Ngai Liu

Lung transplantation from initially rejected donors after ex vivo lung reconditioning: the French experience

OBJECTIVES Only 15% of brain death donors are considered suitable for lung transplantation (LTx). The normothermic ex vivo lung perfusion technique is used to potentially increase the availability of high-risk lung donors. We report our experience of LTx with initially rejected donors after ex vivo lung reconditioning (EVLR). METHODS From April 2011 to May 2013, we performed EVLR for 32 pairs of donor lungs deemed unsuitable for transplantation and rejected by the 11 French lung transplant teams. After EVLR, lungs with acceptable function were transplanted. During the same period, 81 double-lung transplantations (DLTx) were used as controls. RESULTS During EVLR, 31 of 32 donor lungs recovered physiological function with a median PO2/FiO2 ratio increasing from 274 (range 162-404) mmHg to 511 (378-668) mmHg at the end of EVLR (P < 0.0001). Thirty-one DLTx were performed. The incidence of primary graft dysfunction 72 h after LTx was 9.5% in the EVLR group and 8.5% in the control group (P = 1). The median time of extubation, intensive care unit and hospital lengths of stay were 1, 9 and 37 days in the EVLR group and 1 (P = 0.17), 6 (P = 0.06) and 28 days (P = 0.09) in the control group, respectively. Thirty-day mortality rates were 3.3% (n = 1) in the EVLR group and 3.7% (n = 3) in the control group (P = 0.69). One-year survival rates were 93% in the EVLR group and 91% in the control group. CONCLUSIONS EVLR is a reliable and repeatable technique that offers a significant increase of available donors. The results of LTx with EVLR lungs are similar to those obtained with conventional donors.

Nitrous oxide does not produce a clinically important sparing effect during closed-loop delivered propofol–remifentanil anaesthesia guided by the bispectral index: a randomized multicentre study

BACKGROUND Nitrous oxide (N2O) offers both hypnotic and analgesic characteristics. We therefore tested the hypothesis that N2O administration decreases the amount of propofol and remifentanil given by a closed-loop automated controller to maintain a similar bispectral index (BIS). METHODS In a randomized multicentre double-blind study, patients undergoing elective surgery were randomly assigned to breathe 60% inspired N2O (N2O group) or 40% oxygen (AIR group). Anaesthesia depth was evaluated by the proportion of time where BIS was within the range of 40-60 (BIS40-60). The primary outcomes were propofol and remifentanil consumption, with reductions of 20% in either being considered clinically important. RESULTS A total of 302 patients were randomized to the N2O group and 299 to the AIR group. At similar BIS40-60 [79 (67-86)% vs 76 (65-85)%], N2O slightly decreased propofol consumption [4.5 (3.7-5.5) vs 4.8 (4.0-5.9) mg kg(-1) h(-1), P=0.032], but not remifentanil consumption [0.17 (0.12-0.23) vs 0.18 (0.14-0.24) µg kg(-1) min(-1)]. For the subgroups of men, at similar BIS40-60 [80 (72-88)% vs 80 (70-87)%], propofol [4.2 (3.4-5.3) vs 4.4 (3.6-5.4) mg kg(-1) h(-1)] and remifentanil [0.19 (0.13-0.25) vs 0.18 (0.15-0.23) µg kg(-1) min(-1)] consumptions were similar in the N2O vs AIR group, respectively. For the subgroups of women, at similar BIS40-60 [76 (64-84)% vs 72 (62-82)%], propofol [4.7 (4.0-5.8) vs 5.3 (4.5-6.6) mg kg(-1) h(-1), P=0.004] and remifentanil [0.18 (0.13-0.25) vs 0.20 (0.15-0.27) µg kg(-1) min(-1), P=0.029] consumptions decreased with the co-administration of N2O. CONCLUSIONS With automated drug administration titrated to comparable BIS, N2O only slightly reduced propofol consumption and did not reduce remifentanil consumption. There was a minor gender dependence, but not by a clinically important amount. Clinical trial registration This study was registered at ClinicalTrials.gov, number NCT00547209.

Feasibility of closed-loop co-administration of propofol and remifentanil guided by the bispectral index in obese patients: a prospective cohort comparison

BACKGROUND We used an automated bispectral index (BIS)-guided dual-loop controller to determine propofol and remifentanil requirements during general anaesthesia in obese and lean surgical patients. METHODS Obese patients, BMI>35 kg m(-2), and lean patients (<25 kg m(-2)) having laparoscopic procedures were prospectively evaluated in this multicentre single-blind study. The automated controller targeted BIS between 40 and 60 by adjusting propofol and remifentanil administration. Propofol and remifentanil consumptions were calculated using both total body weight (TBW) and ideal body weight (IBW). Results are expressed as medians (inter-quartile range). RESULTS Thirty obese [BMI=43 (40-49) kg m(-2)] and 29 lean [BMI=23 (21-25) kg m(-2)] patients completed the study. BIS was between 40 and 60 during 84 (69-91)% vs 85 (78-92)% of the anaesthetic time, P=0.46. The amount of propofol given during induction [1.2 (1.1-1.6) vs 1.3 (1.0-1.7) mg kg(-1), P=0.47] and maintenance [5.2 (4.1-6) vs 5.3 (4.7-6.4) mg kg(-1) h(-1), P=0.39] calculated using TBW was similar between the two groups. The dual-loop controller delivered half as much remifentanil to the obese patients during induction [1.0 (0.8-1.6) vs 2.2 (1.5-2.7) µg kg(-1), P<0.001] and maintenance [0.12 (0.07-0.16) vs 0.25 (0.17-0.29) µg kg(-1) min(-1), P<0.001] calculated using TBW. But when remifentanil consumption was calculated using IBW, the amounts were similar during induction at 2.2 (1.6-3.5) vs 2.0 (1.6-3.0) µg kg(-1) IBW, P=0.48, and during maintenance at 0.26 (0.16-0.34) vs 0.27 (0.18-0.33 ) µg kg(-1) min(-1), P=0.50. CONCLUSIONS The amount of propofol-remifentanil administered by the controller is consistent with current knowledge, propofol is best dosed using TBW whereas remifentanil is best dosed using IBW. CLINICAL TRIAL REGISTRATION NCT00779844.

Pilot study of closed-loop anaesthesia for liver transplantation.

BACKGROUND Automated titration of propofol and remifentanil guided by the bispectral index (BIS) has been used for numerous surgical procedures. Orthotopic liver transplantation (OLT) uniquely combines major changes in circulating volume, an anhepatic phase, and ischaemia-reperfusion syndrome. We assessed the behaviour of this automated controller during OLT. METHODS Adult patients undergoing OLT were included in this pilot study. Consumption of propofol and remifentanil was calculated for each surgery period (dissection, anhepatic, and liver reperfusion phases). Arterial blood samples were collected at several time points to allow comparison of actual with calculated propofol and remifentanil concentrations. Data are presented as median [25th and 75th percentiles] or percentage (95% confidence interval). RESULTS Thirteen patients were studied. System performance, defined as the percentage of time with BIS in the range 40-60, was 88% (86-94) of the total duration of anaesthesia. Propofol requirement was decreased during the anhepatic phase compared with the dissection phase (2.9 [1.9-5.0] mg kg(-1) h(-1) and 4.6 [3.5-8.1] mg kg(-1) h(-1); P<0.03) while remifentanil consumption was unchanged (0.11 [0.09-0.19] µg kg- (1) min(-1)). Bland-Altman analysis showed a weak concordance for propofol (bias of 0.7 µg ml(-1) and limits of agreement of -2.2 to +3.7 µg ml(-1)) and remifentanil (bias of 1.3 ng ml(-1) and limits of agreement -4.3 to +6.8 ng ml(-1)). No adverse events were reported during anaesthesia. CONCLUSIONS This pilot study indicates that automated titration of propofol and remifentanil guided by the BIS is feasible during OLT.

Closed-Loop Anesthesia Based on Neuromonitoring

This chapter reviews clinical studies concerning the automated administration of anesthetic agents guided by electrocortical activity. Studies have demonstrated the feasibility of automated control of propofol guided by the Bispectral Index for general anesthesia induction and maintenance. Automated control of propofol has been shown to outperform manual control and can be used for major surgery. At present, dual closed-loop control of propofol-remifentanil guided by Bispectral Index or Entropy is under evaluation. The automated titration of anesthetic drugs is no longer an esoteric research tool – it is now a tool for the clinicians of the future.

The feasibility of extubation in the operating room after bilateral lung transplantation in adult emphysema patients: an observational retrospective study

OBJECTIVES We introduced an extubation strategy for emphysema patients after bilateral lung transplantation. Patients who met the extubation criteria were extubated in the operating room (OR) followed by non-invasive ventilation, and the other patients were extubated in the intensive care unit (ICU). The primary objective was to determine the extubation rate. The secondary outcomes were to determine the factors allowing for extubation in the OR and the postoperative course. METHODS This study is a single-centre retrospective database analysis of 96 patients. Anaesthesia was performed using automated titration of total intravenous anaesthesia combined with thoracic epidural analgesia. Extubation criteria included arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, chest radiograph, oedema and haemodynamic stability. Data were compared using non-parametric tests and expressed as median (interquartile ranges) or number (%). RESULTS Fifty-three (55%) patients were extubated in the OR (the OR group) with 1 requiring reintubation and 43 (45%) patients were extubated in the ICU (the ICU group). Preoperative pulmonary hypertension, the requirement for intraoperative extracorporeal membrane oxygenation (ECMO), bleeding and ex vivo lung reconditioning donors were lower in the OR group. At the end of the procedure, the PaO2/FiO2 ratio was better [352 (289-437) vs 206 (144-357), P = 0.004), and the need for postoperative ECMO, mechanical ventilation duration, length of stay in the ICU [5 (4-7) vs 12 (8-20) days, P < 0.0001], Grade 3 primary graft dysfunction at 72 h [1 (2%) vs 10 (24%), P = 0.002] and 1-year mortality [5 (9%) vs 11 (26%) patients, P = 0.014] were lower in the OR group than in the ICU group. CONCLUSIONS Half of patients were extubated in the OR, and this strategy does not require additional ICU resources.

Closed-Loop or Automated Titration of Intravenous Anesthesia: Background, Science, and Clinical Impact

In 1950 the history of closed-loop intravenous anesthesia began in America. Mayo et al. reported the first clinical study of the use of a closed-loop controller on 50 patients allowing the automated titration of thiopental or ether guided by the electroencephalogram (EEG) activity. EEG activity was already reported as a surrogate measure of anesthetic drug effect, allowing the quantification of depth of anesthesia on seven levels and EEG was used as output for automated anesthetic titration. Thereafter it took several decades before new clinical studies with automated controllers were performed. The major milestone of closed-loop anesthesia occurred just around 2000, with the introduction of brain monitoring in clinical setting such as the Bispectral (BIS) index monitor (Covidien, Dublin, Ireland) associated with new short acting intravenous drugs with a short half-life (propofol or remifentanil) and new simple and powerful computers. To date several thousand patients worldwide have been anesthetized using different automated controllers. Despite an increasing number of clinical studies demonstrating the benefits of automated controllers, the administration of anesthetic agents during general anesthesia remains manual in routine care. However, two devices are commercially available; one was marketed for sedation during colonoscopy (Sedasys®, Jonhson and Jonhson, NJ, USA) and has been developed for non-anesthesiologists, the second device was developed for anesthesiologists (Concert-CL®, Veryark Technology, Guangxi, China) allowing the automated titration of propofol and rocuronium. But in 2016, the company of the Sedasys® has stopped to selling the device.