D.G. Bogod

Pre-oxygenation and apnoea in pregnancy : changes during labour and with obstetric morbidity in a computational simulation

Using the Nottingham Physiology Simulator, we investigated the effects on pre‐oxygenation and apnoea during rapid sequence induction of labour, obesity, sepsis, pre‐eclampsia, maternal haemorrhage and multiple pregnancy in term pregnancy. Pre‐oxygenation with 100% oxygen was followed by simulated rapid sequence induction when end‐tidal nitrogen tension was less than 1 kPa, and apnoea. Labour, morbid obesity and sepsis accelerated pre‐oxygenation and de‐oxygenation during apnoea. Fastest pre‐oxygenation was in labour, with 95% of the maximum change in expired oxygen tension occurring in 47 s, compared to 97 s in a standard pregnant subject. The labouring subject with a body mass index of 50 kg.m−2 demonstrated the fastest desaturation, the time taken to fall to an arterial saturation < 90% being 98 s, compared to 292 s in a standard pregnant subject. Pre‐eclampsia prolonged pre‐oxygenation and tolerance to apnoea. Maternal haemorrhage and multiple pregnancy had minor effects. Our results inform the risk‐benefit comparison of the anaesthetic options for Caesarean section.

The sting in the tail: antiseptics and the neuraxis revisited

In 2001, Angelique Sutcliffe developed a progressive and debilitating adhesive arachnoiditis after apparently uneventful spinal anaesthesia for elective caesarean section, for which only hyperbaric bupivacaine 0.5% was administered. The path of her deterioration was steep and inexorable. Within a few days she had severe back pain, with urinary retention following shortly afterwards. Two weeks after delivery, she had signs of raised intracranial pressure, necessitating the insertion of a ventriculoperitoneal shunt to treat obstructive hydrocephalus. She developed worsening and ascending sensory and motor neuropathy in her legs over the following weeks and, having undergone further surgery to treat recurrent raised intracranial pressure, became progressively paraplegic with limited use of her arms. Her magnetic resonance imaging scans show a spinal cord severely damaged as a result of multiple dense adhesions. Infection was ruled out early on as a cause for Ms Sutcliffes neuropathology, and there was no evidence to support the view that a syringe swap error had led to administration of the wrong drug. After the lengthy delay that often accompanies civil claims, a High Court judge in 2007 had to decide whether she had been negligently treated and, if so, to award monetary compensation. On expert advice, he concluded that, on the balance of probabilities, the injectate had become contaminated with ‘a measurable quantity’ – defined as 0.1 ml or more – of the chlorhexidine 0.5% in alcohol 70% used for skin preparation [1]. I robustly argued against this conclusion in an article in Anaesthesia News, on the grounds that the anaesthetist and operating department practitioner had been quite meticulous in minimising the risk of such chlorhexidine spillage on to the sterile field and that there was absolutely no evidence that such contamination had taken place [2]. Events since 2007 have, however, led me to conclude that the Honourable Mr Justice Irwin got it right, and I got it wrong. Specifically, in June 2010 in Sydney, Australia, Grace Wang, in labour in her first pregnancy, requested epidural pain relief. Chlorhexidine 0.5% in alcohol had been poured into one pot on the sterile field and saline into the other, and the anaesthetist chose the wrong container from which to draw up 8 ml of fluid to flush down the Tuohy needle into the epidural space (personal communication leads me to understand that – contrary to a widely stated view – the chlorhexidine was not colourless, but that the first epidural attempt had led to a bloody tap, the fluid from which had turned the contents of the saline pot pink, thus masking the usual colour difference) [3]. The contrast between these two stories is of course that, in the latter case, we know for certain that chlorhexidine had been administered into the neuraxis, but otherwise they are strikingly similar. Grace Wangs clinical deterioration was, to all intents and purposes, identical to Angelique Sutcliffes, including the time course, the progressive and relentless neurological deterioration, the need for emergency ventricular drainage and the development of an ascending motor and sensory neuropathy leading to paraplegia and upper limb involvement. This has inevitably led me to re-examine my response to the Sutcliffe case and toconclude that chlorhexidine in alcohol was the probable causative factor. These cases are not isolated examples. Through my own medicolegal practice, I am aware of two further obstetric cases. In the first, an epidural was sited in labour, the patient complaining of severe headache during the procedure. There is no record of how the skin was prepared. The epidural was later topped up for caesarean section, theonly drugs used for labour ordelivery being bupivacaine, levobupivacaine and fentanyl. In the

Paternalism and consent: has the law finally caught up with the profession?

pdf (accessed 26/06/2015). 15. Ministry of Justice. Criminal Justice and Courts Act 2015. Circular 2015/01. Para 69, p.16. https://www.gov.uk/go vernment/uploads/system/. . ./cjc-actcircular.pdf (accessed 26/06/2015). 16. Department of Health. New offences of ill-treatment or willful neglect. Government response to consultation. June 2014. https://www.gov.uk/gover nment/consultations/ill-treatment-orwilful-neglect-in-health-and-social-care (accessed 26/06/2015). 17. Ministry of Justice. Criminal Justice and Courts Act 2015. Explanatory notes. http://www.legislation.gov.uk/ukpga/ 2015/2/notes/division/2 (accessed 26/06/2015). 18. Social Action, Responsibility and Heroism Act 2015. http://www.legislation. gov.uk/ukpga/2015/3/contents/enacted (accessed 26/06/2015). 19. General Medical Council. Openness and honesty when things go wrong: the professional duty of candour, June 2015. http://www.gmc-uk.org/DoC_g uidance_englsih.pdf_61618688.pdf (accessed 06/07/2015). 20. Devlin M. The new criminal sanctions of willful neglect or ill-treatment. 9th April 2015. http://www.themdu.com/ guidance-and-advice/latest-updates-an d-advice/the-new-criminal-sanctions-of -wilful-neglect-or-ill-treatment (access ed 26/06/2015). 21. McDowell SE, Ferner RE. Medical manslaughter. British Medical Journal 2013; 347: f609. 22. Nash L, Daly M, Johnson M, et al. Psychological morbidity in Australian doctors who have and have not experienced a medico-legal matter: cross-sectional survey. Australia and New Zealand Journal of Psychiatry 2007; 41: 917–25. 23. Bourne T, Wynants L, Peters M, et al. The impact of complaints procedures on the welfare, health and clinical practise of 7926 doctors in the UK: a cross-sectional survey. BMJ Open 2015; 5: e006687. 24. Ennis M, Vincent C. The effects of medical accidents and litigation on doctors and patients. Law and Policy 1994; 16: 97–121. 25. General Medical Council. Good Medical Practice, 2013. http://www.gmc-uk.or g/static/documents/content/Good_m edical_practice_-_English_0914.pdf (accessed 26/06/2015).

The postpartum stomach—when is it safe?

The protection of the lungs from soiling by acid stomach contents is a basic tenet of anaesthetic practice, and it has long been accepted that the pregnant woman undergoing general anaesthesia is at particular risk from such an occurrence. The near universal use in the UK of H,-receptor antagonists, antacids and rapid-sequence induction with cricoid pressure is the culmination of a sequence of precautionary measures which began after Mendelson’s classic paper [ 11 described the hazards of pulmonary aspiration in pregnancy; widespread acceptance of these precautions may well be a factor in the gradual reduction in maternal mortality due to acid aspiration culminating in the latest encouraging figures [2]. The apparent success of these measures has led, not surprisingly, to their being adopted for routine use in the postpartum period, so that women undergoing surgical procedures after delivery are regularly submitted to the full panoply of precautions. What are the risks and benefits of such an approach? It may be thought, and is often argued, that using the H,-blocker/antacid/rapid-sequence approach can be of no detriment to the patient. However, in the real world every drug has adverse effects, and there have been reports of life-threatening anaphylactoid reactions to ranitidine in pregnant women [3,4]. Furthermore, a rapid, thiopentone-suxamethonium induction is likely to cause significant cardiovascular instability and, because of its hurried nature, may contribute to the high incidence of failed tracheal intubation in obstetric anaesthesia. It may be that anti-aspiration prophylaxis is not as benign as is often imagined, in which case we should only be using it if a real benefit can be shown. It therefore behoves us to look more closely at the factors which might be expected to put the postpartum patient at particular risk of acid aspiration: gastric emptying, pH and volume of stomach contents and gastrooesophageal reflux. Considerable confusion exists about the true effect of pregnancy on gastric emptying. In fact, once the effects of labour [5] and opioids [6] have been eliminated, there appears to be remarkably little evidence of delay as a result of pregnancy per se. Using paracetamol absorption, MacFie et al. could show no significant delay in gastric emptying in first, second or third trimester patients when compared to nonpregnant controls [A. These findings are confirmed by Whitehead and her colleagues who continued their study into the period after delivery [8]. Gin et al. demonstrated rapid gastric emptying one day postpartum, which was unchanged when measurements were repeated on the 3rd day and 6 weeks later [9]. Applied potential tomography (APT) is a recently developed technique which overcomes the criticism that the paracetamol absorption method may be flawed because of pharmacokinetic changes in pregnancy. Using APT, Sandhar and colleagues have shown that the mean time to 50% emptying is the same in the third trimester and 2-3 days postpartum as in the same group of women 6 weeks after delivery [lo]. Do the pH or volume of gastric contents in the postpartum woman differ from those in nonpregnant controls? Raised gastrin levels are responsible for hypersecretion of acid during pregnancy and these begin to fall within 30 min of delivery [ 1 11. As far back as 1976, Blouw et al. demonstrated that there was no significant difference in either of these parameters when a group of postpartum patients (mean time from delivery 19.5 h) was compared with controls [12]. Lam and colleagues have confirmed these findings in women ranging from 12 to 120 h after delivery, and have also shown that pH and volume are unaffected by allowing intake of 150 ml of water 2-3 h pre-operatively [ 131. James was unable to show any significant difference in the incidence of pH < 2.5, pH 1.4 or > 25 ml in gastric aspirates of women 1-8 h postpartum when compared to controls [14]. These studies are also unanimous on another point: well over 50% of the patients involved, whether postpartum or controls, had gastric pH < 2.5 and many of these also had volumes greater than 0.4 ml.kg-’. These criteria are widely regarded as the point beyond which aspiration leads to a high risk of Mendelson’s syndrome, although on very slim evidence [15]; it seems that a large proportion of our patients, pregnant or not, have dangerous gastric contents, and yet the incidence of acid aspiration in normal practice is vanishingly small. It is possible that we have been over-conservative in our assumptions about what is dangerous; a study using primates has suggested that a volume greater than 80 ml with a pH of less than 1 .O is needed before serious pulmonary damage occurs [16]. The other possibility is that our patients are protected by the gastro-oesophageal junction, which keeps harmful stomach contents in their proper place; any estimate of the risk of acid aspiration in the postpartum period should also consider this factor. Gastro-oeophageal reflux is reported by 80% of women at term [17], and an increased incidence of reflux at term, even in the absence of symptoms, can be demonstrated by monitoring pH in the lower oesophagus [18]. This is probably due partly to the mechanical effect of the gravid uterus increasing gastric pressure, but also to the relaxant effect of progesterone on the smooth muscle of the lower oesophageal sphincter [ 191. Plasma progesterone concentration decreases within 24 h of delivery to levels found in the luteal phase of the menstrual cycle [lo], and this, combined with relief of the external pressure on the stomach, might be expected to have a salutary effect on the incidence of reflux. Vanner and Goodman have studied this in a group of conscious women at term and 24-80 h postpartum [21]. Using lower oesophageal pH monitoring, they looked at the frequency and duration of reflux in four positions, including lithotomy, and used provocation manoeuvres if spontaneous reflux was not found. Despite their best endeavours, only five out of the 25 postpartum women refluxed, compared to 17 out of 25 before delivery. This figure of 20% is actually lower than the incidence found in normal, nonpregnant control subjects [22]. Where does this leave the obstetric anaesthetist presented with a woman for postpartum sterilisation, perineal suturing, or evacuation of retained products of conception? With labour completed there seems little doubt that, once the pernicious effects of intrapartum opioid drugs have disappeared, rate of emptying, pH,

A long and dangerous journey: maternal mortality in Africa

Looking back over the last century from our vantage point at the turn of the Millennium, the reduction in maternal mortality in the developed world must surely be one of the great triumphs of medicine. Not that this advance was realised quickly; whether a mother in the UK gave birth in 1900 or 1941, she still ran a one in 200 chance of dying [1]. It was only after the Second World War, with the development of antibiotics and blood transfusion, that the risks of childbirth started to diminish; by the early 1950s the rate had dramatically declined to one in 1500 [2]. The situation has continued to improve, and between 1994 and 1996 the maternal mortality rate in the UK was 12.2 per 100 000 maternities, making a British woman’s risk of dying as a result of a given pregnancy at around one in 10 000 [3]. The contribution of anaesthetists to this spectacular public health success is a notable achievement, with the number of deaths directly due to anaesthesia steadily decreasing until the last Triennial report, which identified only a single death in this category [4]. Ironically, it is the speed of progress in the developed world that makes the global inequalities in this area particularly stark. In this edition of Anaesthesia, Fenton affords us a glimpse of his adopted country of Malawi, where he has striven tirelessly to provide anaesthetic services for 13 years, an effort which recently led the Association of Anaesthetists of Great Britain and Ireland to award him a Pask Certificate of Honour. Fenton reports that the estimated maternal mortality rate in Malawi is between 415 and 620 deaths per 100 000 maternities, some 50 times that in the UK. One in 20 women who are judged to need a transfusion of two units of blood after Caesarean section die, and this increases to one in five if three units are needed [5]. The rest of sub-Saharan Africa – with the notable exceptions of South Africa, Botswana, Namibia and Gabon – is in a similar situation. The region accounts for 23 of the 34 countries estimated as being furthest away from the four international development goals of the World Health Organisation (WHO), one of which relates to maternal mortality. Inevitably, it is often the poorest countries with the highest death rates which are unable to provide accurate statistics, and this may lead to an underestimate of maternal mortality in some areas. When the data do emerge, they dwarf even the figures provided by Fenton; reliable sources in Ethiopia report an overall maternal mortality rate of 1400 per 100 000 live births, rising as high as 2.6% for all live and stillbirths in Jimma Hospital in the SouthWestern region of the country (F. Surur, personal communication). This sorry situation is certainly not confined to Africa. Current WHO estimates suggest that women in Asia have a one in 65 lifetime risk of dying as a result of pregnancy or childbirth and that the equivalent figure for Latin America and the Caribbean is one in 130 [6]. These contrast markedly with the overall risk of one in 1800 for women in developed countries. Globally, an estimated 585 000 women die each year as a result of pregnancy, with 99% of these deaths occurring in the developing world [7]. But it is in Africa, more than anywhere else, that maternal survival is at its most precarious, because the high mortality rate is compounded by high fertility. In rural areas it is not uncommon for women to have eight children (and many more pregnancies); this means that the lifetime risk of dying from pregnancy-related causes for some African women may be as high as one in 16, over 100 times greater than that in Europe and North America [6]. Of all the health statistics monitored by the WHO, maternal mortality shows by far the largest discrepancy between the developed and developing worlds. While the high infant death rate in the developing world is popularly regarded as one of its greatest tragedies, the seven-fold disparity in this measure [8] is far outweighed by the 18-times greater maternal death rate [6], not so much a health gap as a gaping chasm. Small wonder that African mothers about to give birth sometimes bid their older children farewell, saying: ‘I am going to the sea to fetch a new baby but the journey is long and dangerous’ [9]. With mortality, of course, comes morbidity, and for every woman in the developing world who dies as a direct result of pregnancy, 100 more suffer from severe complications, one-third of which will result in long-term, and often debilitating, effects. Of these, the most pernicious are recto-vaginal and vesicovaginal fistulae. It has been estimated that 80 000 women per year develop fistulae, almost invariably resulting from prolonged, obstructed labour, and that between 500 000 and one million women currently suffer from this problem; many become social outcasts, turned out of their homes and rejected by their husbands and families [10]. Obstructed labour can also lead to damage to the lumbosacral plexus, causing crippling loss of sensory and motor function in the lower limbs [11]. Death and disability related to maternal causes account for 18.5% of the burden of disease among women of reproductive age in developing countries [12]. The consequences of this cataclysm do not stop with the mother alone. The death or disability of a young woman in her prime and when she is at her most economically and socially productive has far-reaching implications. The baby is very likely to die, as are any infants still breast-feeding and her other children, often too young to fend for themselves, will almost inevitably suffer impaired health and malnutrition. While the incidence of maternal death varies so widely around the world, the causative factors are much the same. Haemorrhage, pregnancyinduced hypertension and sepsis regularly appear among the top six causes of death in the Reports on Confidential Enquiries into Maternal Deaths in the Anaesthesia, 1999, 54, pages 1025–1027 ................................................................................................................................................................................................................................................

CONTINUOUS EPIDURAL INFUSION

The use of filters for epidural anaesthesia is a well established practice in the United Kingdom. The use of filters for drawing up agents for spinal anaesthesia is, howevcr, less widesprcad at prescnt. James et ul.‘ showed that the Millex filter reduced contamination from syringes which were refilled several times over a period of hours during obstetric epidural anaesthesia. The drawing up, under sterile conditions, of a ‘single shot’ dose of local anaesthetic agent is hardly comparable to this situation. Crawford? highlighted the dilemma about all sterile precautions for obstetric regional anaesthesia when he contended that, although the evidence that filter use is effective is inconclusive, a filter seems a relatively inexpensive and reasonable precaution. It is as yet unproven whether the use of filters reduces the incidence of meningitis after spinal anaesthesia and it would seem precipitate to consider their use to be mandatory. The use of filters, although protective against bacterial and particulate contamination, would not prevent chemical contamination of the cerebrospinal fluid.

Flow characteristics of Luer and non‐Luer spinal needles

We investigated the flow rates of 25‐G and 27‐G spinal needles, of 90‐mm and 120‐mm lengths, from Vygon, BD, B. Braun and Pajunk; the needles had either a Luer connector, or a Surety® or UniVia® non‐Luer connector. We used a bench‐top model of entering the spinal space, pressurised to 35 cmH2O to simulate cerebrospinal fluid pressure in the sitting position. We examined the time to first appearance of simulated cerebrospinal fluid in the needle hub, as well as the amount of fluid collected over 120 s after the needle was introduced. The mean (SD) times to first appearance of fluid in the needle hub of Luer spinal needles varied from 0.36 (0.22) s for the 25‐G 90‐mm BD to 3.14 (0.72) s for the 27‐G 120‐mm B. Braun, and in the non‐Luer spinal needles from 0.22 (0.17) s for the 25‐G 90‐mm B. Braun to 2.99 (0.71) s for the 27‐G 120‐mm Pajunk. There was a significant difference in the time to first appearance of fluid in the needle hub between Luer and non‐Luer needles of the same type for seven of 14 comparisons made, of which four showed slower appearance of fluid in the non‐Luer version. In some of these cases, the time to appearance of fluid was nearly twice as long with the non‐Luer counterpart. The mean (SD) weight of fluid collected in 120 s using the Luer spinal needles varied from 0.21 (0.05) g for the 27‐G 120‐mm Pajunk to 1.21 (0.18) g for the 25‐G 90‐mm Vygon, and using the non‐Luer spinal needles from 0.25 (0.05) g for the 27‐G 120‐mm Pajunk to 1.55 (0.05) g for the 25‐G 90‐mm B. Braun. All of the needle types showed a greater weight of fluid collected using the non‐Luer compared with the Luer version, with six of the 14 needle types showing a significant difference. Significant variations in flow were also seen between the same needle type from different manufacturers. We conclude that changing from Luer to non‐Luer versions of spinal needles does not merely change the hub design and connection, but may introduce important differences in function.

The Editor as umpire: clinical trial registration and dispute resolution

It is often the lot of the Editor-in-Chief of a scientific journal to mediate in disputes between authors, researchers and clinicians. The best and most constructive disputes are those which seek to clarify issues for the benefit of the readership and, ultimately, their patients. However, not all disputes fall into this welcome category. A recent conflict which has greatly exercised members of the Editorial Boards of this and other journals carries some useful lessons for researchers, authors, editors and readers, and has led us to suggest some changes in practice which may reduce the risk of recurrence. Dr W-M. Ho and his team submitted a paper to this journal in early 2005 in which they tested the accuracy of a modified equation for predicting the mixed venous blood concentration of sevoflurane from inspired and expired concentrations by measuring the true mixed-venous concentration during cardiac surgery in 12 patients. Similar papers relating to isoflurane and desflurane were submitted to other specialist journals during the same period, and all were eventually accepted and ultimately published [1–3]. Following publication (in two cases) and acceptance (in one), all three editors received correspondence from another researcher in the same field who had, at one time, been a colleague of the lead author. These letters raised specific and serious concerns about technical and ethical aspects of the studies. At around the same time, all three editors received letters from the Institutional Review Board (IRB) of the hospital where the studies had been conducted. After some initial confusion, it transpired that a special investigations panel had been set up and that, following an enquiry lasting some weeks, the panel had found that, with respect to these three papers and three others, the lead author had (a) failed to obtain IRB approval for his study, (b) did not have written informed consent, and (c) was not able to produce full raw data and log books. This would, in normal circumstances, have led to the papers being withdrawn by publishing a formal notice in the respective journals and in relevant internet search engines. However, in this case extensive further enquiries were made by all three editors acting in concert. Space does not permit a full description of the steps that were taken, but we eventually concluded that, when they conducted these studies, the authors’ practices conformed to the prevailing ethical standards in their institution at that time. Specifically, we found that, at the time of the events in question, ethics approval was considered to be granted once a study had been approved and funded by the hospital’s Research and Education Committee and countersigned by the Hospital Superintendent. The need for informed consent for the type of study in question, which only involved the extraction of small blood samples from existing lines while under anaesthesia, appears either not to have existed at all, or to have been widely ignored. The paper which had been accepted for publication by Acta Anaesthesiologica Scandinavica, and which had been held back during the investigation, was duly published [3]. It might be thought that this would mark the end of what was a difficult and time-consuming process involving all three editors. However, journal editors often demand higher ethical standards than those required by hospitals and universities. Our instructions to authors make it very clear that Research Ethics Committee (IRB) approval is required and that ‘full prospective written informed consent should be obtained from all subjects of clinical trials...’ [4]. The paper as submitted to Anaesthesia appeared to conform to this directive, the authors stating: ‘Following ethics committee approval, 13 ASA physical status II or III adult patients undergoing cardiac surgery with normal pulmonary function and who gave written informed consent were enrolled in the study’. During our investigations, however, the lead author admitted that: ‘Written consent for anaesthesia and surgery was considered sufficient at that time for this sort of study, although the rules had since changed’. It seemed from this that, whereas I had believed that the trial subjects had given specific written consent to participate in the study, in fact this was not true. Following discussion with the Editorial Board and consideration by the Committee on Publication Ethics, a national forum for scientific journal editors, I decided that this matter, while serious, did not warrant withdrawing the paper, and this editorial and a letter to the lead author will, as far as the journal is concerned, draw a line under the matter. I have described a case where serious allegations with regard to an author were not upheld. All too often, though, research fraud and malpractice is so serious that it can undermine the integrity of journals and editors, and lead to the dissemination of false science. How can such problems be prevented in the future? The short answer is that they cannot. The timehonoured method of disseminating experimental findings – submission, peer review, publication and critique – is entirely dependent upon a high level of mutual respect and trust between author and editor. With very few exceptions, editors do not have the time or money to examine raw data and original documentation. Fraudulent researchers are sometimes brought to book by dint of a full, rigorous investigation, but the effort involved is daunting even to the most well-respected and heavily staffed journals [5]. Most scientific fraud is detected through local Anaesthesia, 2006, 61, pages 1133–1137 .....................................................................................................................................................................................................................

Strength of commonly used spinal needles: the ability to deform and resist deformation

We investigated the strength of commonly used spinal needles in relation to the amount of deformation, and registered forces during standardised testing. We investigated differences between manufacturers for the same length and gauge of Luer and non‐Luer needles, and examined the effect of the internal stylet in terms of needle strength. A specialised rig was designed to perform the testing in both the horizontal and axial plane, reflecting common industrial tests and clinical use. Needles from four commonly used manufacturers were used (Vygon, Becton Dickinson, B Braun, and Pajunk). Needles of 25 G and 27 G were tested in 90‐mm and 120‐mm lengths. We found significant differences in terms of the size of final deformation and ‘toughness’/resistance to deformation between needles of different brands. There were also significant differences between horizontal tests conducted as an industry standard and our own axial test. This may have bearing on clinical use in terms of the incidence of bending and breakage. The presence of the internal stylet resulted in significantly greater toughness in many needles, but had little effect on the degree of deformation. Comparison of Luer and non‐Luer needles of the same brand and size showed few significant differences in strength. This result is reassuring, given the imminent change from Luer to non‐Luer needles that is to occur in the UK.