Using the TI.VA algorithm to titrate the depth of general anaesthesia: a first-in-humans study.

Background: The dose of anaesthetic and opioid drugs must be continuously adjusted after the induction of general anaesthesia to maintain an adequate depth of anaesthesia. The TI.VA algorithm is a multiple-input/multiple-output algorithm designed to optimise the balance between anaesthetic and opioid concentrations during general anaesthesia. It applies vector analysis to a two-dimensional matrix to quantify any inadequacy of the depth of anaesthesia at any given moment and determine any drug dose adjustments required to achieve an adequate depth of anaesthesia. This study aimed to capture preliminary data on the performance and safety of the TI.VA algorithm during total i.v. anaesthesia in patients. Methods: This prospective study enrolled nine patients with breast cancer scheduled to undergo surgery. General anaesthesia was induced under manual control using propofol and remifentanil. Anaesthesia was guided using the TI.VA algorithm from skin incision until surgical resection was completed. The quality of anaesthesia was assessed through an analysis of performance errors. A bispectral index global score (GSBIS) <50 was considered an acceptable target for algorithm performance. Results: All nine procedures were completed without any adverse events and none of the patients recalled any intraoperative event. Overall, we analysed 3417 monitoring points corresponding to 285 min of surgery. All patients presented a GSBIS below the cut-off value of 50. Conclusions: The TI.VA algorithm provides adequate control of clinical anaesthesia. A more sophisticated prototype needs to be developed before the trial is expanded to include larger patient populations. Clinical trial registration: NCT05199883.

Methadone for postoperative analgesia: contribution of N-methyl-D-aspartate receptor antagonism: A randomised controlled trial.

BACKGROUND: Over the past number of years, N-methyl-D-aspartate (NMDA) inhibitory drugs, like ketamine, have been introduced as adjuvant treatments for postoperative acute pain, within a multimodal approach. A further extension of this strategy could be the use of opioids with NMDA receptor (NMDAr) antagonism activity for control of postoperative pain. Methadone has a unique pharmacodynamic profile: it is both a µ-agonist and an NMDAr-blocker. OBJECTIVE: We designed this study to investigate the precise contribution of NMDAr antagonism in methadone-induced analgesia. DESIGN: Single-centre, prospective, randomised, double-blind study. SETTING: National Cancer Center - Fondazione IRCCS Istituto Nazionale Tumori Milano; patients were recruited between March 2010 and June 2012. PATIENTS: Ninety-six patients scheduled for an open laparotomy for anterior resection of the rectum. INTERVENTIONS: We randomly assigned patients to four groups: 0-Mo (placebo and morphine), K-Mo [S(+)-ketamine and morphine], 0-Me (placebo and methadone), K-Me [S(+)-ketamine and methadone]. MAIN OUTCOME MEASURES: The primary end-point was the extent of mechanical static (punctuate) hyperalgesia to von Frey hair stimulation lateral to the surgical incision. RESULTS: Peri-incisional hyperalgesia was 8.4 cm (95% confidence interval, 1.5 to 15.41) lower in the treatment group (K-Me) compared with the control group (0-Mo) at 24 h after surgery (P = 0.02). No significant differences were observed between the groups at 48 h after surgery (P = 0.88). Both groups treated with methadone had significantly lower pain during rest and movement, as measured with a Numerical Rating Scale at 24 h. At 48 h, only the movement Numerical Rating Scale was significantly lower. No difference occurred in opioid consumption. CONCLUSION: Methadone provides effective control of acute postoperative pain, independently, by modulation of the hyperalgesia mechanism. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, no.: NCT01594047.

Serum soluble urokinase-type plasminogen activator receptor as a serum marker of inflammatory response that leads to tissue damage and surgical complication.

Unrestrained activation of the proteolytic systems in anastomotic tissue during repair has been implicated in the pathogenesis of anastomotic leakage. We hypothesized that this mechanism may promote an up-regulation of the urokinase-type plasminogen activator system and a spillover of soluble urokinase-type plasminogen activator receptor (suPAR) into blood. In this retrospective analysis patients with anastomotic leakage were compared with a group of matched uncomplicated patients. Anastomotic leakage complicated patients had significantly higher suPAR (p = 0.04) levels until day 3 after surgery. The area under the receiver-operating characteristic (ROC) for suPAR was higher than that CRP (0.874 vs. 0.836). Their analysis suggests the possible use of suPAR as serum marker to characterize the persistent inflammatory response that lead to tissue damage and surgical complication.