Richard Debon

Alveolar and Serum procalcitonin. Diagnostic and prognostic value in ventilator-associated pneumonia

Background The potential role of serum and alveolar procalcitonin as early markers of ventilator-associated pneumonia (VAP) and its prognostic value were investigated. Methods Ninety-six patients with a strong suspicion of VAP were prospectively enrolled. VAP diagnosis was based on a positive quantitative culture obtained via a mini–bronchoalveolar lavage of 103 colony-forming units/ml or more. Blood and alveolar samples were collected for procalcitonin measurement and analyzed for diagnostic and prognostic evaluation on days 0, 3, and 6. Sensitivity, specificity, positive likelihood ratio, and receiver-operating characteristic curves were analyzed to define ideal cutoff values and approach the decision analysis. Results Serum procalcitonin was significantly increased in the VAP group (n = 44) compared with the non-VAP group (n = 52): 11.5 ng/ml (95% confidence interval, 5.9–17.0) versus 1.5 ng/ml (1.1–1.9). A serum procalcitonin concentration greater than 3.9 ng/ml (best cutoff value) was considered positive for the VAP diagnosis (sensitivity, 41%; specificity, 100%). Serum procalcitonin was significantly increased in the non-survivors compared with the survivors for the VAP group: 16.5 ng/ml (95% confidence interval, 8.1–24.9) versus 2.9 ng/ml (1.2–4.7). The best cutoff value for serum procalcitonin of the nonsurvivors in the VAP group was 2.6 ng/ml (sensitivity, 74%; specificity, 75%; positive likelihood ratio, 2.96). Regarding VAP diagnosis and prognosis, no significant differences were found for alveolar procalcitonin in all groups. Conclusions Serum but not alveolar procalcitonin seems to be a helpful parameter in the early VAP diagnosis and an appropriate marker for predicting mortality.

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.

Oxidative Stress Status During Exposure to Propofol, Sevoflurane and Desflurane

We evaluated the circulating and lung oxidative status during general anesthesia established with propofol, sevoflurane, or desflurane in mechanically ventilated swines. Blood samples and bronchoalveolar lavage fluid (BAL) specimens were respectively performed via an internal jugular vein catheter and a nonbronchoscopic BAL for baseline oxidative activity measurements: malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPX). A 4-h general anesthesia was then performed in the three groups of 10 swine: the Propofol group received 8 mg · kg−1 · h−1 of IV propofol as the sole anesthetic; the Desflurane group received 1.0 minimum alveolar concentration of desflurane; and the Sevoflurane group received 1.0 minimum alveolar concentration of sevoflurane. We observed significantly larger levels of MDA in plasma and BAL during desflurane exposure than with the other anesthetics. We also observed smaller concentrations of circulating GPX and alveolar GPX. We found a significant decrease for MDA measurements in the plasma and the pulmonary lavage during propofol anesthesia. We also found larger values of GPX measurements in the serum and the pulmonary lavage. No significant changes were observed when animals were exposed to sevoflurane. No significant changes were found for circulating concentrations of SOD during exposure to all anesthetics. In this mechanically ventilated swine model, desflurane seemed to induce a local and systemic oxidative stress, whereas propofol and sevoflurane were more likely to have antioxidant properties.

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.

Chronopharmacology of intrathecal sufentanil for labor analgesia: daily variations in duration of action.

Background:The pharmacokinetic and pharmacodynamic characteristics of opioids vary throughout the day, as demonstrated for oral morphine in chronic pain. However, little is known about the chronobiology of intrathecal lipid soluble opioids used for labor analgesia. The aim of this prospective study was to determine whether the duration of action of intrathecally administered sufentanil is influenced by the time of administration. Methods:Ninety-one women in the first stage of labor were enrolled. Labor analgesia was first provided by 10 &mgr;g intrathecal sufentanil. The duration of action of intrathecal sufentanil was measured and analyzed by the cosinor method to determine periodic intraday variation. Results:Pain assessed by a visual analog score was not different among patients (70 ± 17 mm) before the injection of intrathecal sufentanil. Rhythm analysis revealed a mean (± SD) duration of analgesia (mesor) of 93.0 ± 3.8 min. A highly significant 12-h rhythm was found, with two peaks: One was near midnight (0.78 ± 0.6 h), and the other was near noon (12.78 ± 0.6 min) (P < 0.01). The amplitude of this 12-h component was 16.1 ± 5.5 min. Conclusions:The duration of intrathecal sufentanil analgesia exhibited a temporal pattern with 30% variations throughout the day period. The authors point out that the lack of consideration of chronobiological conditions in intrathecally administered analgesia studies can cause significant statistical bias. Further studies dealing with intrathecal opioids should consider the time of drug administration.

The Analgesic Effect of Sufentanil Combined with Ropivacaine 0.2% for Labor Analgesia: A Comparison of Three Sufentanil Doses

The combination of opioids with local anesthetics is commonly used for epidural labor analgesia. We examined whether increasing sufentanil in doses of 5, 10, and 15 &mgr;g prolonged the duration of labor analgesia produced by ropivacaine. One hundred healthy parturients in the first stage of labor who requested epidural analgesia were enrolled. Parturients were randomized to receive 12 mL ropivacaine 0.2% alone or with sufentanil 5 &mgr;g, sufentanil 10 &mgr;g, or sufentanil 15 &mgr; g. The duration of analgesia, pain score, degree of motor blockade (using a four-point Bromage scale), heart rate, blood pressure, respiratory rate, oxygen saturation, and incidence of nausea and pruritus were recorded. The mean duration of epidural analgesia was 96 ± 32 min for patients without sufentanil, 134 ± 27 min for Group 5 (p < 0.01 versus control), 135 ± 33 min for Group 10 (p < 0.01 versus control), 130 ± 33 min for Group 15 (p < 0.01 versus control) without differences among sufentanil groups. Between 30 and 90 min, the sufentanil groups (5 &mgr;g, 10 &mgr;g, and 15 &mgr;g) had lower pain scores than the control group (p < 0.01 versus control) but there were no differences among the sufentanil groups. No patient in any group had a Bromage score more than 1. No significant difference was found for opioid-related side effects. We conclude that 5–10 or 15 &mgr;g sufentanil induced a similar prolongation of analgesia when combined with ropivacaine 0.2% for initiation of labor analgesia. Implications We studied the effect of adding one of three possible sufentanil doses to epidural ropivacaine 0.2% for labor analgesia. Adding sufentanil increased the duration of analgesia but there was no advantage in adding more than 5 &mgr;g of sufentanil.

Effects of subhypnotic doses of propofol on gastric emptying in volunteers.

Background Drugs which accelerate gastric emptying (GE) decrease nausea and vomiting. This could contribute to the antiemetic potential of subhypnotic doses of propofol. On the contrary, subhypnotic doses of propofol used for sedation could decrease GE and thus favor regurgitation and pulmonary inhalation. Therefore, the aim of this study was to assess the effect of low-dose propofol infusion on GE. Methods On three separate occasions, 10 volunteers received either a propofol infusion at a rate set to achieve a target plasma concentration of 0.5 &mgr;g/ml or equivalent volumes of 10% Intralipid® or 0.9% saline. GE for solids was measured by using the octanoic acid breath test. An acetaminophen absorption technique measured the GE rate for liquids. Blood samples were assayed for acetaminophen and propofol. Breath samples were analyzed for 13CO2 concentration by isotope-ratio mass spectrometry. Carbon dioxide production (&OV0312;co2) was measured instead of calculated by indirect calorimetry. Sedation was evaluated by the Bispectral Index of the electroencephalogram. Results Propofol blood concentrations were 0.32 ± 0.20 and 0.45 ± 0.18 &mgr;g/ml at 60 and 165 min, respectively. These concentrations were not sedative. Propofol or its solvent did not modify GE for solids or liquids. In all groups, differences in GE were obtained if measured &OV0312;co2 was integrated in the formula instead of calculated &OV0312;co2 (P < 0.002). Conclusions Subhypnotic doses of propofol known to be antiemetic do not inhibit GE. These results suggest that the antiemetic properties of propofol are not peripheral and that propofol cannot be considered as a prokinetic agent. &OV0312;13co2 must be measured instead of calculated to accurately determine GE.

Le rémifentanil est une alternative efficace au propofol pour l’analgésie auto-contrôlée en endoscopie digestive

PURPOSE Unlike propofol, the self-administration of remifentanil for sedation in gastrointestinal endoscopies has never been evaluated formally. We wanted to compare the efficacy and tolerance of patient self-administration of remifentanil vs propofol during gastrointestinal endoscopy. METHOD This prospective randomized, single-blinded study, included 77 patients undergoing gastrointestinal endoscopy. Patients were divided into two groups: group R received remifentanil (5 microg.kg(-1).hr(-1) infusion, 25 microg boli, refractory period of five minutes) and group P received propofol (2 mg.kg(-1).hr(-1) infusion, 0.5 mg.kg(-1) boli, refractory period of ten minutes). A 1 mg.kg(-1) bolus of propofol was administered before the procedure began in cases of marked anxiety. Additional boli of 25 microg of remifentanil or 0.5 mg.kg(-1) of propofol were administered when patients complained during the refractory period. The evaluation targeted analgesic efficacy during the procedure and patient satisfaction. The degree of sedation during the procedure and the occurrence of adverse reactions were analyzed. RESULTS Patient satisfaction was high and comparable in both groups, with the number of awake and oriented patients being significantly higher in group R. Hemodynamic and respiratory tolerance was comparable in both groups, despite two episodes of desaturation in group R. The incidence of nausea was significantly higher in group R. CONCLUSIONS The self-administration of remifentanil for sedation during gastrointestinal endoscopies is as effective as the self-administration of propofol and can be offered to patients, especially when it is desirable that they remain conscious during the procedure.ObjectifA la différence du propofol, l’auto-administration de rémifentanil en sédation pour endoscopie digestive n’a jamais été évaluée dans la littérature. Nous avons voulu comparer l’efficacité et la tolérance de l’auto-administration de rémifentanil ou de propofol par le patient lors d’endoscopies digestives.MéthodeL’étude prospective, randomisée en simple aveugle, a été réalisée auprès de 77 patients devant bénéficier d’endoscopie digestive, répartis en deux groupes : groupe R = administration de rémifentanil (débit continu 5 μg·kg−1·h−1, bolus 25 μg, période réfractaire cinq minutes) et groupe P = administration de propofol (débit continu 2 mg·kg−1·h−1, bolus 0,5 mg·kg−1, période réfractaire dix minutes). Un bolus de 1 mg·kg−1 de propofol était administré avant le début de l’examen en cas d’anxiété importante. Des boli supplémentaires de 25 μg de rémifentanil ou de 0,5 mg·kg−1 de propofol étaient administrés en cas de plainte survenant en période réfractaire. L’évaluation a porté sur l’efficacité analgésique pendant l’examen et sur la satisfaction des patients. Le niveau de sédation pendant l’examen et la survenue d’effets indésirables ont été analysés.RésultatsLa satisfaction des patients était élevée et comparable dans les deux groupes, avec un nombre de patient réveillés et orientés significativement plus élevé dans le groupe R. La tolérance hémodynamique et respiratoire était comparable dans les deux groupes, malgré la survenue de deux épisodes de désaturation dans le groupe R. L’incidence des nausées était significativement plus importante dans le groupe R.ConclusionsL’auto-administration de rémifentanil en sédation pour endoscopie digestive est aussi efficace que l’auto-administration de propofol et peut être proposée notamment lorsque la perte de connaissance du patient n’est pas souhaitée.AbstractPurposeUnlike propofol, the self-administration of remifentanil for sedation in gastrointestinal endoscopies has never been evaluated formally. We wanted to compare the efficacy and tolerance of patient self-administration of remifentanil vs propofol during gastrointestinal endoscopy.MethodThis prospective randomized, single-blinded study, included 77 patients undergoing gastrointestinal endoscopy. Patients were divided into two groups: group R received remifentanil (5 μg·kg−1·hr−1 infusion, 25 μg boli, refractory period of five minutes) and group P received propofol (2 mg·kg−1·hr−1 infusion, 0.5 mg·kg−1 boli, refractory period of ten minutes). A 1 mg·kg−1 bolus of propofol was administered before the procedure began in cases of marked anxiety. Additional boli of 25 μg of remifentanil or 0.5 mg·kg−1 of propofol were administered when patients complained during the refractory period. The evaluation targeted analgesic efficacy during the procedure and patient satisfaction. The degree of sedation during the procedure and the occurrence of adverse reactions were analyzed.ResultsPatient satisfaction was high and comparable in both groups, with the number of awake and oriented patients being significantly higher in group R. Hemodynamic and respiratory tolerance was comparable in both groups, despite two episodes of desaturation in group R. The incidence of nausea was significantly higher in group R.ConclusionsThe self-administration of remifentanil for sedation during gastrointestinal endoscopies is as effective as the self-administration of propofol and can be offered to patients, especially when it is desirable that they remain conscious during the procedure.

[Remifentanil is an effective alternative to propofol for patient-controlled analgesia during digestive endoscopic procedures].

PURPOSE Unlike propofol, the self-administration of remifentanil for sedation in gastrointestinal endoscopies has never been evaluated formally. We wanted to compare the efficacy and tolerance of patient self-administration of remifentanil vs propofol during gastrointestinal endoscopy. METHOD This prospective randomized, single-blinded study, included 77 patients undergoing gastrointestinal endoscopy. Patients were divided into two groups: group R received remifentanil (5 microg.kg(-1).hr(-1) infusion, 25 microg boli, refractory period of five minutes) and group P received propofol (2 mg.kg(-1).hr(-1) infusion, 0.5 mg.kg(-1) boli, refractory period of ten minutes). A 1 mg.kg(-1) bolus of propofol was administered before the procedure began in cases of marked anxiety. Additional boli of 25 microg of remifentanil or 0.5 mg.kg(-1) of propofol were administered when patients complained during the refractory period. The evaluation targeted analgesic efficacy during the procedure and patient satisfaction. The degree of sedation during the procedure and the occurrence of adverse reactions were analyzed. RESULTS Patient satisfaction was high and comparable in both groups, with the number of awake and oriented patients being significantly higher in group R. Hemodynamic and respiratory tolerance was comparable in both groups, despite two episodes of desaturation in group R. The incidence of nausea was significantly higher in group R. CONCLUSIONS The self-administration of remifentanil for sedation during gastrointestinal endoscopies is as effective as the self-administration of propofol and can be offered to patients, especially when it is desirable that they remain conscious during the procedure.ObjectifA la différence du propofol, l’auto-administration de rémifentanil en sédation pour endoscopie digestive n’a jamais été évaluée dans la littérature. Nous avons voulu comparer l’efficacité et la tolérance de l’auto-administration de rémifentanil ou de propofol par le patient lors d’endoscopies digestives.MéthodeL’étude prospective, randomisée en simple aveugle, a été réalisée auprès de 77 patients devant bénéficier d’endoscopie digestive, répartis en deux groupes : groupe R = administration de rémifentanil (débit continu 5 μg·kg−1·h−1, bolus 25 μg, période réfractaire cinq minutes) et groupe P = administration de propofol (débit continu 2 mg·kg−1·h−1, bolus 0,5 mg·kg−1, période réfractaire dix minutes). Un bolus de 1 mg·kg−1 de propofol était administré avant le début de l’examen en cas d’anxiété importante. Des boli supplémentaires de 25 μg de rémifentanil ou de 0,5 mg·kg−1 de propofol étaient administrés en cas de plainte survenant en période réfractaire. L’évaluation a porté sur l’efficacité analgésique pendant l’examen et sur la satisfaction des patients. Le niveau de sédation pendant l’examen et la survenue d’effets indésirables ont été analysés.RésultatsLa satisfaction des patients était élevée et comparable dans les deux groupes, avec un nombre de patient réveillés et orientés significativement plus élevé dans le groupe R. La tolérance hémodynamique et respiratoire était comparable dans les deux groupes, malgré la survenue de deux épisodes de désaturation dans le groupe R. L’incidence des nausées était significativement plus importante dans le groupe R.ConclusionsL’auto-administration de rémifentanil en sédation pour endoscopie digestive est aussi efficace que l’auto-administration de propofol et peut être proposée notamment lorsque la perte de connaissance du patient n’est pas souhaitée.AbstractPurposeUnlike propofol, the self-administration of remifentanil for sedation in gastrointestinal endoscopies has never been evaluated formally. We wanted to compare the efficacy and tolerance of patient self-administration of remifentanil vs propofol during gastrointestinal endoscopy.MethodThis prospective randomized, single-blinded study, included 77 patients undergoing gastrointestinal endoscopy. Patients were divided into two groups: group R received remifentanil (5 μg·kg−1·hr−1 infusion, 25 μg boli, refractory period of five minutes) and group P received propofol (2 mg·kg−1·hr−1 infusion, 0.5 mg·kg−1 boli, refractory period of ten minutes). A 1 mg·kg−1 bolus of propofol was administered before the procedure began in cases of marked anxiety. Additional boli of 25 μg of remifentanil or 0.5 mg·kg−1 of propofol were administered when patients complained during the refractory period. The evaluation targeted analgesic efficacy during the procedure and patient satisfaction. The degree of sedation during the procedure and the occurrence of adverse reactions were analyzed.ResultsPatient satisfaction was high and comparable in both groups, with the number of awake and oriented patients being significantly higher in group R. Hemodynamic and respiratory tolerance was comparable in both groups, despite two episodes of desaturation in group R. The incidence of nausea was significantly higher in group R.ConclusionsThe self-administration of remifentanil for sedation during gastrointestinal endoscopies is as effective as the self-administration of propofol and can be offered to patients, especially when it is desirable that they remain conscious during the procedure.