodsThis was a prospective randomized study performed in a surgical intensive care unit among adults fulfilling usual criteria for septic shock. Systemic and pulmonary hemodynamics, GMBF (laser-Doppler) and malondialdehyde were assessed just before catecholamine infusion (T0), as soon as mean arterial pressure (MAP) reached 70 to 80 mmHg (T1), and 2 hours (T2) and 6 hours (T3) after T1. Drugs were titrated from 0.2 μg kg-1 min-1 with 0.2 μg kg-1 min-1 increments every 3 minutes for epinephrine and norepinephrine, and from 0.5 μg kg-1 min-1 with 0.5 μg kg-1 min-1 increments every 3 minutes for dopexamine.ResultsTwenty-two patients were included (10 receiving epinephrine, 12 receiving dopexamine–norepinephrine). There was no significant difference between groups on MAP at T0, T1, T2, and T3. Heart rate and cardiac output increased significantly more with epinephrine than with dopexamine–norepinephrine, whereas. GMBF increased significantly more with dopexamine–norepinephrine than with epinephrine between T1 and T3 (median values 106, 137, 133, and 165 versus 76, 91, 90, and 125 units of relative flux at T0, T1, T2 and T3, respectively). Malondialdehyde similarly increased in both groups between T1 and T3.ConclusionIn septic shock, at doses that induced the same effect on MAP, dopexamine–norepinephrine enhanced GMBF more than epinephrine did. No difference was observed on oxidative stress.

Effect of an anesthesia with propofol compared with desflurane on free radical production and liver function after partial hepatectomy.

Propofol has shown antioxidant properties, but no study has focused on liver resection surgery. The aim of this study was to investigate the effect of an anesthesia with propofol compared with desflurane on oxidative stress and hepatic function during and after partial hepatectomy. This was a prospective randomized study performed on two parallel groups. The primary endpoint was malondialdehyde (MDA) plasma concentration 30 min after hepatic vascular unclamping. Hepatic damages were evaluated by plasma levels of alpha‐glutathione S‐transferase (α‐GST) 120 min after hepatic vascular unclamping and of aminotransferases at 120 min and on days 1, 2, 5, and 10. Liver function recovery was assessed by monoethylglycinexylidide (MEGX) formation 15 min after lidocaine injection on day 2 and by prothrombin time and plasma factor V at 120 min and on days 1, 2, 5, and 10. Thirty patients were analyzed (propofol group: 17; desflurane group: 13). There was no significant difference between groups for MDA plasma concentration 30 min after hepatic vascular unclamping (mean ± standard‐deviation: 1.28 ± 0.40 and 1.21 ± 0.29 in propofol and desflurane groups, respectively, P = 0.608). Plasma levels of α‐GST at 120 min were lower in propofol than in desflurane group (142.2 ± 75.4 vs. 205.7 ± 66.5, P = 0.023), and MEGX on day 2 was higher (0.092 ± 0.096 vs. 0.036 ± 0.020, P = 0.007). No differences between groups were observed with regard to plasma levels of aminotransferases, prothrombin time, and plasma factor V. Our study showed that in patients undergoing partial hepatectomy, propofol did not reduce MDA formation but seemed to display a protective effect on hepatic damages and liver function when compared to desflurane.