Bamigboye, Anthony Akinloye2012-07-112012-07-112012-07-11http://hdl.handle.net/10539/11668Ph.D., Faculty of Health Sciences, University of the Witwatersrand, 2011Caesarean section is the most widely performed major obstetric procedure. Even though regional block is often the anaesthesia of choice, general anaesthesia has its indications. Patients who deliver their babies by caesarean section under general anaesthesia deserve optimal pain management. Post-operative pain management is essentially multimodal, combining narcotics with non-steroidal anti-inflammatory and other interventions, including local anaesthetic infiltration in the wound or abdominal nerve blocks. Alleviating post-operative pain by the use of adjuvant local analgesia has been researched for several decades with conflicting reports. However, many obstetricians routinely infiltrate the wound with local anaesthetics, despite a lack of consensus on the technique or route of administration. To my knowledge, no reviews or metaanalysis of data have been done to support this practice. Most trials of local anaesthetics as an adjunct to pain relief have been carried out by using skin and subcutaneous wound infiltration. This technique of administration might have been responsible for producing conflicting results. Introducing a technique of anaesthetising all the layers of the anterior abdominal wound down to the peritoneum and comparing it to a placebo, may be one of a series of studies that can be undertaken to address the question of the efficacy of using local anaesthetics for post-caesarean section pain relief. The first part of this thesis is an experimental study design of a randomised clinical trial that was published in the official journal of the International Federation of Gynecology and Obstetrics (FIGO), the International journal of Obstetrics and Gynecology, in August 2008. This double-blind, placebo-controlled trial investigated the efficacy of routinely infiltrating the caesarean section wound and needle spraying, or infiltrating, the peritoneum with the local 13 anaesthetic agent, ropivacaine. The objective of the trial was to assess the effect of this intervention on post-operative pain and the need for opioid use in the immediate post caesarean section period in women with planned surgical deliveries. The technique of infiltrating all layers of the abdominal wound was an innovation as compared to the subcutaneous and skin infiltration that has traditionally been carried out. The inclusion of the breached peritoneal surfaces was to address the deep pain of peritoneal injury that might occur from abdominal surgery. The results of this trial, using ropivacaine wound infiltration into all layers of the anterior abdominal wall, as adjuvant post-operative analgesia in elective caesarean sections for single uncomplicated pregnancies at term, showed a reduction in the need for narcotic analgesics and a reduction in the occurrence of severe post-operative pain in women undergoing general anaesthesia. There appears to be no recommended dose of local anaesthetics for a caesarean section wound infiltration and peritoneal application therefore, for the trial, we were concerned about exceeding the safety limits. The risk of serum toxicity from peritoneal application of the local anaesthetic might be high as the absorption of drugs and fluids through the peritoneum is generally optimal. Hence, for the clinical trial, we adopted the dose used for brachial plexus block. If this baseline dose produced a serum concentration that was within the safety margin (less than toxic concentration); a dose finding trial of lesser concentration could be embarked upon. This motivated the need for the serum concentration study published in the International journal of Obstetrics and Gynaecology in January 2009. Using high performance liquid chromatography in 71 serum samples at different time intervals, the maximum concentration of ropivacaine using a dosage of 225mg by infiltration through all layers of the anterior abdominal wall incision, including the peritoneum at caesarean section was 1553 (SD 793) ug/L. This falls within the safety range in humans, and below levels reached following brachial plexus block. 14 The last part of the thesis combines all suitable randomised trials, including the clinical trial described above, in a systematic review, to advise health care providers on the role of adjuvant local anaesthetic infiltration in caesarean section pain relief. The decision to include the author‘s trial was made by an independent Cochrane reviewer based on strictly objective criteria. The systematic review of the effects of this health care intervention of local anaesthetic infiltration in caesarean section wounds was edited by the Pregnancy and Childbirth group of the Cochrane collaboration, Liverpool, United Kingdom. The review addresses a clearly defined question and explains how studies for the review were located, selected and excluded. It gives details of the search strategy used, explains how data were collected from studies, how missing data were handled and how study quality was assessed. In twenty trials involving 1150 patients, it concludes that local anaesthetic wound infiltration and abdominal nerve blocks as adjuncts to regional and general anaesthesia, were of benefit in caesarean section by reducing opioid consumption. Non-steroidal anti-inflammatory drugs as an adjuvant conferred additional pain relief. The importance and relevance of the systematic review, which was published in two peer review journals, can be inferred by the interest which it has generated in the press worldwide. This may provide indirect evidence of its potential to change clinical practice. A PhD thesis, inter alia, needs to contribute to the advancement of knowledge. The potential of the systematic review to achieve this was recognised by Faculty 1000, ‗a revolutionary literature awareness service that identifies and evaluates the most important articles published in Medicine based on the recommendations of a Faculty of over 2000 peer-nominated leading researchers and clinicians‘, by way of an award. Pain management, in the modern medical practice, is a sub-specialty that falls within the domain of anaesthetists. A thesis on the subject might appear not to be a primary responsibility of an obstetrician. However, after the anaesthetist has completed the broader duty of advising on post caesarean section pain management, it is the obstetrician who is faced with further augmenting or modifying pain relief prescribed by the anaesthetists. In addition, if wound infiltration is to be employed, the obstetrician who performs the procedure is better placed to administer the intervention intra-operatively. Based on this premise, it is appropriate that an obstetrician conducted studies on local anaesthetic as an adjunct to caesarean section pain relief.enThesis