Peripheral nerve block anaesthesia and postoperative pain in acute ankle fracture surgery: the AnAnkle randomised trial.

BACKGROUND: Peripheral nerve blocks (PNBs) are increasingly popular in acute ankle fracture surgery but rebound pain may outweigh the benefits. The AnAnkle Trial was designed to assess the postoperative pain profile of PNB anaesthesia compared with spinal anaesthesia (SA). METHODS: The AnAnkle Trial was a randomised, two-centre, blinded outcome analysis trial. Eligible adults booked for primary ankle fracture surgery were randomised to PNB or SA. The PNBs were ultrasound-guided popliteal sciatic and saphenous blocks with ropivacaine and SAs were with hyperbaric bupivacaine. Postoperatively, all subjects received paracetamol, ibuprofen, and patient-controlled i.v. morphine for pain. The primary endpoint was 27 h Pain Intensity and Opioid Consumption (PIOC) score. Secondary endpoints included longitudinal pain scores and morphine consumption separately, and questionnaires on quality of recovery. RESULTS: This study enrolled 150 subjects, and the PNB success rate was >94%. PIOC was lower with PNB anaesthesia (median, -26.5% vs +54.3%; P<0.001) and the probability of a better PIOC score with PNB than with SA was 74.8% (95% confidence interval, 67.0-82.6). Pain scores and morphine consumption analysed separately also yielded a clear benefit with PNB, despite substantial rebound pain when PNBs subsided. Quality of recovery scores were similar between groups, but 99% having PNB vs 90% having SA would choose the same anaesthesia form again (P=0.03). CONCLUSIONS: PNB anaesthesia was efficient and provided a superior postoperative pain profile compared with SA for acute ankle fracture surgery, despite potentially intense rebound pain after PNB. CLINICAL TRIAL REGISTRATION: Clinicaltrialsregister.eu, EudraCT number: 2015-001108-76.

Uncoupling of vasopressin signaling in collecting ducts from rats with CBL-induced liver cirrhosis.

Vasopressin (AVP) stimulates collecting duct water reabsorption through cAMP-mediated membrane targeting and increased expression of the aquaporin-2 (AQP2) water channel. Rats with liver cirrhosis induced by common bile duct ligation (CBL) show decreased protein expression of AQP2 despite increased plasma concentrations of AVP. The present study was conducted to investigate possible mechanisms behind this uncoupling of AVP signaling. The rats were examined 4 wk after CBL or sham operation. The CBL rats had increased plasma AVP concentrations (CBL: 3.2 +/- 0.2 vs. sham: 1.4 +/- 0.4 pg/ml, P < 0.05) and reduced AQP2 (0.62 +/- 0.11) and phosphorylated AQP2 (0.50 +/- 0.06) protein expression compared with sham-operated rats. However, examination of subcellular AQP2 localization by immunohistochemistry showed unchanged plasma membrane targeting in CBL rats, indicating a sustained ability of AQP2 short-term regulation. In a separate series of animals, thirsting was found to normalize AQP2 expression, indicating that AVP uncoupling in CBL rats is a physiological compensatory mechanism aimed at avoiding dilutional hyponatremia. Studies on microdissected collecting ducts from CBL rats showed decreased cAMP accumulation in response to AVP stimulation. The presence of the nonspecific phosphodiesterase inhibitor IBMX normalized the cAMP accumulation, indicating that cAMP-phosphodiesterase activity is increased in CBL rats. However, in contrast to this, Western blotting showed a decreased expression of several phosphodiesterase splice variants. We conclude that CBL rats develop an escape from AVP to prevent the formation of dilutional hyponatremia in response to increased plasma AVP concentrations. The mechanism behind AVP escape seems to involve decreased collecting duct sensitivity to AVP as a result of increased cAMP-phosphodiesterase activity.