Emmanuel Boselli

Steady-state plasma and intrapulmonary concentrations of cefepime administered in continuous infusion in critically ill patients with severe nosocomial pneumonia.

ObjectiveTo determine the steady-state plasma and epithelial lining fluid concentrations of cefepime administered in continuous infusion in critically ill patients with severe bacterial pneumonia. DesignProspective, open-label study. SettingAn intensive care unit and research ward in a university hospital. PatientsTwenty adult patients with severe nosocomial bacterial pneumonia on mechanical ventilation were enrolled. InterventionsAll subjects received a 30-min intravenous infusion of cefepime 2 g followed by a continuous infusion of 4 g over 24 hrs. The concentrations of cefepime in plasma and epithelial lining fluid were determined at steady state after 48 hrs of therapy with high performance liquid chromatography. Measurements and Main ResultsThe mean ± sd steady-state plasma and epithelial lining fluid concentrations of cefepime 4 g in continuous infusion were 13.5 ± 3.3 &mgr;g/mL and 14.1 ± 2.8 &mgr;g/mL, respectively, with a mean percentage penetration of cefepime into epithelial lining fluid of about 100%. ConclusionsThe administration of 4 g of cefepime in continuous infusion in critically ill patients with severe nosocomial pneumonia appears to optimize the pharmacodynamic profile of this &bgr;-lactam by constantly providing concentrations in excess of minimal inhibitory concentration of most of susceptible organisms over the course of therapy in both serum and epithelial lining fluid.

Clinical Assessment of the Ultrasonographic Measurement of Antral Area for Estimating Preoperative Gastric Content and Volume

BACKGROUND This prospective observational study aimed to assess the feasibility and performance of the ultrasonographic measurement of antral cross-sectional area (CSA) for the preoperative assessment of gastric contents and volume in adult patients and for the diagnosis of risk stomach (defined by the presence of solid particles and/or gastric fluid volume >0.8 ml/kg). METHODS A preoperative ultrasonographic measurement of the antral CSA was performed for each patient by a physician (L.B.) blinded to the history of the patient. Immediately after tracheal intubation, an 18-French multiorifice Salem tube was inserted and gastric contents were aspirated in five different patient positions; during this time, the patients epigastrium was massaged and the tube was moved backward and forward in the stomach. The relationship between the antral area and the volume of aspirated gastric contents was analyzed, as was the performance of ultrasonographic measurement of antral area for the diagnosis of risk stomach. RESULTS The measurement of antral CSA was performed on 180 of 183 patients. A significant positive relationship between antral CSA and aspirated fluid volume was found. The cutoff value of antral CSA of 340 mm(2) for the diagnosis of risk stomach was associated with a sensitivity of 91% and a specificity of 71%. The area under the receiver operating characteristic curve for the diagnosis of risk stomach was 90%. CONCLUSIONS The ultrasonographic measurement of antral CSA could be an important help for the anesthesiologist in minimizing the risk of pulmonary aspiration of gastric contents due to general anesthesia.

Alveolar concentrations of piperacillin/tazobactam administered in continuous infusion to patients with ventilator-associated pneumonia.

Objectives:To determine the steady-state serum and alveolar concentrations of piperacillin/tazobactam administered in continuous infusion to critically ill patients with ventilator-associated pneumonia and various degrees of renal failure. Design:Prospective comparative study. Setting:An intensive care unit and research ward in a university hospital. Patients:Forty patients with microbiologically documented ventilator-associated pneumonia. Interventions:Patients were randomized to receive piperacillin/tazobactam daily continuous infusions of 12/1.5 g or 16/2 g after a loading dose of 4/0.5 g. The serum and alveolar piperacillin/tazobactam concentrations were determined at steady-state with high performance liquid chromatography. Measurements and Main Results:The median (interquartile) serum and alveolar piperacillin concentrations were respectively 25.3 mg/L (23.1–32.6) and 12.7 mg/L (6.7–18.0) for 12/1.5 g/day, and 38.9 mg/L (32.9–59.6) and 19.1 mg/L (14.0–21.5), respectively, for 16/2 g/day in patients with no/mild renal failure. In patients with moderate/advance renal failure, the median (interquartile) serum and alveolar piperacillin concentrations were 102.4 mg/L (97.4–112.6) and 44.1 mg/L (33.4–48.3), respectively, for 12/1.5 g/day, and 135.3 mg/L (119.5–146.2) and 54.9 mg/L (45.2–110.3), respectively, for 16/2 g/day. Our results show great variability in piperacillin/tazobactam concentrations, with an alveolar percentage penetration of 40–50% for piperacillin and 65–85% for tazobactam and a negative association between serum or alveolar concentrations and creatinine clearance. Conclusions:A target piperacillin serum concentration of at least 35–40 mg/L is probably required to provide alveolar concentrations exceeding the susceptibility breakpoint for Gram-negative bacteria (16 mg/L) during ventilator-associated pneumonia. In patients with no/mild renal failure, a continuous daily dose of piperacillin/tazobactam 16/2 g allows reaching this target concentration, which might be not observed with 12/1.5 g/day. In patients with moderate/advanced renal failure, both dosages achieve serum concentrations far above the 35–40 mg/L threshold, suggesting that in that case, therapeutic drug monitoring should be performed in order to adjust the daily dose.

Pharmacokinetics and intrapulmonary diffusion of levofloxacin in critically ill patients with severe community-acquired pneumonia.

Objective:To determine the steady-state plasma and epithelial lining fluid concentrations of intravenous levofloxacin, 500 mg, administered once or twice daily in critically ill patients with severe community-acquired pneumonia. Design:Prospective, open-label study. Setting:An intensive care unit and a clinical pharmacokinetic laboratory in two university hospitals. Patients:Twenty-four adult patients with severe community-acquired pneumonia and receiving mechanical ventilation were enrolled. Interventions:All subjects received 1-hr intravenous infusions of 500 mg levofloxacin once or twice daily. The plasma and epithelial lining fluid levofloxacin concentrations were determined at steady-state after 2 days of therapy with high-performance liquid chromatography. Measurements and main results:The median (interquartile range [IQR]) plasma and epithelial lining fluid peak levofloxacin concentrations were 12.6 (IQR, 12.0–14.1) and 11.9 (IQR, 8.7–13.7) mg/L, respectively, in the once-daily group and 19.7 (IQR, 19.0–22.0) and 17.8 (IQR, 16.2–23.5) mg/L in the twice-daily group, showing a pulmonary percentage penetration of >100% in both groups. The median (IQR) total body exposures were 151 (IQR, 137–174) and 416 (IQR, 406–472) mg·hr/L, respectively, in the once-daily and twice-daily groups. Conclusions:Our results suggest that in critically ill patients who are receiving mechanical ventilation and have severe community-acquired pneumonia and creatinine clearance of >40 mL/min, the administration of 500 mg of intravenous levofloxacin once and twice daily allows for the exceeding of pharmacodynamic thresholds predictive of outcome (i.e., peak concentration to minimum inhibitory concentration ratio of >10 or area under concentration-time curve to minimal inhibitory concentration ratio of >125 hrs) both in serum and epithelial lining fluid for pathogens with minimum inhibitory concentration values of ≤1 mg/L and >1 mg/L, respectively.

Prospective observational study of the non-invasive assessment of immediate postoperative pain using the analgesia/nociception index (ANI)

BACKGROUND The analgesia/nociception index (ANI), a 0-100 non-invasive index calculated from heart rate variability, reflects the analgesia/nociception balance during general anaesthesia. The aim of this study was to evaluate the ANI in the assessment of immediate postoperative pain in adult patients undergoing general anaesthesia. METHODS Two-hundred patients undergoing scheduled surgery or endoscopy with general anaesthesia were included in this prospective observational study. Pain intensity was assessed using a 0-10 numerical rating scale (NRS) after arousal from general anaesthesia. Receiver-operating characteristic (ROC) curves were built to assess the performance of ANI to detect patients with NRS>3 and NRS ≥ 7 on arrival in the postoperative care unit. RESULTS A negative linear relationship was observed between ANI and NRS (ANI=-5.2 × NRS+77.9, r(2)=0.41, P<0.05). At the threshold of 57, the sensitivity and specificity of ANI to detect patients with NRS>3 were 78 and 80%, respectively, with a negative predictive value of 88%, corresponding to an area under the ROC curve (AUC) of 0.86. At the threshold of 48, the sensitivity and specificity of ANI to detect NRS ≥ 7 were 92 and 82%, respectively, with a negative predictive value of 99%, corresponding to a ROC curve AUC of 0.91. CONCLUSIONS A measurement of ANI during the immediate postoperative period is significantly correlated with pain intensity. The measurement of ANI appears to be a simple and non-invasive method to assess immediate postoperative analgesia.

High-volume haemofiltration with a new haemofiltration membrane having enhanced adsorption properties in septic pigs

BACKGROUND High-volume haemofiltration (HVHF) has been suggested as an adjuvant treatment of septic shock due to its capacities to remove from blood both pro- and anti-inflammatory mediators involved in the sepsis syndrome. Adsorption properties of some haemofiltration membranes are also interesting with this indication because inflammatory mediators are caught in the membrane itself. The aim of this study was to determine the haemodynamic and immunological effects of a new haemofiltration membrane, which has enhanced adsorption properties due to a special surface treatment, allowing the adsorption of endotoxins. METHODS We compared this membrane to a standard haemofiltration membrane both in vitro and in 20 sepsis-induced pigs, randomized in two groups. One group was haemofiltered with the treated membrane and the other with the standard haemofiltration membrane during 6-h HVHF sessions. RESULTS At the end of the experiment, mean +/- SD crystalloids requirements (5937 +/- 1588 versus 7587 +/- 1456 ml, P = 0.026), colloids requirements (1437 +/- 320 versus 1912 +/- 538 ml, P = 0.027), lactic acidosis (pH = 7.20 +/- 0.11 versus 7.10 +/- 0.07, P = 0.026) and pulmonary arterial hypertension (MPAP = 24 +/- 7 versus 34 +/- 8 mmHg, P = 0.008) were less pronounced when HVHF was performed with the treated membrane. In addition, mean +/- SD endotoxins levels were lower in the treated membrane group after 1 hour of HVHF (1.91 +/- 1.19 versus 11.07 +/- 10.64 EU/ml, P = 0.035). Cytokines levels were not different between groups except for IL-1beta, which was slightly lower in the treated membrane group. CONCLUSIONS The use of a membrane with enhanced adsorption properties during a 6-h HVHF session in septic pigs improves haemodynamics compared to a standard haemofiltration membrane. These results are probably due to an efficient endotoxins and cytokines adsorption. A human study using this membrane is now necessary to confirm these results.

Laryngeal injuries and intubating conditions with or without muscular relaxation: an equivalence study.

Purpose: The need for muscular relaxation to improve intubat-ing conditions and to reduce the incidence of laryngeal morbidity is still controversial. The aim of this study was to determine the incidence of symptomatic laryngeal injuries (SLI) and of acceptable intubating conditions (including both good and excellent conditions), both with and without cisatracurium during induction of anesthesia, along with moderate doses of remifen-tanil and propofol.Methods: In this prospective, randomized double-blind equivalence trial, the intubating conditions were compared in 130 ASA I or II female patients. All subjects received remifentanil 2 µg·kg−1iv and propofol 2.5 mg·kg−1iv, with either cisatracu-rium 0.15 mg·kg−1iv (group Cisatracturium), or saline (group Placebo). Tracheal intubating conditions were assessed with the Copenhagen Score. A systematic screening for postoperative hoarseness and sore throat was performed 24 and 48 hr after anesthesia, followed by a nasofibroscopic examination when laryngeal symptoms persisted at 48 hr.Results: Twenty-four hr after anesthesia, the incidence of postoperative hoarseness and sore throat in the Cisatracurium and Placebo groups was 26.5% and 21.5%, respectively, and 48 hr after anesthesia, the incidence was 7.8% and 6.1%, respectively (P=0.32 andP=0.50 between groups, respectively). In the clinically evaluable population, the incidence of SLI, assessed at 48 hr by nasofibroscopy, was equivalent in both groups, 1.6%vs 1.5% in group Placebo and group Cisatracurium, respectively (P<0.001 for equivalence test), as was the occurrence of acceptable intubating conditions (95.4%vs 100%,P<0.05 for equivalence test). However, the occurrence of excellent intu-bating conditions was more frequent in group Cisatracurium than in group Placebo (P=0.0003).Conclusion: Following induction of anesthesia with propofol and moderate-dose remifentanil, cisatracurium did not confer a higher rate of good-to-excellent conditions for tracheal intubation, nor did muscle relaxation with cisatracurium decrease the rate of SLI after tracheal intubation.RésuméObjectif: Le besoin de relaxation musculaire dans le but d’améliorer les conditions d’intubation et de réduire l’incidence de morbidité laryngée demeure controversé. L’objectif de cette étude était de déterminer l’incidence de lésions laryngées symptomatiques et des conditions d’intubation acceptables (incluant les conditions bonnes et excellentes), avec ou sans cisatracurium pendant l’induction de l’anesthésie, et combiné à des doses modérées de rémifentanil et de propofol.Méthode: Dans cette étude d’équivalence prospective, randomisée et à double insu, les conditions d’intubation ont été comparées chez 130 patientes ASA I ou II. Toutes les patientes ont reçu 2 µg·kg−1 de rémifentanil iv et 2.5 mg·kg−1 de propofol iv, avec soit 0,15 mg·kg−1 de cisatracurium iv (groupe Cisatracurium), soit une solution saline (groupe Placebo). Les conditions d’intubation trachéale ont été évaluées à l’aide de l’échelle de Copenhague. Un dépistage systématique de l’enrouement et des maux de gorge postopératoires a été réalisé 24 et 48 h après l’anesthésie, suivi d’un examen nasofibros-copique lorsque les symptômes laryngés persistaient à 48 h.Résultats: L’incidence d’enrouement et de maux de gorge postopératoires à 24 h était de 26,5 % et 21,5 % dans les groupes Cisatracurium et Placebo, respectivement. Quarante-huit heures après l’anesthésie, l’incidence était de 7,8 % et 6,1 %, respectivement (P=0,32 et P=0,50 entre les groupes, respectivement). Dans la population évaluable cliniquement, l’incidence de lésions laryngées symptomatiques, évaluée à 48 h par nasofibrosco-pie, était équivalente dans les deux groupes, soit 1,6 % et 1,5 % dans le groupe Placebo et le groupe Cisatracurium, respectivement (P<0,001 pour le test d’équivalence), tout comme l’occurrence avec des conditions d’intubation acceptable (95,4 % vs 100 %, P<0,05 pour le test d’équivalence). Toutefois, l’occurrence dans les situations où les conditions d’intubation étaient excellentes était plus fréquente dans le groupe Cisatracurium que dans le groupe Placebo (P=0,0003).Conclusion: À la suite d’une induction de l’anesthésie à l’aide de propofol et de rémifentanil en dose modérée, le cisatracurium n’a pas procuré un taux plus élevé de conditions bonnes à excellentes pour l’intubation trachéale ; en outre, la relaxation musculaire procurée par le cisatracurium n’a pas non plus réduit le taux de lésions laryngées symptomatiques après l’intubation trachéale.

Background infusion is not beneficial during labor patient-controlled analgesia with 0.1% ropivacaine plus 0.5 μg/ml sufentanil

BackgroundAlthough patient-controlled epidural analgesia (PCEA) during labor has been extensively studied in recent clinical trials, the role of a background infusion associated with self-administered boluses is still debated. The authors designed a study to assess whether the use of PCEA with or without background infusion could improve the comfort of parturients and their satisfaction during labor and delivery without affecting the total consumption of local anesthetics. MethodsOne hundred thirty-three laboring parturients requesting epidural analgesia administered via PCEA with a solution of 0.1% ropivacaine plus 0.5 &mgr;g/ml sufentanil were randomly assigned to four groups, according to the rate of background infusion used (0, 3, 6, and 9 ml/h). Local anesthetic requirements, maternal satisfaction, verbal pain scores, incidence of side effects, and outcome of labor were compared among groups. ResultsPatient demographics, labor characteristics, side effects, and Apgar scores were similar in each group. No significant differences were observed between groups in verbal pain scores during labor, number of supplemental boluses, or maternal satisfaction. A significantly greater overall total drug consumption with a 6-ml/h or a 9-ml/h background infusion (74 and 78 ml, respectively) was observed in comparison with PCEA without a background infusion (55 ml). A similar relation was observed for hourly use during both the first and the second stage of labor. ConclusionThe results of this study suggest that the use of a background infusion with PCEA during labor leads to a greater consumption of anesthetic solution without improving comfort and satisfaction of parturients. Moreover, not using a background infusion does not provide an increased incidence of supplemental boluses (which might cause problems in a busy unit) and allows for a substantial reduction in the cost of analgesia.

Chronobiology of epidural ropivacaine: variations in the duration of action related to the hour of administration.

Background A temporal pattern of the kinetics of local anesthetics is demonstrated in dental and skin anesthesia, with an important variation in the duration of action related to the hour of administration. The aim of this study is to determine whether the hour of injection influences the duration of epidurally administered ropivacaine during labor. Methods One hundred ninety-four women in the first stage of labor were assigned to one of four groups throughout the day period: group 1 (night: from 1:01 to 7:00 am), group 2 (morning: from 7:01 am to 1:00 pm), group 3 (afternoon: from 1:01 to 7:00 pm), and group 4 (evening: from 7:01 pm to 1:00 am). Each patient received 14 ml ropivacaine, 0.17%, epidurally, and analgesia duration was measured. Results Pain assessed by a visual analog score was not differ-ent among groups before the first injection of local anesthetic. Analgesia duration was greater in the diurnal period (group 2: 110 ± 25 min and group 3: 117 ± 23 min) compared with the nocturnal period (group 1: 94 ± 23 min and group 4: 91 ± 23 min) (P < 0.01). The largest intraday variation of analgesia duration among groups reached 28%. Conclusions Epidural analgesia duration exhibits a temporal pattern with important differences among diurnal and nocturnal phases. The authors emphasize that the lack of consideration of the chronobiologic conditions in epidural analgesia studies may create significant statistical bias. Future studies dealing with epidural local anesthetics should consider the time of drug administration.

Real-time detection of gastric insufflation related to facemask pressure-controlled ventilation using ultrasonography of the antrum and epigastric auscultation in nonparalyzed patients: a prospective, randomized, double-blind study.

Background:The authors sought to determine the level of inspiratory pressure minimizing the risk of gastric insufflation while providing adequate pulmonary ventilation. The primary endpoint was the increase in incidence of gastric insufflation detected by ultrasonography of the antrum while inspiratory pressure for facemask pressure-controlled ventilation increased from 10 to 25 cm H2O. Methods:In this prospective, randomized, double-blind study, patients were allocated to one of the four groups (P10, P15, P20, and P25) defined by the inspiratory pressure applied during controlled-pressure ventilation: 10, 15, 20, and 25 cm H2O. Anesthesia was induced using propofol and remifentanil; no neuromuscular-blocking agent was administered. Once loss of eyelash reflex occurred, facemask ventilation was started for a 2-min period while gastric insufflation was detected by auscultation and by real-time ultrasonography of the antrum. The cross-sectional antral area was measured using ultrasonography before and after facemask ventilation. Respiratory parameters were recorded. Results:Sixty-seven patients were analyzed. The authors registered statistically significant increases in incidences of gastric insufflation with inspiratory pressure, from 0% (group P10) to 41% (group P25) according to auscultation, and from 19 to 59% according to ultrasonography. In groups P20 and P25, detection of gastric insufflation by ultrasonography was associated with a statistically significant increase in the antral area. Lung ventilation was insufficient for group P10. Conclusion:Inspiratory pressure of 15 cm H2O allowed for reduced occurrence of gastric insufflation with proper lung ventilation during induction of anesthesia with remifentanil and propofol in nonparalyzed and nonobese patients. (Anesthesiology 2014; 120:326-34)