J.-Y. Lefrant

Training is required to improve the reliability of esophageal Doppler to measure cardiac output in critically ill patients

Objectives: Assessment of and effect of training on reliability of esophageal Doppler (ED) versus thermodilution (TD) for cardiac output (CO) measurement.Design: Prospective study.Setting: Intensive care unit of a university hospital.Patients: 64 consecutive critically ill patients requiring a pulmonary artery catheter, sedation, and mechanical ventilation.Interventions: Esophageal Doppler CO measurements were performed by the same operator, whereas TD CO measurements were carried out by other independent operators. A training period involving the first 12 patients made the operator self-confident. In the remaining patients, the reliability of ED was assessed (evaluation period), using correlation coefficients and the Bland and Altman diagram. Between training and evaluation periods, correlation coefficients, biases, and limits of agreement were compared.Measurements and results: During training and evaluation periods, 107 and 320 CO measurements were performed in 11 out of 12 patients and in 49 out of 52 patients, respectively. Continuous CO monitoring was achieved in 6 out of 11 patients and in 38 out of 49 patients during training and evaluation periods, respectively. Between the two periods, correlation coefficients increased from 0.53 to 0.89 (p < 0.001), bias decreased from 1.2 to 0.1 l.min−1 (p < 0.001), and limits of agreement decreased from 3.2 to 2.2 l.min−1 (p < 0.001).Conclusion: A period of training involving no more than 12 patients is probably required to ensure reliability of CO measurement by ED.

Respiratory variations of inferior vena cava diameter to predict fluid responsiveness in spontaneously breathing patients with acute circulatory failure: need for a cautious use

IntroductionTo investigate whether respiratory variation of inferior vena cava diameter (cIVC) predict fluid responsiveness in spontaneously breathing patients with acute circulatory failure (ACF).MethodsForty patients with ACF and spontaneous breathing were included. Response to fluid challenge was defined as a 15% increase of subaortic velocity time index (VTI) measured by transthoracic echocardiography. Inferior vena cava diameters were recorded by a subcostal view using M Mode. The cIVC was calculated as follows: (Dmax - Dmin/Dmax) × 100 and then receiver operating characteristic (ROC) curves were generated for cIVC, baseline VTI, E wave velocity, E/A and E/Ea ratios.ResultsAmong 40 included patients, 20 (50%) were responders (R). The causes of ACF were sepsis (n = 24), haemorrhage (n = 11), and dehydration (n = 5). The area under the ROC curve for cIVC was 0.77 (95% CI: 0.60-0.88). The best cutoff value was 40% (Se = 70%, Sp = 80%). The AUC of the ROC curves for baseline E wave velocity, VTI, E/A ratio, E/Ea ratio were 0.83 (95% CI: 0.68-0.93), 0.78 (95% CI: 0.61-0.88), 0.76 (95% CI: 0.59-0.89), 0.58 (95% CI: 0.41-0.75), respectively. The differences between AUC the ROC curves for cIVC and baseline E wave velocity, baseline VTI, baseline E/A ratio, and baseline E/Ea ratio were not statistically different (p = 0.46, p = 0.99, p = 1.00, p = 0.26, respectively).ConclusionIn spontaneously breathing patients with ACF, high cIVC values (>40%) are usually associated with fluid responsiveness while low values (< 40%) do not exclude fluid responsiveness.

A comparison of the pharmacodynamics and pharmacokinetics of bupivacaine, ropivacaine (with epinephrine) and their equal volume mixtures with lidocaine used for femoral and sciatic nerve blocks: a double-blind randomized study.

BACKGROUND: Mixtures of lidocaine with a long-acting local anesthetic are commonly used for peripheral nerve block. Few data are available regarding the safety, efficacy, or pharmacokinetics of mixtures of local anesthetics. In the current study, we compared the effects of bupivacaine 0.5% or ropivacaine 0.75% alone or in a mixed solution of equal volumes of bupivacaine 0.5% and lidocaine 2% or ropivacaine 0.75% and lidocaine 2% for surgery after femoral-sciatic peripheral nerve block. The primary end point was onset time. METHODS: In a double-blind, randomized study, 82 adults scheduled for lower limb surgery received a sciatic (20 mL) and femoral (20 mL) peripheral nerve block with 0.5% bupivacaine (200 mg), a mixture of 0.5% bupivacaine 20 mL (100 mg) with 2% lidocaine (400 mg), 0.75% ropivacaine (300 mg) or a mixture of 0.75% ropivacaine 20 mL (150 mg) with 2% lidocaine (400 mg). Each solution contained epinephrine 1:200,000. Times to perform blocks, onset times (end of injection to complete sensory and motor block), duration of sensory and motor block, and morphine consumption via IV patient-controlled analgesia were compared. Venous blood samples of 5 mL were collected for determination of drug concentration at 0, 5, 15, 30, 45, 60, and 90 min after placement of the block. RESULTS: Patient demographics and surgical times were similar for all four groups. Sciatic onset times (sensory and motor block) were reduced by combining lidocaine with the long-acting local anesthetic. The onset of bupivacaine-lidocaine was 16 ± 9 min versus 28 ± 12 min for bupivacaine alone. The onset of ropivacaine-lidocaine was 16 ± 12 min versus 23 ± 12 for ropivacaine alone. Sensory blocks were complete for all patients within 40 min for those receiving bupivacaine–lidocaine versus 60 min for those receiving bupivacaine alone and 30 min for those receiving ropivacaine–lidocaine versus 40 min for those receiving ropivacaine alone (P < 0.05). Duration of sensory and motor block was significantly shorter in mixture groups. There was no difference among groups for visual analog scale pain scores and morphine consumption during the 48 h postoperative period, except for bupivacaine alone (median: 9 mg) versus bupivacaine–lidocaine mixture (15 mg), P < 0.01. There was no difference in the incidence of adverse events among groups. Plasma concentrations of bupivacaine and ropivacaine were higher, and remained elevated longer, in patients who received only the long-acting local anesthetic compared to patients who received the mixture of long-acting local anesthetic with lidocaine (P < 0.01). CONCLUSION: Mixtures of long-acting local anesthetics with lidocaine induced faster onset blocks of decreased duration. Whether there is a safety benefit is unclear, as the benefit of a decreased concentration of long-acting local anesthetic may be offset by the presence of a significant plasma concentration of lidocaine.

Analgesic efficacy and haemodynamic effects of nefopam in critically ill patients

BACKGROUND Pain management is challenging in intensive care unit (ICU) patients. The analgesic efficacy, tolerance, and haemodynamic effects of nefopam have never been described in critically ill patients. METHODS In consecutive medical-surgical ICU patients who received 20 mg of nefopam i.v. over 30 min, we measured pain, Richmond Agitation Sedation Scale (RASS), respiratory parameters, and adverse drug events at T0 (baseline), T30 (end-of-infusion), T60, and T90 min. Haemodynamic variables were assessed every 15 min from T0 to T60 and T90. Pain was evaluated by the behavioural pain scale (BPS, 3-12) or by the self-reported visual numeric rating scale (NRS, 0-10) according to communication capacity. RESULTS Data were analysed for 59 patients. As early as T30, median NRS and BPS decreased significantly from T0 to a minimum level at T60 for NRS [5 (4-7) vs 1 (1-3), P<0.001] and T90 for BPS [5 (5-6) vs 3 (3-4), P<0.001]. No significant changes were detected for RASS, ventilatory frequency, or oxygen saturation. Increased heart rate and decreased mean arterial pressure, defined as a change ≥15% from baseline, were found in 29% and 27% of patients, respectively. For the 18 patients monitored, cardiac output increased by 19 (7-29)% and systemic vascular resistance decreased by 20 (8-28)%, both maximally at T30. Heat sensation, nausea/vomiting, sweating, and mouth dryness were found, respectively, in 6%, 9%, 22%, and 38% of patients. CONCLUSIONS A single slow infusion of nefopam is effective in critically ill patients who have moderate pain. The risk of tachycardia and increased cardiac output and also hypotension and decreased systemic vascular resistance should be known to evaluate the benefit/risk ratio of its prescription.

Simple coagulation tests improve survival prediction in patients with septic shock

Summary.  Background: Classic mortality prediction models in intensive care units (ICUs) are based on clinical scores, which do not contain any coagulation test (SAPS‐II or SOFA scores). Objectives: To determine whether coagulation tests can improve mortality prediction in patients with septic shock. Patients and methods: One hundred fifty‐eight consecutive patients with septic shock entering our institution’s ICU were investigated on the first day of admission, and deaths were registered during the first month. Results: Among all the coagulation tests performed, only the fibrinogen (Fg) plasma level, together with the SAPS‐II score and the age, were included in our simplified mortality score [area under the receiver operating curve (AUC) 0.927, standard deviation (SD) 0.030], which was more efficient than SAPS‐II and SOFA scores themselves in predicting first‐week mortality, its optimized cut‐off having a very high negative predictive value (NPV) [0.989; 95% confidence interval (CI) 0.967–1.000)]. A simplified score predicting first‐month mortality, containing the prothrombin ratio and the antithrombin activity values in addition to the age, the hemoglobin concentration, and the SAPS‐II and SOFA scores (AUC 0.889, SD 0.026), was found to be superior to the SAPS‐II and SOFA scores, the optimized cut‐off value having a high NPV (0.952; 95% CI 0.888–1.000). Conclusions: In patients admitted to an ICU with septic shock, some initial coagulation test values can help identify those who will survive in the first week and then in the first month.

Does the type of fluid affect rapidity of shock reversal in an anaesthetized-piglet model of near-fatal controlled haemorrhage? A randomized study

BACKGROUND The optimal resuscitation fluid for the early treatment of severe bleeding patients remains highly debated. The objective of this experimental study was to compare the rapidity of shock reversal with lactated Ringer (LR) or hydroxyethyl starch (HES) 130/0.4 at the early phase of controlled haemorrhagic shock. To assess the influence of vascular permeability in this model, we measured plasma vascular endothelial growth factor (VEGF) levels during the experiment. METHODS Thirty-six anaesthetized and mechanically ventilated piglets were bled (<30 ml kg(-1)) to hold mean arterial pressure (MAP) at 40 mm Hg for more than 30 min and were resuscitated in two randomized groups: LR (n=14) or HES (n=14) at 1 ml kg(-1) min(-1) until MAP reached its baseline value of ±10%. MAP was maintained at its baseline value for 1 h. The time and fluid volume necessary to restore the baseline MAP value were measured. RESULTS The time to restore the baseline MAP value of ±10% was significantly lower in the HES group (P<0.001). During the initial resuscitation phase, the infused volume was 279 (119) ml in the HES group and 1011 (561) ml in the LR group (P<0.0001). During the stabilization phase, the infused volume was 119 (124) ml in the HES group and 541 (506) ml in the LR group. Biological data and plasma VEGF levels were similar between the groups. CONCLUSIONS Restoration of MAP was four times faster with HES than with LR in the early phase of controlled haemorrhagic shock. However, there was no evidence of increased vascular permeability.

Availability and practice of bedside ultrasonography in emergency rooms and prehospital setting: A French survey

INTRODUCTION The utility of bedside ultrasound (US) performed by emergency physicians has been proven for multiple purposes. There are no data about this technique in emergency departments (ED) in France. The primary objective is to determine the availability of ultrasound device (UD) in EDs and in prehospital settings in France. Minor objectives are to determine the number and type of UD, the most current applications of US and the factors correlated with availability of UDs in the setting of emergency medicine. METHODS This is a cross-sectional, descriptive, multicenter survey from December 2010 to June 2011, including all EDs and prehospital units in France. A questionnaire was sent by e-mail. Non-responders were contacted by telephone with one recall. RESULTS The response rate was 74% (327/440) for EDs and 73% (278/379) for prehospital units. A UD is available in 52% (171/327) (CI 95% [46; 58]) of EDs and in 9% (25/278) (CI 95% [5; 13]) of prehospital units. Among departments having no access to UDs, 29% of EDs and 12% of prehospital units have plans to implement emergency physician-performed US. The most common US applications are focused assessment with sonography for trauma and pleural exams. CONCLUSION Availability of UDs in French public hospital EDs is 52% and 9% in prehospital units. Despite the progressive expansion of the technique over the last years, bedside ultrasonography is not yet completely integrated in the physical examination of the patient in an emergency situation in France. A reassessment will be required to confirm the current trend of expansion.

Population pharmacokinetics of linezolid in critically ill patients on renal replacement therapy: comparison of equal doses in continuous venovenous haemofiltration and continuous venovenous haemodiafiltration

OBJECTIVES Few data are available to guide linezolid dosing during renal replacement therapy. The objective of this study was to compare the population pharmacokinetics of linezolid during continuous venovenous haemofiltration (CVVHF, 30 mL/kg/h) and continuous venovenous haemodiafiltration (CVVHDF, 15 mL/kg/h + 15 mL/kg/h). METHODS Patients requiring linezolid 600 mg iv every 12 h and CVVHF or CVVHDF were eligible for this prospective study. Seven blood samples were collected over one dosing interval and analysed by a validated chromatographic method. Population pharmacokinetic analysis was undertaken using Pmetrics. Monte Carlo simulations evaluated achievement of a pharmacodynamics target of an AUC from 0-24 h to MIC (AUC0-24/MIC) of 80. RESULTS Nine CVVHDF and eight CVVHF treatments were performed in 13 patients. Regimens of CVVHDF and CVVHF were similar. A two-compartment linear model best described the data. CVVHDF was associated with a 20.5% higher mean linezolid clearance than CVVHF, without statistical significance (P = 0.39). Increasing patient weight and decreasing SOFA score were associated with increasing linezolid clearance. The mean (SD) parameter estimates were: clearance (CL), 3.8 (2.2) L/h; volume of the central compartment, 26.5 (10.3) L; intercompartmental clearance constants from central to peripheral, 8.1 (12.1) L/h; and peripheral to central compartments, 3.6 (4.0) L/h. Achievement of pharmacodynamic targets was poor for an MIC of 2 mg/L with the studied dose. CONCLUSIONS During CVVHF and CVVHDF, there is profound pharmacokinetic variability of linezolid. Suboptimal achievement of therapeutic targets occurs at the EUCAST breakpoint MIC of 2 mg/L using 600 mg iv every 12 h.

Stroke volume optimization after anaesthetic induction: An open randomized controlled trial comparing 0.9% NaCl versus 6% hydroxyethyl starch 130/0.4

OBJECTIVE Postinduction hypotension during general anaesthesia could be corrected by a rapid cardiac preload optimization by fluid infusion. The type of fluid to be used in this context remains debated. The aim of our study was to compare the amount of fluid challenges required to optimize stroke volume after induction of anaesthesia with colloid (HES) or crystalloid (0.9% NaCl). DESIGN Open randomized prospective parallel-group study. PATIENTS AND METHODS Fifty-six adult patients scheduled to undergo orthopaedic surgery under general anaesthesia were randomly assigned to receive, either 0.9% NaCl (n=28), or HES (n=28). Cardiac preload optimization directed by oesophageal Doppler was performed after induction with fluid challenges of 250ml of solution until stroke volume (SV) no longer increased by 10%. Primary endpoint was: number of fluid challenges required to achieve SV optimization. Secondary endpoints were: number of patients responding to the first fluid challenge, proportion of patients requiring ephedrine and the ephedrine dose required to restore arterial pressure. RESULTS Percentages of responders were 61% and 63% in the 0.9% NaCl and HES groups, respectively. Number of fluid challenges necessary for SV optimization was not significantly different between 0.9% NaCl group and HES group (2 [1-2] versus 2 [1-2], P=0.33). Number of patients needing ephedrine, and well as the associated ephedrine dose, did not differ significantly. CONCLUSIONS Our study suggests that after induction, crystalloid and colloid expand the intravascular volume with equivalent efficacy immediately after administration and correct in a similar way the postinduction hypotension.

ISTH overt disseminated intravascular coagulation score in patients with septic shock: automated immunoturbidimetric soluble fibrin assay vs. D-dimer assay

J . -C . G R I S ,* J . L . FA I LL I E , § É . C OCHERY -NOUVELLON,* G. L I SSALDE-LAV IGNE * and J . -Y . LE FRAN T – *Haematology Laboratory, University Hospital, Nı̂mes, France The Haematology Laboratory, Faculty of Pharmacy and Biological Sciences; Research Unit 2992, University Montpellier 1; §Department of Medical Information, University Hospital, Nı̂mes; and –Central Intensive Care Unit, University Hospital, Nı̂mes, France