Séverine Lauwick

Breakdown of within- and between-network Resting State Functional Magnetic Resonance Imaging Connectivity during Propofol-induced Loss of Consciousness

Background:Mechanisms of anesthesia-induced loss of consciousness remain poorly understood. Resting-state functional magnetic resonance imaging allows investigating whole-brain connectivity changes during pharmacological modulation of the level of consciousness. Methods:Low-frequency spontaneous blood oxygen level-dependent fluctuations were measured in 19 healthy volunteers during wakefulness, mild sedation, deep sedation with clinical unconsciousness, and subsequent recovery of consciousness. Results:Propofol-induced decrease in consciousness linearly correlates with decreased corticocortical and thalamocortical connectivity in frontoparietal networks (i.e., default- and executive-control networks). Furthermore, during propofol-induced unconsciousness, a negative correlation was identified between thalamic and cortical activity in these networks. Finally, negative correlations between default network and lateral frontoparietal cortices activity, present during wakefulness, decreased proportionally to propofol-induced loss of consciousness. In contrast, connectivity was globally preserved in low-level sensory cortices, (i.e., in auditory and visual networks across sedation stages). This was paired with preserved thalamocortical connectivity in these networks. Rather, waning of consciousness was associated with a loss of cross-modal interactions between visual and auditory networks. Conclusions:Our results shed light on the functional significance of spontaneous brain activity fluctuations observed in functional magnetic resonance imaging. They suggest that propofol-induced unconsciousness could be linked to a breakdown of cerebral temporal architecture that modifies both within- and between-network connectivity and thus prevents communication between low-level sensory and higher-order frontoparietal cortices, thought to be necessary for perception of external stimuli. They emphasize the importance of thalamocortical connectivity in higher-order cognitive brain networks in the genesis of conscious perception.

Donation after cardio-circulatory death liver transplantation

The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ supply and following the request of potential DCD families. Since then, DCD organ procurement and transplantation activities have rapidly expanded, particularly for non-vital organs, like kidneys. In liver transplantation (LT), DCD donors are a valuable organ source that helps to decrease the mortality rate on the waiting lists and to increase the availability of organs for transplantation despite a higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of re-listing and re-transplantation and lower graft survival, which are obviously due to the inevitable warm ischemia occurring during the declaration of death and organ retrieval process. Experimental strategies intervening in both donors and recipients at different phases of the transplantation process have focused on the attenuation of ischemia-reperfusion injury and already gained encouraging results, and some of them have found their way from pre-clinical success into clinical reality. The future of DCD-LT is promising. Concerted efforts should concentrate on the identification of suitable donors (probably Maastricht category III DCD donors), better donor and recipient matching (high risk donors to low risk recipients), use of advanced organ preservation techniques (oxygenated hypothermic machine perfusion, normothermic machine perfusion, venous systemic oxygen persufflation), and pharmacological modulation (probably a multi-factorial biologic modulation strategy) so that DCD liver allografts could be safely utilized and attain equivalent results as DBD-LT.

Intravenous lidocaine infusion reduces bispectral index-guided requirements of propofol only during surgical stimulation

BACKGROUND I.V. lidocaine reduces volatile anaesthetics requirements during surgery. We hypothesized that lidocaine would also reduce propofol requirements during i.v. anaesthesia. METHODS A randomized controlled study of 40 patients tested the effect of i.v. lidocaine (1.5 mg kg(-1) then 2 mg kg(-1) h(-1)) on propofol requirements. Anaesthesia was maintained with remifentanil and propofol target-controlled infusions (TCI) to keep the bispectral index (BIS) around 50. Effect-site concentrations of propofol and remifentanil and BIS values were recorded before and after skin incision. Data were analysed using anova and mixed effects analysis with NONMEM. Two dose-response studies were then performed with and without surgical stimulation. Propofol TCI titrated to obtain a BIS around 50 was kept constant. Then patients were randomized into four groups: A, saline; B, 0.75 mg kg(-1) bolus then infusion 1 mg kg(-1) h(-1); C, 1.5 mg kg(-1) bolus and infusion 2 mg kg(-1) h(-1); and D, 3 mg kg(-1) bolus and infusion 4 mg kg(-1) h(-1). Lidocaine administration coincided with skin incision. BIS values and haemodynamic variables were recorded. Data were analysed using linear regression and two-way anova. RESULTS Lidocaine decreased propofol requirements (P<0.05) only during surgery. In the absence of surgical stimulation, lidocaine did not affect BIS nor haemodynamic variables, whereas it reduced BIS increase (P=0.036) and haemodynamic response (P=0.006) secondary to surgery. CONCLUSIONS The sparing effect of lidocaine on anaesthetic requirements seems to be mediated by an anti-nociceptive action.

Liver transplant donation after cardiac death : experience at the University of Liège

OBJECTIVE Donation after cardiac death (DCD) has been proposed to overcome in part the organ donor shortage. In liver transplantation, the additional warm ischemia time associated with DCD procurement may promote higher rates of primary nonfunction and ischemic biliary lesions. We reviewed the results of liver transplantation from DCD. PATIENTS AND METHODS From 2003 to 2007, we consecutively performed 13 controlled DCD liver transplantations. The medical records of all donors and recipients were retrospectively reviewed, evaluating in particular the outcome and occurrence of biliary complications. Mean follow-up was 25 months. RESULTS Mean donor age was 51 years, and mean intensive care unit stay was 5.4 days. Mean time between ventilation arrest and cardiac arrest was 9.3 minutes. Mean time between cardiac arrest and arterial flushing was 7.7 minutes. No-touch period was 2 to 5 minutes. Mean graft cold ischemia time was 295 minutes, and mean suture warm ischemia time was 38 minutes. Postoperatively, there was no primary nonfunction. Mean peak transaminase level was 2546 UI/mL. Patient and graft survival was 100% at 1 year. Two of 13 patients (15%) developed main bile duct stenosis and underwent endoscopic management of the graft. No patient developed symptomatic intrahepatic bile duct strictures or needed a second transplantation. CONCLUSIONS Our experience confirms that controlled DCD donors may be a valuable source of transplantable liver grafts in cases of short warm ischemia at procurement and minimal cold ischemia time.

End of life care in the operating room for non-heart-beating donors: organization at the University Hospital of Liège.

Non-heart-beating (NHB) organ donation has become an alternative source to increase organ supply for transplantation. A NHB donation program was implemented in our institution in 2002. As in many institutions the end of life care of the NHB donor (NHBD) is terminated in the operating room (OR) to reduce warm ischemia time. Herein we have described the organization of end of life care for these patients in our institution, including the problems addressed, the solution proposed, and the remaining issues. Emphasis is given to our protocol elaborated with the different contributors of the chain of the NHB donation program. This protocol specifies the information mandatory in the medical records, the end of life care procedure, the determination of death, and the issue of organ preservation measures before NHBD death. The persisting malaise associated with NHB donation reported by OR nurses is finally documented using an anonymous questionnaire.

Contribution of Donors After Cardiac Death to the Deceased Donor Pool: 2002 to 2009 University of Liege Experience

OBJECTIVE In this study, we have evaluated the organ procurement and transplantation activity from donors after cardiac death (DCD) at our institution over an 8-year period. Our aim was to determine whether this program influenced transplantation programs, or donation after brain death (DBD) activity. METHODS We prospectively collected our procurement and transplantation statistics in a database for retrospective review. RESULTS We observed an increasing trend in potential and actual DCD number. The mean conversion rate turning potential into effective donors was 58.1%. DCD accounted for 16.6% of the deceased donor (DD) pool over 8 years. The mean age for effective DCD donors was 53.9 years (range, 3-79). Among the effective donors, 63.3% (n = 31) came from the transplant center and 36.7% (n = 18) were referred from collaborative hospitals. All donors were Maastricht III category. The number of kidney and liver transplants using DCD sources tended to increase. DCD kidney transplants represented 10.8% of the DD kidney pool and DCD liver transplants made up 13.9% of the DD liver pool over 8 years. The DBD program activity increased in the same time period. In 2009, 17 DCD and 33 DBD procurements were performed in a region with a little >1 million inhabitants. CONCLUSION The establishment of a DCD program in our institution enlarged the donor pool and did not compromise the development of the DBD program. In our experience, DCD are a valuable source for abdominal organ transplantation.

A More Than 20% Increase in Deceased-Donor Organ Procurement and Transplantation Activity After the Use of Donation After Circulatory Death

BACKGROUND Organ procurement and transplant activity from controlled donation after circulatory death (DCD) was evaluated over an 11-year period to determine whether this program influenced the transplant and donation after brain death (DBD) activities. MATERIAL AND METHODS Deceased donor (DD) procurement and transplant data were prospectively collected in a local database for retrospective review. RESULTS There was an increasing trend in the potential and actual DCD numbers over time. DCD accounted for 21.9% of the DD pool over 11 years, representing 23.7% and 24.2% of the DD kidney and liver pool, respectively. The DBD retrieval and transplant activity increased during the same time period. Mean conversion rate turning potential into effective DCD donors was 47.3%. Mean DCD donor age was 54.6 years (range, 3-83). Donors ≥60 years old made up 44.1% of the DCD pool. Among referred donors, reasons for nondonation were medical contraindications (33.7%) and family refusals (19%). Mean organ yield per DCD donor was 2.3 organs. Mean total procurement warm ischemia time was 19.5 minutes (range, 6-39). In 2012, 17 DCD and 37 DBD procurements were performed in the Liege region, which has slightly >1 million inhabitants. CONCLUSIONS This DCD program implementation enlarged the DD pool and did not compromise the development of DBD programs. The potential DCD pool might be underused and seems to be a valuable organ donor source.

Effect of the transversus abdominis plane block on pain after laparoscopic inguinal hernia repair: 8AP5–5

Background and Goal of Study: The transversus abdominis plane (TAP) block is a new locoregional analgesia technique proposed to treat pain after abdominal surgery.1-3 We investigated the effect of TAP block on pain after laparoscopic inguinal hernia repair. Materials and Methods: With IEC approval and informed consent, 30 patients scheduled for preperitoneal laparoscopic inguinal hernia repair were included in this randomized double blind study. General anaesthesia (sevoflurane in O2:air) was used in all patients. After the induction of anaesthesia patients were randomly allocated in two groups (n=15 in each group): TAP block using McDonnell’s technique1 with 20 ml of levobupivacaine (LEVO) 0.375% Adr 1/200000 75 μg clonidine at each side or 20 ml saline (SAL) Adr 1/200000 75 μg clonidine at each side. Postoperative analgesia was standardized: iv piritramide titration the first h in the recovery room, then paracetamol 1 g/6 h and diclofenac 75 mg/12 h if necessary. Pain scores (100 mm VAS) at rest and during mobilisation during the first two postoperative days, consumption of piritramide, paracetamol, and time to first paracetamol request were recorded. Data (mean±SD) were analyzed by ANOVA, or Student t-test; P < 0.05 = statistically significant. Results and Discussion: All analgesic parameters were better in the LEVO group, but differences between groups did not reach statistical significance: pain scores at rest (Table) were lower (P = 0.1), piritramide consumption was less (1,7 ± 0.6 mg vs. 3.6 ± 0.9 mg, P = 0.1), and time to first paracetamol request was longer (11 ± 13 h vs. 7 ± 12 h, P = 0.1) in the LEVO group as compared the SAL group.

Liver Transplantation Is Feasible in Super-Obese Patients: A Case Report

Short- and long-term results of liver transplantation in morbidly obese patients may be impaired compared with the general transplant population. As a consequence, severe obesity has been considered to be a relative contraindication to liver transplantation in many centers. Surgically, liver transplantation in severe obesity may be challenging. Moreover, obesity may lead to an increased rate of early and late medical complications. Herein we have reported successful liver transplantation in a super-obese patient (body mass index, 55.1 kg/m(2)) who had developed terminal acute-on-chronic liver disease. In the first 6 months of follow-up, the patient underwent a severe diet that led to a significant weight loss reduction to a body mass index of 39 kg/m(2). This report of successful liver transplantation in a super-obese patient suggests that severe obesity should not be considered to be an absolute contraindication to liver transplantation.

Effects of intravenous clonidine on postoperative analgesia, sedation, and haemodynamic in morbidly obese patients undergoing laparoscopic gastric by-pass: 14AP4–10

Background and Goal of Study: Pelvic trauma followed by reconstructive surgery is associated with a high incidence of nerve damage and pain. The NMDA antagonist ketamine is not only effective in managing the symptoms of neuropathic pain [1] but is also morphine sparing in the first 24 hours after surgery [2]. We report on the use of patient controlled analgesia (PCA) morphine combined with ketamine for this patient group. Materials and Methods: We followed 132 in-patients who underwent reconstructive surgery for pelvic fractures; 59 received PCA morphine-plus-ketamine, both drugs 1mg/ml (1ml bolus; 5 minute lockout) for postoperative pain relief (Treatment group; TG), 73 historically matched patients received PCA morphine alone, same prescription (Control group; CG). Record was kept of patients’ demographic details, length of time and total morphine dose using PCA, effectiveness of pain control, side effects and number of Acute Pain Team contacts. The incidence, character and treatment of persistent post-PCA pain as well as overall patient experience was also recorded. Results and Discussion: Demographic details were similar in both groups. No statistically significant differences were observed between TG and CG with respect to duration and total morphine dose using PCA, effectiveness of pain control and patient experience, even when age or sex were investigated as confounders. Pruritus was commoner in CG 8% (6/73) compared with TG 3% (2/59) but the difference was not significant. Persistent post-PCA pain whilst in hospital was reported by 19% (14/73) patients in CG and was classified as neuropathic in 64% (9/14) of these patients, whilst 7% (4/59) patients in TG reported persistent post-PCA pain, none of whom were classified as having neuropathic pain. These differences did not achieve statistical significance. Conclusion(s): PCA morphine-plus-ketamine provided comparable analgesia to PCA morphine alone following reconstructive surgery for pelvic trauma without any increase in side effects. There was a trend towards a reduced in-hospital incidence of persistent postoperative neuropathic pain following PCA morphine-plus-ketamine but longer term follow up is needed. References: 1 Schmid R. Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes Pain 1999; 82: 111-125. 2 Bell RF, Dahl JB, Moore RA, Kalso E. Peri-operative ketamine for acute post-operative pain: a quantitative and qualitative systematic review (Cochrane review). Acta Anaesthesiologica Scandinavica 2005; 49: 1405-1428.