Christopher Fry

BACKGROUND: Epidural analgesia is considered fundamental in enhanced recovery protocols (ERPs). However, its value in laparoscopic colorectal surgery is unclear. The aim of this study was to examine the effects of different analgesic regimens on outcomes following laparoscopic colorectal surgery in fluid-optimized patients treated within an ERP. METHODS: Ninety-nine patients were randomized to receive epidural, spinal or patient-controlled (PCA) analgesia. The primary endpoints were time until medically fit for discharge and length of hospital stay. Secondary endpoints included return of bowel function, pain scores, and changes in pulmonary function and quality of life. RESULTS: Ninety-one patients completed the study. The median length of hospital stay was 3.7 days following epidural analgesia, significantly longer than that of 2.7 and 2.8 days for spinal analgesia and PCA respectively (P = 0.002 and P < 0.001). There was also a slower return of bowel function with epidural analgesia than with spinal analgesia and PCA. Epidural analgesia did not offer better preservation of pulmonary function or quality of life, although pain scores were higher in the PCA group in the early postoperative period. CONCLUSION: Many of the outcomes in the epidural analgesia group were significantly worse than those in the spinal analgesia and PCA groups, suggesting that either of these two modalities could replace epidural analgesia.

BACKGROUND: Enhanced recovery programmes (ERPs) have been shown to reduce length of hospital stay (LOS) and complications in colorectal surgery. Whether ERPs have the same benefits in open liver resection surgery is unclear, and randomized clinical trials are lacking. METHODS: Consecutive patients scheduled for open liver resection were randomized to an ERP group or standard care. Primary endpoints were time until medically fit for discharge (MFD) and LOS. Secondary endpoints were postoperative morbidity, pain scores, readmission rate, mortality, quality of life (QoL) and patient satisfaction. ERP elements included greater preoperative education, preoperative oral carbohydrate loading, postoperative goal-directed fluid therapy, early mobilization and physiotherapy. Both groups received standardized anaesthesia with epidural analgesia. RESULTS: The analysis included 46 patients in the ERP group and 45 in the standard care group. Median MFD time was reduced in the ERP group (3 days versus 6 days with standard care; P < 0·001), as was LOS (4 days versus 7 days; P < 0·001). The ERP significantly reduced the rate of medical complications (7 versus 27 per cent; P = 0·020), but not surgical complications (15 versus 11 per cent; P = 0·612), readmissions (4 versus 0 per cent; P = 0·153) or mortality (both 2 per cent; P = 0·987). QoL over 28 days was significantly better in the ERP group (P = 0·002). There was no difference in patient satisfaction. CONCLUSION: ERPs for open liver resection surgery are safe and effective. Patients treated in the ERP recovered faster, were discharged sooner, and had fewer medical-related complications and improved QoL. REGISTRATION NUMBER: ISRCTN03274575 (http://www.controlled-trials.com).

Objective To determine whether suburothelial interstitial cells of the human bladder express gap junctions, and if so, to establish their extent and composition, using immunocytochemistry, confocal microscopy and electron microscopy. Materials and methods Bladder tissue was obtained at cystectomy; the tissue was: (i) frozen for cryosectioning and Northern blot analysis; (ii) fixed and embedded for standard thin‐section electron microscopy; and (iii) processed using low‐denaturation conditions in Lowicryl for immunogold‐label electron microscopy. Cryosections were immunofluorescently labelled using antibodies against connexins 43, 40 and 45, vimentin, desmin and c‐Kit ligand, and examined by confocal microscopy. Double labelling was used to determine the spatial relationship of labelling for connexin43 with that of vimentin and desmin. Thin‐section electron microscopy was used to investigate interstitial cell ultrastructure and permit unequivocal identification of gap junctions, and immunogold labelling of Lowicryl sections was applied to localize connexin43. Results Immunoconfocal microscopy showed prominent labelling for the gap junction protein, connexin43, in a suburothelial band of cells that was also strongly positive for vimentin. The connexin43/vimentin‐positive cells showed only weak labelling for desmin and c‐Kit ligand, and were immunonegative for connexins 40 and 45. Northern blotting showed a corresponding abundance of connexin43 transcript in the mucosal layer but not the detrusor layer of the bladder wall. Electron microscopy revealed abundant gap junctions, recognized by their pentalaminar structure, between the cell processes of interstitial cells in the suburothelial zone. That these interstitial cell gap junctions were the source of the connexin43 immunolabelling observed by immunoconfocal microscopy was confirmed by immunogold labelling in sections of Lowicryl‐embedded tissue examined by electron microscopy. Conclusion A network of interstitial cells, extensively linked by connexin43‐containing gap junctions, is located beneath the urothelium in human bladder. As gap junctions provide pathways for direct cell‐to‐cell communication, the interstitial cellular network may operate as a functional syncytium, integrating signals and responses in the bladder wall.

In sheep and calf ventricular bundles, increasing the internal calcium by increasing the frequency of voltage-clamping to plateau range potentials increased the time-independent outward current. This effect was more marked with higher [Ca]o, and was reduced if the Ca current blockers Verapamil or D 600 were used. 2. If the internal Ca was increased by the addition of cyanide and reduction of external sodium the outward current was also increased. The frequency-dependent increase in outward current also occurred in this Na-poor (12 mM) solution. 3. Tension measurement on the ventricular bundles showed that a Na-free solution with cyanide did not cause a contracture. On changing from Tyrode to a Na-free solution containing cyanide, and on changing back to Tyrode there was a potentiation of the twitch. 4. In Na-poor solution with cyanide, although no contracture was found, ECa was less positive, suggesting that under these circumstances Ca accumulates at the inner side of the membrane, but not around the myofibrils. 5. The prolongation of the action potential in Cl-free solution is frequency-dependent. A greater prolongation is seen at lower frequencies suggesting that Cl current is relatively more important for repolarization at lower frequencies of stimulation. 6. It is suggested that calcium at the inner side of the membrane sets the level of the background outward current. A feed-back mechanism on this basis is proposed for the control of the action potential duration. Various factors that could influence this basic mechanism are discussed.