Marc Fischler

Closed-loop Coadministration of Propofol and Remifentanil Guided by Bispectral Index: A Randomized Multicenter Study

BACKGROUND:We have developed a proportional-integral-derivative controller allowing the closed-loop coadministration of propofol and remifentanil, guided by a Bispectral Index (BIS) monitor, during induction and maintenance of general anesthesia. The controller was compared with manual target-controlled infusion. METHODS:In a multicenter study, 196 surgical patients were randomly assigned to dual closed-loop or manual administration of propofol and remifentanil. Comparison between groups was evaluated by calculating a global score that characterized the overall performance of the controller including the percentage of adequate anesthesia, defined as BIS between 40 and 60, the median absolute performance error, and wobble. Secondary outcomes included occurrence of burst suppression ratio, time to tracheal extubation, and drug consumption. RESULTS:Eighty-three patients assigned to dual-loop control and 84 patients assigned to manual control completed the study. The global score and the percentage of time with BIS between 40 and 60 were better in the dual-loop group (26 ± 11 vs 43 ± 40, P < 0.0001; 82% ± 12% vs 71% ± 19%, P < 0.0001). Overshoot (BIS <40), undershoot (BIS >60), and burst suppression ratio were all significantly less common in the dual-loop group. Modifications to the propofol and remifentanil infusions were more frequent, and adjustments smaller in the dual-loop group. Remifentanil consumption was greater (0.22 ± 0.07 vs 0.16 ± 0.07 &mgr;g · kg−1 · min−1; P < 0.0001) and the speed to tracheal extubation was shorter (10 ± 4 vs 11 ± 5 minutes; P = 0.02) in the dual-loop group. CONCLUSION:The controller allows the automated delivery of propofol and remifentanil and maintains BIS values in predetermined boundaries during general anesthesia better than manual administration.

Intranasal drug delivery: an efficient and non-invasive route for systemic administration: focus on opioids.

Intranasal administration is a non-invasive route for drug delivery, which is widely used for the local treatment of rhinitis or nasal polyposis. Since drugs can be absorbed into the systemic circulation through the nasal mucosa, this route may also be used in a range of acute or chronic conditions requiring considerable systemic exposure. Indeed, it offers advantages such as ease of administration, rapid onset of action, and avoidance of first-pass metabolism, which consequently offers for example an interesting alternative to intravenous, subcutaneous, oral transmucosal, oral or rectal administration in the management of pain with opioids. Given these indisputable interests, fentanyl-containing formulations have been recently approved and marketed for the treatment of breakthrough cancer pain. This review will outline the relevant aspects of the therapeutic interest and limits of intranasal delivery of drugs, with a special focus on opioids, together with an in-depth discussion of the physiological characteristics of the nasal cavity as well as physicochemical properties (lipophilicity, molecular weight, ionisation) and pharmaceutical factors (absorption enhancers, devices for application) that should be considered for the development of nasal drugs.

Performance Evaluation of a Noninvasive Hemoglobin Monitoring Device

STUDY OBJECTIVE Hemoglobin measurement is a routine procedure, and a noninvasive point-of-care device may increase the quality of care. The aim of the present study is to compare hemoglobin concentration values obtained with a portable totally noninvasive device, the Masimo Labs Radical-7 Pulse CO-Oximeter, with the results obtained by the ADVIA 2120 in the laboratory. METHODS This was a prospective monocentric open trial enrolling patients consulting in the emergency department of a university hospital from June 16 to December 17, 2009. The main outcome measure was the agreement between both methods and evaluation of the percentage of potential decision error for transfusion. RESULTS Samples from 300 consecutive patients were assessed. Hemoglobin concentration could not be obtained with the new device for 24 patients. In others, the mean bias, the lower and the upper limits of agreement between the 2 methods, was 1.8 g/dL (95% estimated confidence interval [CI] 1.5 to 2.1 g/dL), -3.3 g/dL (95% CI -3.8 to -2.8 g/dL), and 6.9 g/dL (95% CI 6.4 to 7.4 g/dL), respectively. The intraclass correlation coefficient was 0.53 (estimated 95% CI 0.10 to 0.74). The number of potential errors about transfusion decision was 38 (13% of patients). The peripheral oxygen saturation and the true value of hemoglobin concentration were independently associated with the bias. CONCLUSION Results from this widely available noninvasive point-of-care hemoglobin monitoring device were systematically biased and too unreliable to guide transfusion decisions.

The Effects of Inhaled Nitric Oxide and Its Combination with Intravenous Almitrine on Pao2 During One-lung Ventilation in Patients Undergoing Thoracoscopic Procedures

The aim of this study was to assess whether hypoxemia during one-lung ventilation (OLV) can be prevented by inhaled nitric oxide (NO) (Part I) or by its combination with intravenous (IV) almitrine (Part II) in 40 patients undergoing thoracoscopic procedures. In Part I, 20 patients were divided into two groups: one received O2 (Group 1) and one received O2/NO (Group 2). In Part II, 20 patients were divided into two groups: one received O2 (Group 3) and one received O2/NO/almitrine (Group 4). In Groups 2 and 4, NO (20 ppm) was administered during the entire period of OLV, and almitrine was continuously infused (16 micro g [center dot] kg-1 [center dot] min-1) in Group 4. Arterial blood gases were measured during two-lung ventilation with patients in the supine position, after positioning in the lateral decubitus position, and then every 5 min for a 30-min period during OLV. During OLV, PaO2 values decreased similarly in Groups 1 and 2. After 30 min of OLV, the mean PaO2 values in Groups 1 and 2 were 132 +/- 14 mm Hg (mean +/- sem) and 149 +/- 27 mm Hg (not significant [NS]), and the PaO2 value was less than 100 mm Hg in four patients in Group 1 and five patients in Group 2. PaO2 values were greater in Group 4 than in Group 3 after 15 and 30 min of OLV. After 30 min of OLV, the mean PaO2 values were 146 +/- 16 mm Hg in Group 3 and 408 +/- 33 mm Hg in Group 4 (P < 0.001). PaO2 was less than 100 mm Hg during OLV (NS) in four patients in Group 3 and in no patient in Group 4. We conclude that NO inhalation alone has no effect on PaO2 evolution during OLV, although its combination with IV almitrine limits the decrease of PaO2 during OLV. This beneficial effect of NO/almitrine could be attributed to an improvement in ventilation-perfusion relationships. Implications: Decrease in oxygenation during one-lung ventilation is quite common. Our study showed that inhaled nitric oxide alone did not influence PaO2 evolution. We then tried adding intravenous almitrine to nitric oxide with amazingly good results on PaO2. This nonventilatory technique should be of great use during special thoracic acts, such as thoracoscopic procedures. (Anesth Analg 1997;85:1130-5)

Combined ultrasound and neurostimulation guidance for popliteal sciatic nerve block: a prospective, randomized comparison with neurostimulation alone.

BACKGROUND:Ultrasound imaging, an effective tool to localize peripheral nerves, may facilitate block performance. However, its usefulness during popliteal sciatic nerve block has not been assessed. METHODS:In this prospective, randomized, patient-blinded study, we compared the block time (as the primary end-point) of a popliteal sciatic nerve block with double-injection performed using anatomical landmarks and neurostimulation (NS group; n = 30) versus combined ultrasound and neurostimulation guidance (US-NS group; n = 30). Each block procedure was performed by a single operator. Correct needle placement was defined by a minimal stimulating current ≤0.5 mA, or, in the US-NS group, by mobilization of the nerve by the needle shaft even if the minimal stimulating current >0.5 mA. Ten milliliter levobupivacaine 0.5% was administered separately on the tibial and common peroneal nerves without needle adjustment to improve the spread of anesthetic in the US-NS group. All procedures were video-recorded, and a maximum of 7 min was allowed to perform the block. Successful block was defined as complete loss of cold sensation in the sciatic distribution and an inability to perform a plantar and dorsal flexion of the foot at 30 min. RESULTS:Five patients in the NS group and three in US-NS group were excluded from the study for prolonged procedure. Block time was not significantly different between groups. The number of needle passes was lower only for the detection of the first nerve in the US-NS group (1 [1–2] vs 2 [1–6]; P < 0.01). A greater success rate was observed at 30 min in the US-NS group (65% vs 16%; P < 0.001). CONCLUSIONS:Combined ultrasound and neurostimulation guidance does not decrease block time but increases the success rate of popliteal sciatic nerve block observed at 30 min.

A randomized, double-blinded comparison of intrathecal morphine, sufentanil and their combination versus IV morphine patient-controlled analgesia for postthoracotomy pain

We compared the analgesic effect of lumbar intrathecal (IT) 0.5 mg morphine (Group M, n = 10), 50 &mgr;g sufentanil (Group S, n = 10), and their combination (Group S-M, n = 10) given before general anesthesia and patient-controlled analgesia with IV morphine (Group C, n = 19) in a randomized, double-blinded study performed in patients undergoing thoracotomy. Pain visual analog scale (VAS) and morphine consumption were assessed for 24 h. In Group S-M the number of patients initially titrated with IV morphine was less than in group C (30 vs 84%, P < 0.05). Morphine requirement was higher in Group C (71 ± 30 mg) than in Groups S (46 ± 34 mg, P < 0.05), M (38 ± 31 mg, P < 0.05) and S-M (23 ± 16 mg, P < 0.01). VAS scores were significantly decreased during the first 0–11 postoperative h at rest and during the first 0–8 postoperative h on coughing in Groups M and S-M rather than in Group C. The incidence of side effects was infrequent except for urinary retention. Preoperative IT morphine or combined sufentanil and morphine could be given as a booster to achieve rapidly effective analgesia in the immediate postoperative period. IMPLICATIONS As compared with IV patient-controlled analgesia, intrathecal morphine or combined sufentanil and morphine provided superior postoperative pain relief both at rest (11 h) and on coughing (8 h) than did IV patient-controlled analgesia morphine alone. IV morphine requirement was decreased during the first postoperative day after posterolateral thoracotomy.

Assessment of systematic use of intraoperative transesophageal echocardiography during cardiac surgery in adults: A prospective study of 203 patients

OBJECTIVE To determine the usefulness of systematic intraoperative transesophageal echocardiography in a cardiac surgical unit. DESIGN Open prospective observational survey. SETTING University Hospital. PARTICIPANTS Consecutive adult patients (n = 203) undergoing elective or urgent cardiac operations. MEASUREMENTS AND MAIN RESULTS Pre-cardiopulmonary bypass imaging yielded unsuspected findings in 26 patients (12.8%) and changed the planned surgery in 22 patients (10.8%). Transesophageal echocardiography modified the diagnosis in eight patients (17%) operated on for mitral valvulopathy, in seven patients (15.5%) with aortic valvular disease, in four patients (4.6%) with coronary artery disease, in five patients operated on for thoracic aorta diseases regardless of their localization (18.5%), and in two miscellaneous cases. On the basis of the data obtained from the transesophageal echocardiography carried out at the end of cardiopulmonary bypass, an immediate reintervention was required in five cases (2.5%). CONCLUSIONS It is concluded that systematic intraoperative transesophageal echocardiography significantly affected decision making in this cardiac surgical unit. Its routine use in all cardiac surgical patients is recommended.

Feasibility of closed-loop titration of propofol and remifentanil guided by the spectral M-Entropy monitor.

Background: This randomized controlled trial describes automated coadministration of propofol and remifentanil, guided by M-Entropy analysis of the electroencephalogram. The authors tested the hypothesis that a novel dual-loop controller with an M-Entropy monitor increases time spent within predetermined target entropy ranges. Methods: Patients scheduled for elective surgery were randomly assigned in this single-blind study using a computer-generated list, to either dual-loop control using a proportional-integral-derivative controller or skilled manual control of propofol and remifentanil using target-controlled-infusion systems. In each group, propofol and remifentanil administration was titrated to a state entropy target of 50 and was subsequently targeted to values between 40 and 60. The primary outcome was the global score, which included the percentage of state entropy or response entropy in the range 40–60, the median absolute performance error and wobble. Data are presented as medians [interquartile range]. Results: Thirty patients assigned to the dual-loop group and 31 assigned to the manual group completed the study. The dual-loop controller was able to provide induction and maintenance for all patients. The Global Score of State Entropy was better maintained with dual-loop than manual control (25 [19–53] vs. 44 [25–110], P = 0.043), and state entropy was more frequently maintained in the range of 40–60 (80 [60–85] vs. 60 [35–82]%, P = 0.046). Propofol (4.1 [2.9–4.9] vs. 4.5 [3.4–6.3] mg · kg−1 · h−1) and remifentanil (0.18 [0.13–0.24] vs. 0.19 [0.15–0.26] &mgr;g · kg−1 · min−1) consumptions and the incidence of somatic side effects were similar. Conclusion: Intraoperative automated control of hypnosis and analgesia guided by M-Entropy is clinically feasible and more precise than skilled manual control.

Non-Invasive Measurement of Hemoglobin: Assessment of Two Different Point-of-Care Technologies

Background Measurement of blood hemoglobin (Hb) concentration is a routine procedure. Using a non-invasive point-of-care device reduces pain and discomfort for the patient and allows time saving in patient care. The aims of the present study were to assess the concordance of Hb levels obtained non-invasively with the Pronto-7 monitor (version 2.1.9, Masimo Corporation, Irvine, USA) or with the NBM-200MP monitor (Orsense, Nes Ziona, Israel) and the values obtained from the usual colorimetric method using blood samples and to determine the source of discordance. Methods and Findings We conducted two consecutive prospective open trials enrolling patients presenting in the emergency department of a university hospital. The first was designed to assess Pronto-7™ and the second NBM-200MP™. In each study, the main outcome measure was the agreement between both methods. Independent factors associated with the bias were determined using multiple linear regression. Three hundred patients were prospectively enrolled in each study. For Pronto-7™, the absolute mean difference was 0.56 g.L−1 (95% confidence interval [CI] 0.41 to 0.69) with an upper agreement limit at 2.94 g.L−1 (95% CI [2.70;3.19]), a lower agreement limit at -1.84 g.L−1 (95% CI [-2.08;-1.58]) and an intra-class correlation coefficient at 0.80 (95% CI [0.74;0.84]). The corresponding values for the NBM-200MP™ were 0.21 [0.02;0.39], 3.42 [3.10;3.74], -3.01 [-3.32;-2.69] and 0.69 [0.62;0.75]. Multivariate analysis showed that age and laboratory values of hemoglobin were independently associated with the bias when using Pronto-7™, while perfusion index and laboratory value of hemoglobin were independently associated with the bias when using NBM-200MP™. Conclusion Despite a relatively limited bias in both cases, the large limits of agreement found in both cases render the clinical usefulness of such devices debatable. For both devices, the bias is independently and inversely associated with the true value of hemoglobin. Trial Registration ClinicalTrials.gov NCT01321580 NCT01321593

Does monitoring bispectral index or spectral entropy reduce sevoflurane use

A decrease in volatile anesthetic consumption has been demonstrated using bispectral index (BIS), whereas data concerning spectral entropy are lacking. One hundred and forty adult patients scheduled for surgical procedures lasting more than 1 h were prospectively randomized to receive an anesthetic controlled either by BIS or by spectral entropy or solely by clinical variables. Anesthesia was induced with propofol and sufentanil. Sufentanil was infused continuously thereafter. Sevoflurane was administered in 1 L/min O2/N2O. The sevoflurane concentration was adjusted according to conventional clinical variables in the standard practice group, whereas the 40–60 interval was applied for the BIS and spectral entropy-guided groups. The sevoflurane vaporizer was weighed before and after anesthesia, and consumption was calculated. Groups were comparable for demographic data except for weight (heavier in the spectral entropy-guided group, P < 0.05). Compared with standard practice, patients with BIS or spectral entropy monitoring required 29% less sevoflurane (normalized sevoflurane consumption to the weights of the patients and to the durations of anesthesia; both P < 0.03) and a similar sufentanil dose. An unintended improvement in the standard practice group (positive bias) was observed. In conclusion, BIS and spectral entropy monitoring have the same sparing effect of sevoflurane.