BJOG Exchange
With regards to the use of rescue analgesia, the details can be found in Table S4 of the supporting information for the original article. One hundred and ninety-eight women (82%) in the diamorphine group, compared with 195 women (81%) in the pethidine group, received Entonox as rescue analgesia post-randomisation (P = 0.98). Fifty-nine (24%) in the diamorphine group and 42 (18%) in the pethidine group received epidurals post-randomisation (P = 0.07). The fact that over 80% of women in either group needed Entonox to supplement analgesia confirmed our conclusion that both analgesics gave modest pain relief. Furthermore, more than 84% of women from both groups reported verbally moderate to severe pain intensity over the first 3 hours of analgesia. Finally, we were asked to comment on the use of a 1-cm difference in visual analogue score (VAS) as the basis for the sample size calculation, and its subsequent labelling as a modest effect size. A detailed description of the rationale for choosing a 1-cm difference is provided in the published protocol for the study.2 The primary aim of our trial was to repeat what we suspected was an underpowered trial, which concluded that diamorphine was a better analgesic with reduced side effects when compared with pethidine.3 We have also explained in the discussion section of our paper the rationale for labelling a 1-cm difference in VAS as a modest difference.1 We believe it is difficult to describe the difference any other way, when the majority of women receiving either diamorphine or pethidine described their pain as being moderate to severe in intensity. As noted above, the following additional Supporting Information may be found in the online version of our article: Table S1. Baseline characteristics – outcome variables. Table S2. Maternal and neonatal outcomes. Table S3. Secondary outcome measures – Maternal pain variables. Table S4. Secondary outcome measures – Other maternal variables.
Table S5. Secondary outcome measures – Neonatal variables. Table S6. Mode of delivery. Appendix S1. IDvIP Trial: Data Collection Sheet. & References 1 Wee MYK, Tuckey JP, Thomas PW, Burnard S. A comparison of intramuscular diamorphine and intramuscular pethidine for labour analgesia: a two centre randomised blinded controlled trial. BJOG 2014;121:447–56. 2 Wee MYK, Tuckey JP, Thomas P, Burnard S. A two-centre randomised double-blind controlled trial comparing intramuscular diamorphine and intramuscular pethidine for labour analgesia. BMC Pregnancy Childbirth 2011;11:51. [www.biomedcentral.com/14712393/11/51]. Accessed 2 July 2014. 3 Fairlie FM, Marshall L, Walker JJ, Elbourne D. Intramuscular opioids for maternal pain relief in labour: a randomised controlled trial comparing pethidine with diamorphine. Br J Obstet Gynaecol 1999;106:1181–7.
MYK Wee,a JP Tuckey,b PW Thomasc & S Burnardb a
Poole Hospital NHS Foundation Trust, Poole, UK bRoyal United Hospital, Bath, UK c Clinical Research Unit,School of Health and SocialCare, Bournemouth University, Bournemouth, UK Accepted 11 June 2014. DOI: 10.1111/1471-0528.12986
There must be more to surgical wound infection prevention than antibiotic prophylaxis alone
Sir, We read with interest the article by Brummer et al.1 regarding their investigations into establishing an optimum antibiotic prophylaxis for hysterectomy. We share the interest that the FINHYST study has in trying to establish a methodology for reducing postoperative infectious morbidity. The benefit of antibiotic prophylaxis for hysterectomy was first demonstrated three decades ago.2 And, broadly speaking, antibiotic prophylaxis reduces the incidence of postoperative infection by half. But despite giving antibiotics – and
ª 2014 Royal College of Obstetricians and Gynaecologists
using appropriate antiseptic skin preparation – postoperative infection still occurs. This carries substantial cost implications and much patient dissatisfaction. As antibiotic prophylaxis has failed to abolish postoperative infections, one has to wonder whether other strategies need to be established. Peri-operative hypothermia is known to be a potent risk factor for developing wound infections,3 as well as being a risk factor for increased bleeding. Conversely, keeping patients warm during the peri-operative period reduces the risk of infections.4 Peri-operative hypothermia is easily preventable with the use of patient warming devices, which are widely available and relatively inexpensive. As well as maintaining normothermia, it makes sense to avoid hypothermia at the site of surgical incision. Hypothermia at the site of surgical incision can readily occur with some skin preparation agents. Because of the latent heat of vaporisation, ethanol-based skin prep causes a marked hypothermia at the site where it is applied. We measured the skin temperature of the ventral surface of the forearm of five volunteers in an operating theatre. The average skin temperature was 35.5°C. Alcohol-based skin prep (comprising 96% denatured ethanol) was applied and allowed to dry. The skin temperature was re-measured and on average was 27°C. The skin temperature remained at an average of 27°C 5 min later, and at 10 minutes no subject had a skin temperature above 30°C. For many years the management of breast cancer was confined to operative procedures, with depressingly poor results. Adjuvant treatments of radiotherapy, chemotherapy and anti-estrogen agents were introduced with superb results. Likewise, we feel the synergistic effect of adjuvant measures such as patient warming and avoiding inadvertent hypothermia at the site of surgical incision coupled with prophylactic antibiotics is what may well make
1575
BJOG Exchange
postoperative surgical infection a much rarer thing than it currently is. Certainly it is an avenue to explore. & References 1 Brummer T, Heikkinen A, Jalkanen J, Fraser J, M€ akinen J, Tom as E, et al. Antibiotic prophylaxis for hysterectomy, a prospective cohort study: cefuroxime, metronidazole, or both? BJOG 2013;120:1269–1276. 2 Cartwright P, Pittaway D, Jones H, Entman S. The use of prophylactic antibiotics in obstetrics and gynecology. A review. Obstet Gynecol Surv 1984;39:537–554. 3 Seamon MJ, Wobb J, Gaughan JP, Kulp H, Kamel I, Dempsey DT. The effects of intraoperative hypothermia on surgical site infection: an analysis of 524 trauma laparotomies. Ann Surg 2012;255:789–795. 4 Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization Study of Wound Infection and Temperature Group. N Engl J Med 1996;334:1209–1215.
MJ Dickson,a R Yakubb & K Cheungb a
Wayside, Cheshire, UK bRoyal Oldham Hospital, Oldham, Lancashire, UK
Accepted 24 September 2013. DOI: 10.1111/1471-0528.12644
Authors’ reply Sir, We thank Drs Dickson, Yacub, and Cheung for their interest in our work. In FINHYST, ‘Antibiotic prophylaxis for hysterectomy, a prospective cohort study: cefuroxime, metronidazole or both?’, our main result regarding antibiotic prophylaxis was that treatment with metronidazole in combination with cefuroxime was useless. Although anaerobes are involved at the surgical site, cefuroxime, which is secondgeneration cephalosporine is also effective against some anaerobic species. The pathogenesis of anaerobic infections involves (surgical) trauma and hypoxia, yet in order to initiate infection it seems that anaerobes require the presence of other bacteria.1 Therefore, as a prophylaxis against infections arising from the polymicrobial vaginal florae, cefuroxime
1576
seems sufficient. We must emphasise that metronidazole, or other antibiotics particularly targeted against anaerobes, do have an important place in the treatment of pelvic infections, but as a routine prophylactic agent, metronidazole seems to be a waste of money. The physiological warming balance, normally maintained by muscle work and tonus, is impaired during relaxation. Regional and general anaesthesia also cause periferic vasodilatation, resulting in redistribution that enhances hypothermia during surgery. Perioperative warming more than halves surgical-site infections.2,3 The use of forced-air blankets in Finland is very common, and is almost routine, but regarding our FINHYST study, information of coverage is lacking. The surgical site, however, must always be exposed. To our knowledge, the role of skin preps in temperature control has not been greatly discussed. Although the effect of such local wound-site cooling would appear to be temporary, and soon to be reversed, we find your results interesting. The optimal antibiotic prophylaxis tissue level should be reached by the time of contamination, i.e. when the bacteria gain access to the tissues.4 A vasoconstrictive effect on the skin might theoretically affect the tissue levels of the prophylactic antibiotics. As skin preps are essential, the beneficial effect of preoperative warming of the surgical site could more often be kept in mind.2 & References 1 McDonald PJ, O’Loughlin JA. Prophylactic antibiotics and prevention of surgical sepsis. Baillieres Clin Obstet Gynaecol 1993;7:219–36. 2 Melling AC, Ali B, Scott E, Leaper D. Effects of preoperative warming on incidence of wound infection after clean surgery: a randomised controlled trial. Lancet 2001;358:876–80. 3 Wong PF, Kumar S, Bohra A, Whetter D, Leaper DJ. Randomized clinical trial of perioperative systemic warming in major elective abdominal surgery. Br J Surg 2007; 94:421–6. 4 Classen D, Evans S, Pestotnik S, Horn S, Menlove R, Burke J. The timing of prophylactic administration of antibiotics and the risk of surgical wound infection. N Engl J Med 1992;326:281–6.
T Brummera & P H€arkkib a
Department of Gynaecology and Obstetrics, Porvoo Hospital, Porvoo, Finland b Department of Gynaecology and Obstetrics, Helsinki University Central Hospital, Helsinki, Finland Accepted 11 December 2013. DOI: 10.1111/1471-0528.12645
Effect of ethnicity on live birth rates after in vitro fertilisation or intracytoplasmic sperm injection treatment: possible explanations and further observations
Sir, Lower success rates of in vitro fertilisation (IVF) in South East Asian countries than Western countries in informal studies and surveys1 has always been considered a reflection of variations in methodology and expertise. Clearly, the recent article by Jayaprakasan et al.2 regarding the effects of ethnicity on the success rates of IVF and intracytoplasmic sperm injection (ICSI) in the UK would suggest other contributing factors. Jayaprakasan et al.2 have suggested some possible causes but full evaluation of these requires further extensive studies. We have developed a method of investigating the influence of ethnic group on prevalence, co-morbidity and other factors in a variety of conditions using completely anonymous hospital admissions data from multiple hospitals in Birmingham and Manchester, UK, using the ICD-10 and OPCS coding.3,4 According to this data set consisting of 522 223 female patients aged 18 and over, there were 44 758 (8.4%) patients from the South Asian community. From the overall female population, 8653 patients were coded for infertility, of which 1156 patients (13.4%) were of South Asian ethnicity, which is considerably higher than the proportion of the background South Asian female population. Of the 1479 patients coded for IVF procedures, the percentage of South Asian patients increased to 15.4% (233).
ª 2014 Royal College of Obstetricians and Gynaecologists
With regards to the use of rescue analgesia, the details can be found in Table S4 of the supporting information for the original article. One hundred and ninety-eight women (82%) in the diamorphine group, compared with 195 women (81%) in the pethidine group, received Entonox as rescue analgesia post-randomisation (P = 0.98). Fifty-nine (24%) in the diamorphine group and 42 (18%) in the pethidine group received epidurals post-randomisation (P = 0.07). The fact that over 80% of women in either group needed Entonox to supplement analgesia confirmed our conclusion that both analgesics gave modest pain relief. Furthermore, more than 84% of women from both groups reported verbally moderate to severe pain intensity over the first 3 hours of analgesia. Finally, we were asked to comment on the use of a 1-cm difference in visual analogue score (VAS) as the basis for the sample size calculation, and its subsequent labelling as a modest effect size. A detailed description of the rationale for choosing a 1-cm difference is provided in the published protocol for the study.2 The primary aim of our trial was to repeat what we suspected was an underpowered trial, which concluded that diamorphine was a better analgesic with reduced side effects when compared with pethidine.3 We have also explained in the discussion section of our paper the rationale for labelling a 1-cm difference in VAS as a modest difference.1 We believe it is difficult to describe the difference any other way, when the majority of women receiving either diamorphine or pethidine described their pain as being moderate to severe in intensity. As noted above, the following additional Supporting Information may be found in the online version of our article: Table S1. Baseline characteristics – outcome variables. Table S2. Maternal and neonatal outcomes. Table S3. Secondary outcome measures – Maternal pain variables. Table S4. Secondary outcome measures – Other maternal variables.
Table S5. Secondary outcome measures – Neonatal variables. Table S6. Mode of delivery. Appendix S1. IDvIP Trial: Data Collection Sheet. & References 1 Wee MYK, Tuckey JP, Thomas PW, Burnard S. A comparison of intramuscular diamorphine and intramuscular pethidine for labour analgesia: a two centre randomised blinded controlled trial. BJOG 2014;121:447–56. 2 Wee MYK, Tuckey JP, Thomas P, Burnard S. A two-centre randomised double-blind controlled trial comparing intramuscular diamorphine and intramuscular pethidine for labour analgesia. BMC Pregnancy Childbirth 2011;11:51. [www.biomedcentral.com/14712393/11/51]. Accessed 2 July 2014. 3 Fairlie FM, Marshall L, Walker JJ, Elbourne D. Intramuscular opioids for maternal pain relief in labour: a randomised controlled trial comparing pethidine with diamorphine. Br J Obstet Gynaecol 1999;106:1181–7.
MYK Wee,a JP Tuckey,b PW Thomasc & S Burnardb a
Poole Hospital NHS Foundation Trust, Poole, UK bRoyal United Hospital, Bath, UK c Clinical Research Unit,School of Health and SocialCare, Bournemouth University, Bournemouth, UK Accepted 11 June 2014. DOI: 10.1111/1471-0528.12986
There must be more to surgical wound infection prevention than antibiotic prophylaxis alone
Sir, We read with interest the article by Brummer et al.1 regarding their investigations into establishing an optimum antibiotic prophylaxis for hysterectomy. We share the interest that the FINHYST study has in trying to establish a methodology for reducing postoperative infectious morbidity. The benefit of antibiotic prophylaxis for hysterectomy was first demonstrated three decades ago.2 And, broadly speaking, antibiotic prophylaxis reduces the incidence of postoperative infection by half. But despite giving antibiotics – and
ª 2014 Royal College of Obstetricians and Gynaecologists
using appropriate antiseptic skin preparation – postoperative infection still occurs. This carries substantial cost implications and much patient dissatisfaction. As antibiotic prophylaxis has failed to abolish postoperative infections, one has to wonder whether other strategies need to be established. Peri-operative hypothermia is known to be a potent risk factor for developing wound infections,3 as well as being a risk factor for increased bleeding. Conversely, keeping patients warm during the peri-operative period reduces the risk of infections.4 Peri-operative hypothermia is easily preventable with the use of patient warming devices, which are widely available and relatively inexpensive. As well as maintaining normothermia, it makes sense to avoid hypothermia at the site of surgical incision. Hypothermia at the site of surgical incision can readily occur with some skin preparation agents. Because of the latent heat of vaporisation, ethanol-based skin prep causes a marked hypothermia at the site where it is applied. We measured the skin temperature of the ventral surface of the forearm of five volunteers in an operating theatre. The average skin temperature was 35.5°C. Alcohol-based skin prep (comprising 96% denatured ethanol) was applied and allowed to dry. The skin temperature was re-measured and on average was 27°C. The skin temperature remained at an average of 27°C 5 min later, and at 10 minutes no subject had a skin temperature above 30°C. For many years the management of breast cancer was confined to operative procedures, with depressingly poor results. Adjuvant treatments of radiotherapy, chemotherapy and anti-estrogen agents were introduced with superb results. Likewise, we feel the synergistic effect of adjuvant measures such as patient warming and avoiding inadvertent hypothermia at the site of surgical incision coupled with prophylactic antibiotics is what may well make
1575
BJOG Exchange
postoperative surgical infection a much rarer thing than it currently is. Certainly it is an avenue to explore. & References 1 Brummer T, Heikkinen A, Jalkanen J, Fraser J, M€ akinen J, Tom as E, et al. Antibiotic prophylaxis for hysterectomy, a prospective cohort study: cefuroxime, metronidazole, or both? BJOG 2013;120:1269–1276. 2 Cartwright P, Pittaway D, Jones H, Entman S. The use of prophylactic antibiotics in obstetrics and gynecology. A review. Obstet Gynecol Surv 1984;39:537–554. 3 Seamon MJ, Wobb J, Gaughan JP, Kulp H, Kamel I, Dempsey DT. The effects of intraoperative hypothermia on surgical site infection: an analysis of 524 trauma laparotomies. Ann Surg 2012;255:789–795. 4 Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization Study of Wound Infection and Temperature Group. N Engl J Med 1996;334:1209–1215.
MJ Dickson,a R Yakubb & K Cheungb a
Wayside, Cheshire, UK bRoyal Oldham Hospital, Oldham, Lancashire, UK
Accepted 24 September 2013. DOI: 10.1111/1471-0528.12644
Authors’ reply Sir, We thank Drs Dickson, Yacub, and Cheung for their interest in our work. In FINHYST, ‘Antibiotic prophylaxis for hysterectomy, a prospective cohort study: cefuroxime, metronidazole or both?’, our main result regarding antibiotic prophylaxis was that treatment with metronidazole in combination with cefuroxime was useless. Although anaerobes are involved at the surgical site, cefuroxime, which is secondgeneration cephalosporine is also effective against some anaerobic species. The pathogenesis of anaerobic infections involves (surgical) trauma and hypoxia, yet in order to initiate infection it seems that anaerobes require the presence of other bacteria.1 Therefore, as a prophylaxis against infections arising from the polymicrobial vaginal florae, cefuroxime
1576
seems sufficient. We must emphasise that metronidazole, or other antibiotics particularly targeted against anaerobes, do have an important place in the treatment of pelvic infections, but as a routine prophylactic agent, metronidazole seems to be a waste of money. The physiological warming balance, normally maintained by muscle work and tonus, is impaired during relaxation. Regional and general anaesthesia also cause periferic vasodilatation, resulting in redistribution that enhances hypothermia during surgery. Perioperative warming more than halves surgical-site infections.2,3 The use of forced-air blankets in Finland is very common, and is almost routine, but regarding our FINHYST study, information of coverage is lacking. The surgical site, however, must always be exposed. To our knowledge, the role of skin preps in temperature control has not been greatly discussed. Although the effect of such local wound-site cooling would appear to be temporary, and soon to be reversed, we find your results interesting. The optimal antibiotic prophylaxis tissue level should be reached by the time of contamination, i.e. when the bacteria gain access to the tissues.4 A vasoconstrictive effect on the skin might theoretically affect the tissue levels of the prophylactic antibiotics. As skin preps are essential, the beneficial effect of preoperative warming of the surgical site could more often be kept in mind.2 & References 1 McDonald PJ, O’Loughlin JA. Prophylactic antibiotics and prevention of surgical sepsis. Baillieres Clin Obstet Gynaecol 1993;7:219–36. 2 Melling AC, Ali B, Scott E, Leaper D. Effects of preoperative warming on incidence of wound infection after clean surgery: a randomised controlled trial. Lancet 2001;358:876–80. 3 Wong PF, Kumar S, Bohra A, Whetter D, Leaper DJ. Randomized clinical trial of perioperative systemic warming in major elective abdominal surgery. Br J Surg 2007; 94:421–6. 4 Classen D, Evans S, Pestotnik S, Horn S, Menlove R, Burke J. The timing of prophylactic administration of antibiotics and the risk of surgical wound infection. N Engl J Med 1992;326:281–6.
T Brummera & P H€arkkib a
Department of Gynaecology and Obstetrics, Porvoo Hospital, Porvoo, Finland b Department of Gynaecology and Obstetrics, Helsinki University Central Hospital, Helsinki, Finland Accepted 11 December 2013. DOI: 10.1111/1471-0528.12645
Effect of ethnicity on live birth rates after in vitro fertilisation or intracytoplasmic sperm injection treatment: possible explanations and further observations
Sir, Lower success rates of in vitro fertilisation (IVF) in South East Asian countries than Western countries in informal studies and surveys1 has always been considered a reflection of variations in methodology and expertise. Clearly, the recent article by Jayaprakasan et al.2 regarding the effects of ethnicity on the success rates of IVF and intracytoplasmic sperm injection (ICSI) in the UK would suggest other contributing factors. Jayaprakasan et al.2 have suggested some possible causes but full evaluation of these requires further extensive studies. We have developed a method of investigating the influence of ethnic group on prevalence, co-morbidity and other factors in a variety of conditions using completely anonymous hospital admissions data from multiple hospitals in Birmingham and Manchester, UK, using the ICD-10 and OPCS coding.3,4 According to this data set consisting of 522 223 female patients aged 18 and over, there were 44 758 (8.4%) patients from the South Asian community. From the overall female population, 8653 patients were coded for infertility, of which 1156 patients (13.4%) were of South Asian ethnicity, which is considerably higher than the proportion of the background South Asian female population. Of the 1479 patients coded for IVF procedures, the percentage of South Asian patients increased to 15.4% (233).
ª 2014 Royal College of Obstetricians and Gynaecologists
