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Effective local anaesthesia is required to ensure pain-free dental procedures, but existing anaesthetics produce persistent soft tissue anaesthesia well beyond the average time for the painful treatment. This may result in lip and tongue biting in young children and the handicapped. The study reports the clinical attempts to usefully reduce this level of unwanted soft tissue anaesthesia by injecting into the anaesthetised tissues a potent vasodilating agent, phentolamine. Lignocaine and adrenaline is the standard dental local anaesthetic combination, with the adrenaline included to prolong the duration and depth of anaesthesia in the highly vascular perioral tissues. The added catecholamine prevents the anaesthetic from being rapidly absorbed from the injection site by producing intense vasoconstriction. An alternative dental local anaesthetic is the combination of prilocaine and felypressin. This also produces excessively long periods of soft tissue anaesthesia despite the vasoconstriction not being mediated through ?-adrenoceptors. Investigation of the clinical effects of reversing residual soft tissue anaesthesia produced by prilocaine and felypressin were thought worthwhile to enable the clinical safety of a potentially inappropriate drug combination to be assessed. It also produced comparative data for interpreting the catecholamine reponses to the routine lignocaine and adrenaline anaesthetics. Phentolamine is a short-acting and potent a-adrenoceptor blocking agent. The investigations confirm that a 2mg/ml phentolamine reversal solution, when injected after a 30 minute delay into the perioral tissues in the vicinity of the local anaesthetic solution, quickly reverses the vasoconstrictor effects of adrenaline in vivo. Maxillary infiltration soft tissue anaesthesia was reduced from 138.1 to 16.9 minutes (95% CI) and pulp anaesthesia from 40.3 to 4.8 minutes (95% CI). Inferior dental nerve block reversals were reduced from 160.3 to 17.3 minutes (95% CI) and pulp anaesthesia from 59.5 to 11.1 minutes (95% CI). Multiple injections of 6ml 2% lignocaine + 1:80,000 adrenaline were reversed with 3ml 2mg/ml phentolamine, and venous plasma local anaesthetic concentrations assayed using High Performance Liquid Chromatography (HPLC). No statistically significant increase in plasma lignocaine concentration (95% CI) was observed. Venous plasma lignocaine and catecholamine concentrations were measured after multiple perioral injections of 5.4ml 2% lignocaine with three differing adrenaline concentrations; 1:50,000, 1:80,000 and 1:100,000. No statistically significant difference in plasma lignocaine concentrations was noted between the groups. Plasma adrenaline concentrations were statistically raised in the 1:50,000 group (95% CI), but the noradrenaline concentrations showed no significant variation. The perioral injection of 3 ml 2mg/ml phentolamine reversal agent after the 30 minute delay produced increases in plasma lignocaine concentrations, with the weakest 1:100,000 adrenaline anaesthetic the most statistically significant (95% CI). The intense local vasodilatation was demonstrated to be effective against the nonadrenaline alternative anaesthetic prilocaine and felypressin, with a statistically significant rise in the venous plasma prilocaine concentration (95% CI). Plasma local anaesthetic concentrations failed to reach accepted levels of toxicity, and no adverse cardiovascular events were recorded. Venous plasma adrenaline concentrations were measured before and after dental surgical extractions under lignocaine and adrenaline or prilocaine and felypressin local anaesthesia. Venous plasma adrenaline concentrations were significantly raised in only half the cases, but the prilocaine and felypressin group showed a marked reduction in data scatter. Additional experiments attempting to reverse the soft tissue anaesthesia following injection of another dental local anaesthetic combination, mepivacaine and adrenaline, are presented as appendices. Plasma mepivacaine concentrations were not statistically raised compared with placebo. Venous plasma catecholamine concentrations were measured following perioral injection of 6ml 2% mepivacaine + 1:100,000 adrenaline, and after a 30 minute delay, with 3ml 2mg/ml phentolamine or placebo. No statistical difference was noted between the groups for adrenaline or noradrenaline concentrations, but a trend for the noradrenaline concentration to rise over the 2 hour test period was observed. No adverse local reactions or systemic cardiovascular changes were observed in any of the studies, implying that the prolonged soft tissue effects of dental local anaesthesia may be safely and rapidly reversed by injection of small increments of phentolamine into the adjacent perioral tissues. Such a facility will be useful in clinical dental practice where needlessly prolonged anaesthesia may have significant consequences to patients, such as lip biting in the handicapped.

The anaerobic digestion (AD) process is an established treatment for sewage sludge produced at municipal wastewater treatment plants. However, water utilities lack guidelines on the effect of upstream processes and AD operational conditions on the overall digestion performance. This is the first research that investigates the interactive effects of different process conditions to determine their overall impact on sludge AD performance. The research aims at determining the impact of physico-chemical properties on the biodegradability of feed sludge; quantifying the impact of multiple AD operational conditions on process performance and digestate quality and integrating the findings into a steady-state model to design, monitor and optimise the AD process of sewage sludge. The Box Behnken method was selected to design the experiment on multiple operational parameters in order to improve the estimation of the regression coefficients. Novel automatic pilot scale digesters were used to conduct uninterrupted digestion experiments for approximately 1,000 days. Together with these an array of lab scale and batch digestion systems were used to provide reference and monitor feed sludge biodegradability throughout the experimental programme. The results showed that measured sludge physico-chemical characteristics did not control bio-methane yield of primary sludge (PS), and PS produced similar biogas yield irrespective of the sludge source. By contrast, physico-chemical and operational parameters impacted the bio-methane yield of surplus activated sludge (SAS). These included sludge physico-chemical conditions (volatile solids content and elemental content) and upstream process conditions (solids retention time in the activated sludge plant). The operational parameters tested were PS:SAS ratio, digestion temperature and feed dry solids concentration (DS%). The results indicated a positive and significant interaction of high temperature and high DS% on specific biogas yield and pathogen removal, which could have significant implications in terms of process optimisation. In terms of reactor stability, the concentration of alkalinity and ammoniacal nitrogen were found primarily increasing with increasing DS% and SAS content, suggesting that operating the digester at relatively high load produces a more stable bio-chemical environment. It was concluded that AD of sewage sludge should be operated between 6-8% DS% at a temperature of 45oC in order to simultaneously produce a stable bio-chemical environment in the AD reactor, maximize biogas production and produce a conventionally treated sludge within a 16 day retention time. The produced steady-state model was used to determine that investments to upgrade an existing large scale sludge AD plant in the UK operating at sub-optimal conditions, could have a payback time of six years due to the benefits arising from displacement of imported electricity and fossil fuels.