L. Muller

Clinical relevance of pulse pressure variations for predicting fluid responsiveness in mechanically ventilated intensive care unit patients: the grey zone approach

IntroductionPulse pressure variation (PPV) has been shown to predict fluid responsiveness in ventilated intensive care unit (ICU) patients. The present study was aimed at assessing the diagnostic accuracy of PPV for prediction of fluid responsiveness by using the grey zone approach in a large population.MethodsThe study pooled data of 556 patients from nine French ICUs. Hemodynamic (PPV, central venous pressure (CVP) and cardiac output) and ventilator variables were recorded. Responders were defined as patients increasing their stroke volume more than or equal to 15% after fluid challenge. The receiver operating characteristic (ROC) curve and grey zone were defined for PPV. The grey zone was evaluated according to the risk of fluid infusion in hypoxemic patients.ResultsFluid challenge led to increased stroke volume more than or equal to 15% in 267 patients (48%). The areas under the ROC curve of PPV and CVP were 0.73 (95% confidence interval (CI): 0.68 to 0.77) and 0.64 (95% CI 0.59 to 0.70), respectively (P <0.001). A grey zone of 4 to 17% (62% of patients) was found for PPV. A tidal volume more than or equal to 8 ml.kg-1 and a driving pressure (plateau pressure - PEEP) more than 20 cmH2O significantly improved the area under the ROC curve for PPV. When taking into account the risk of fluid infusion, the grey zone for PPV was 2 to 13%.ConclusionsIn ventilated ICU patients, PPV values between 4 and 17%, encountered in 62% patients exhibiting validity prerequisites, did not predict fluid responsiveness.

The Comparative Electrophysiologic and Hemodynamic Effects of a Large Dose of Ropivacaine and Bupivacaine in Anesthetized and Ventilated Piglets

Ropivacaine is less potent and less toxic than bupivacaine. We administered these two local anesthetics in a cardiac electrophysiologic model of sodium thiopental-anesthetized and ventilated piglets. After assessing the stability of the model, bupivacaine (4 mg/kg) and ropivacaine (6 mg/kg) were given IV in two groups (n = 7) of piglets. No alteration in biological variables was reported throughout the study. Bupivacaine and ropivacaine similarly decreased mean aortic pressure from 99 ± 22 to 49 ± 31 mm Hg and from 87 ± 17 to 58 ± 28 mm Hg, respectively, and decreased the peak of the first derivative of left ventricular pressure from 1979 ± 95 to 689 ± 482 mm Hg/s and from 1963 ± 92 to 744 ± 403 mm Hg/s, respectively. Left ventricular end-diastolic pressure was similarly increased from 6 ± 5 to 9 ± 5 mm Hg and from 6 ± 4 to 12 ± 4 mm Hg, respectively. Bupivacaine and ropivacaine similarly lengthened the cardiac cycle length (R-R; from 479 ± 139 to 706 ± 228 ms and from 451 ± 87 to 666 ± 194 ms, respectively), atria His (from 71 ± 15 to 113 ± 53 ms and from 64 ± 6 to 86 ± 10 ms, respectively), and QTc (QTc = QT × R-R−0.5, Bazett formula; from 380 ± 71 to 502 ± 86 ms and from 361 ± 33 to 440 ± 56 ms, respectively) intervals. Bupivacaine altered to a greater extent the PQ (the onset of the P wave to the Q wave of the QRS complex) (from 97 ± 20 to 211 ± 60 ms versus from 91 ± 8 to 145 ± 38 ms, P < 0.05), QRS (from 58 ± 3 to 149 ± 34 ms versus from 60 ± 5 to 101 ± 17 ms, P < 0.05), and His ventricle interval (from 25 ± 4 to 105 ± 30 ms vs from 25 ± 4 to 60 ± 30 ms, P < 0.05) than ropivacaine. A 6 mg/kg ropivacaine dose induced similar hemodynamic alterations as 4 mg/kg bupivacaine. However, bupivacaine altered the variables of ventricular conduction (QRS and His ventricle) to a greater extent.

The intrathoracic blood volume index as an indicator of fluid responsiveness in critically ill patients with acute circulatory failure: a comparison with central venous pressure.

BACKGROUND: The intrathoracic blood volume index (ITBVI) and central venous pressure (CVP) are routinely used to predict fluid responsiveness in critically ill patients with acute circulatory failure (systolic blood pressure <90 mm Hg or vasopressor requirement). However, they have never been compared. METHODS: In this prospective interventional study, we included 35 (21 men) mechanically ventilated and sedated patients with acute cardiovascular failure requiring cardiac output measurement (transpulmonary thermodilution technique). Fluid responsiveness was defined as an increase in stroke index (cardiac output/heart rate/body surface area) ≥15%. Receiver operating characteristic curves were generated for ITBVI and CVP. RESULTS: Fluid challenge induced a stroke index increase ≥15% in 18 (51%) patients (responders). At baseline, no studied hemodynamic variables were different between responders and nonresponders. The areas under the receiver operating characteristic curves were 0.64 [95% CI: 0.46–0.80] for ITBVI and 0.68 [95% CI: 0.50–0.83] for CVP, without any statistical difference (P = 0.73). The best cut-off values for CVP and ITBVI were 9 mm Hg (sensitivity = 61%; specificity = 82%) and 928 mL · m−2 (sensitivity = 78%; specificity = 53%). CONCLUSION: ITBVI is similar to CVP in its ability to predict fluid responsiveness in critically ill patients with acute circulatory failure.

Standard dosing of amikacin and gentamicin in critically ill patients results in variable and subtherapeutic concentrations

Low peak plasma concentrations (Cmax) of amikacin and gentamicin are reported in intensive care unit (ICU) patients after administration of the first dose. The present study aimed to describe the proportion of ICU patients in whom an adequate Cmax was achieved throughout the course of therapy. Septic ICU patients with an indication for intravenous amikacin or gentamicin were eligible for inclusion in this single-centre observational study. The first and subsequent doses and the corresponding Cmax values were recorded. The target Cmax was ≥60mg/L for amikacin and ≥30mg/L for gentamicin. Amikacin and gentamicin plasma concentrations were available in 66 and 24 patients, respectively (59±17 years; 79±19kg; height 169±12cm; SAPS II score 46±19). Pulmonary, abdominal and urinary tract infections were diagnosed in 64 patients. Culture-positive infection was confirmed in 65 patients (72%). A target first Cmax was achieved in 17/90 patients (19%). For amikacin, the target Cmax was achieved in 16/66 patients (24%) after the initial dose. In the 50 remaining patients, a change in dosing was performed in 14 patients, leading adequate peak plasma level in 2 patients. For gentamicin, the targeted Cmax was achieved in only 1/24 patient (4%) after the initial dose and was never achieved after the third dose. In conclusion, standard dosing of amikacin or gentamicin led to adequate Cmax in only 19% of patients. Subtherapeutic Cmax were not significantly corrected after subsequent doses.

Impact of 30 mg/kg amikacin and 8 mg/kg gentamicin on serum concentrations in critically ill patients with severe sepsis

OBJECTIVES Low first-dose peak serum concentrations of amikacin and gentamicin are commonly reported in ICU patients. The present study aimed to assess whether 30 mg/kg amikacin or 8 mg/kg gentamicin achieved target concentrations in ICU patients with severe sepsis. PATIENTS AND METHODS Sixty-three ICU patients (Simplified Acute Physiology Score II = 43 ± 16) with severe sepsis and an indication for intravenous amikacin (n = 47) or gentamicin (n = 16) were included. The first (30 mg/kg amikacin; 8 mg/kg gentamicin) and subsequent doses and corresponding peak concentrations (30 min after the completion of an infusion) were recorded. French guideline target concentrations were ≥60 and ≥30 mg/L for amikacin and gentamicin, respectively. A target pharmacokinetic/pharmacodynamic ratio of 10 × MIC was also measured. RESULTS Pulmonary, abdominal and urinary tract infections were diagnosed in 56 patients. Infection was confirmed in 37 patients (59%). The targeted first-dose peak concentration was achieved in 37/63 patients (59%) [amikacin 36/47 (77%) and gentamicin 1/16 (6%)], and 59/63 patients (94%) achieved the pharmacokinetic/pharmacodynamic ratio using the MIC data that were available from 21 patients. However, the second dose of aminoglycoside was withheld because of high trough concentrations in nearly half of patients who did not have renal dysfunction. CONCLUSIONS In this study, 30 mg/kg amikacin and 8 mg/kg gentamicin led to target peak serum concentrations in 59% of patients.

Fluid management and risk factors for renal dysfunction in patients with severe sepsis and/or septic shock.

IntroductionThe causative role of new hydroxyethyl starch (HES 130/0.4) in renal dysfunction frequency (a > 50% increase in serum creatinine or need for renal replacement therapy (RRT)) remains debated. Using the database of a multicenter study focusing on patients with severe sepsis and septic shock, the present study aimed at identifying factors associated with the occurrence of renal dysfunction.MethodsAmong the 435 patients in a multicenter study of patients with severe sepsis and septic shock in 15 Southern French ICUs, 388 patients surviving after 24 hour, without a history of renal failure were included. Factors associated with renal dysfunction and RRT were isolated using a multivariate analysis with logistic regression.ResultsRenal dysfunction was reported in 117 (33%) patients. Ninety patients required RRT. Among study participants, 379 (98%) were administered fluids in the first 24 hours of management: HES 130/0.4 only (n = 39), crystalloids only (n = 63), or both HES 130/0.4 and crystalloids (n = 276). RRT was independently associated with the need for vasopressors and the baseline value of serum creatinine in the first 24 hours. Multivariate analysis indicated that male gender, SAPS II score, being a surgical patient, lack of decrease in SOFA score during the first 24 hours, and the interventional period of the study were independently associated with renal dysfunction. Mortality increased in the presence of renal dysfunction (48% versus 24%, P < 0.01).ConclusionsDespite being used in more than 80% of patients with severe sepsis and/or septic shock, the administration of HES 130/0.4 in the first 24 hours of management was not associated with the occurrence of renal dysfunction.

Hemodynamic and Cardiac Electrophysiologic Effects of Lidocaine–Bupivacaine Mixture in Anesthetized and Ventilated Piglets

Background The sensory blockade induced by a lidocaine–bupivacaine mixture combines the faster onset of lidocaine and the longer duration of bupivacaine. The current study compared the effects of large doses lidocaine (16 mg/kg), bupivacaine (4 mg/kg), and a mixture of 16 mg/kg lidocaine–4 mg/kg bupivacaine on hemodynamic and cardiac electrophysiologic parameters in anesthetized and ventilated piglets. Methods After carotid artery cannulation, a double micromanometer measured mean aortic pressure, left ventricular end diastolic pressure, and the first derivative of left ventricular pressure. Electrocardiogram recording and a bipolar electrode catheter measured RR, PQ, QRS, QTc, JTc, AH, and HV intervals. Lidocaine, bupivacaine, or the mixture was administered intravenously over 30 s, and studied parameters were measured throughout 30 min. Results Mean aortic pressure decreased in all groups (P < 0.05). The first derivative of left ventricular pressure was decreased in all groups (P < 0.001) but to a greater extent with the mixture compared with lidocaine (P < 0.04). RR, QTc, and JTc intervals were similarly increased in all groups (P < 0.05). In all groups, PQ, AH, HV, and QRS intervals were widened (P < 0.001). The lengthening of PQ was greater with bupivacaine (P < 0.02). The lengthening of AH was greater and delayed with bupivacaine compared with lidocaine (P < 0.03). The lengthening of HV and the widening of QRS were greater and delayed with bupivacaine (P < 0.01). The widening of QRS was greater with the mixture than with lidocaine (P < 0.01). Conclusions The alterations of ventricular conduction parameters are greater with 4 mg/kg bupivacaine than with a mixture of 16 mg/kg lidocaine–4 mg/kg bupivacaine, whereas the hemodynamic parameters are similarly altered.

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.