Does Anaesthesia Drive You Mad?
Blaming The Anaesthetic For Post-Operative Cognitive Dysfunction
Author: Dr Karen Stuart-Smith, Consultant Anaesthetist, Glan Clwyd Hospital, Denbighshire, Wales

Antiplatelet Drugs And Perioperative Bleeding: Doesn’t Anybody Care?
Author: Dr Karen Stuart-Smith, Consultant Anaesthetist, Glan Clwyd Hospital, Denbighshire, Wales

Delivering Anaesthesia To Developing Countries
Author: Rebecca Griffiths, Diamedica Ltd

The High Risk Obstetric Patient – Anaesthetic Implications
Author: Dr. Mary Korula, Professor, Dept. of Anaesthesia, Christian Medical College, Vellore Tamil Nadu, India

Association of Anaesthetists of Great Britain & Ireland
Royal Dublin Society, Ireland 12-14 September 2007

Does Anaesthesia Drive You Mad?
Blaming The Anaesthetic For Post-Operative Cognitive Dysfunction
Author: Dr Karen Stuart-Smith, Consultant Anaesthetist, Glan Clwyd Hospital, Denbighshire, Wales

No doubt many of you will have read a short article in a previous issue of this magazine which described a piece of research claiming that isoflurane use was linked with the onset of dementia¹. I didn’t think much of the article myself, but when reading through the whole APN issue prior to printing, I though it was of minor importance and didn’t object to its inclusion. However I have since been the recipient in my own department of a round robin letter containing the abstract from the original article, at least twice, with a cautionary note that this was ‘something to think about’, so my lack of due diligence as an editor came back to haunt me! I strongly suspect that similar round robin letters were distributed in anaesthetic consultant pigeonholes up and down the country. If you did this, shame on you, and I’m going to use this article to explain why.

The problem with the way we teach medicine is that we choose people with good A-levels and then make them spend 5 years memorising things. In other words, we take people who have a tendency to believe everything they read in books and then spend their whole university and postgraduate career reinforcing this belief. As research is considered a rather lower class and irrelevant line of activity, the ability to treat reported research findings with both an open mind and a degree of scepticism is missing. Thus, when clinicians read original research journals, they believe everything they read in there in the same way that they believe everything that is written in books, and there is a real danger that this has happened with the article mentioned above, with the potential for unnecessary alarm. What really annoys me is that the paper in question does not even concern research done in patients, but on cells in culture. Further, I would be willing to bet that none of the round robin letter distributors understood a word of the abstract they were distributing. I’d also lay money that no-one has read the original paper, nor other papers from the same group, nor put the paper into the context of all the other literature on the subject, before shoving it in our pigeon holes as ‘something to think about’. This is dangerous and lazy thinking. Luckily, I have done all the necessary reading, and can reveal the fallacies inherent in the much-championed research.

Let us look at the paper itself¹. The premise of the paper revolves around a specific biological model for the onset of Alzheimer’s disease, so I will describe this model first.

Alzheimer’s disease (AD) is defined as an age-related neurodegenerative dementia. The most prominent clinical feature of this type of dementia is progressive memory loss, followed by gradual deterioration in global cognitive abilities, and premature death. Most cases are sporadic, suggesting environmental influences in the aetiology. A small number are familial and reflect specific gene mutations that have been helpful in understanding the pathogenesis of the disease². Pathologically AD is characterised by intracellular neurofibrillary tangles (composed of tau protein), and intracellular senile plaques (amyloid). These changes are most obvious in the hippocampus, which is involved in the processing and laying down of memory. There is also widespread neuronal loss, as well as loss of synaptic communication between the remaining neurons. This last feature correlates well with the degree of dementia.

Figure 1. Cartoon depicting the proteolytic processing of amyloid precursor protein (APP) via non-amyloidogenic (left) and amyloidogenic (right) cleavage. Non-amyloidogenic cleavage occurs when a-secretase acts to liberate sAPPa and C83, the latter being cleaved by g-secretase to generate p3. Amyloidogenic cleavage by b-secretase liberates sAPPb and the residual peptide is cleaved to produce C88 and Ab. Ab in turn can be degraded by enzymes including neprilysin, insulin degrading enzyme and endothelin cleaving enzyme (not shown). Figure 1 is taken from reference 3, with kind permission from Professor Chris Peers, University of Leeds and Blackwell Publishing

The senile plaques consist of a protein called beta amyloid (Aß). The abnormal accumulation of Aß is thought to be the cause of the clinical manifestations of AD. Aß is derived from a large transmembrane glycoprotein present in central neuronal cells called amyloid precursor protein (APP). APP is somewhat misnamed as it does have vital neurophsyiological functions – it is not simply sitting there waiting to be broken down into nasty beta amyloid³. Essentially there are two pathways for APP breakdown: amyloidogenic and non-amyloidogenic (figure 1). The non-amyloidogenic breakdown of APP by an a-secretase produces a number of peptide fragments which are largely unexplored, and so will not be discussed further. The amyloidogenic pathway for breakdown of APP is mediated via a ß-secretase enzyme, and then further enzymatic cleaves occurs via another enzyme, g-secretase, to yield Aß (figure 1). The g-secretase enzyme contains two important subunits, termed presenilin-1 and presenilin-2 (PS1 and PS2), which are necessary for the controlled breakdown of APP to Aß. Aß in normal physiological concentrations probably regulates synaptic activity, and blocking production of Aß (by inhibiting b- and g-secretases) results in neuronal cell death³. It is the excessive accumulation of Aß which results in the symptoms and signs of Alzheimer’s disease.

It used to be thought that the extracellular senile plaques, containing Ab, were the source of the clinically observed dementia. However, plaque accumulation correlates poorly with a degree of neurological dysfunction, and it is more likely that it is intracellular deposition of amyloid in the neuronal cells themselves that precipitates the cognitive dysfunction, and is probably a much earlier manifestation of the disease than plaque formation⁵. Abnormal accumulation of Ab inside central neurons causes apoptosis (death) of these cells⁶ (figure 2).

Figure 2. Synthesis, trafficking and retrieval of Ca2+ channels from the plasma membrane. Cartoon depicting the synthesis, trafficking and retrieval of Ca2+ channels from the plasma membrane under normoxia (upper picture). During sustained hypoxia, a rise of ROS from mitochondria triggers increased Ab‚ formation which has multiple effects (see text for full description) including direct neuroprotection, increased transcription of protective factors such as vascular endothelial growth factor (VEGF) via stabilization of HIF, and altered trafficking of Ca2+ channels so that more are present and active in the plasma membrane. Figure 3 is taken from reference 3, with kind permission from Professor Chris Peers, University of Leeds and Blackwell Publishing

There are several genetic mutations in the amyloid precursor protein itself, and in the presenilins, which predispose this protein to be broken down to Aß in abnormal quantities. These genetic mutations generally account for familial susceptibility to Alzheimer’s disease⁴. Sporadic AD, which accounts for the majority of cases, is thought to be the result of various environmental influences which result in neuronal oxidative stress and enhanced breakdown of APP to Ab4. The ‘environmental influences’ are still rather vague at present, but include the usual suspects such as diet (raised cholesterol) and excessive alcohol consumption (although modest red wine consumption appears to be protective, luckily). The most well documented type of oxidative stress which has been linked to Alzheimer’s disease is prolonged severe hypoxia, which appears to cause up-regulation of Ab production³ (figure 3).

What has this all got to do with anaesthesia driving you mad? The authors of the original offending article1 equate Alzheimer’s Disease with post-operative cognitive dysfunction (POCD) in several of their publications^7,8. Are they justified in this assumption? POCD is defined as a persistent impairment of neuropsychological function, including information processing and memory, in the immediate post-operative period⁹. By persistent is meant after any residual effect of sedation and anaesthesia has presumably worn off. A long-running multicentre study (the International Study of Post-Operative Cognitive Dysfunction, ISPOCD)¹⁰, has produced the following information. Approximately 25% of elderly patients (age > 60) exhibited signs of POCD 1 week after surgery, and 10% still showed signs of POCD 3 months later¹⁰. 1-2 years later, 1% of elderly patients fell into this category¹¹. Thus, POCD is a real phenomenon. But, before you reach for the vapouriser to switch it off, there are a few caveats. In early POCD, the risk factors are age, duration of anaesthesia (and also therefore duration of the operation and the stress response), little education, a second operation, postoperative infections and respiratory complications. At 1 year the risk factors are age, early POCD and infection. In other words, being an elderly patient having a big operation, a post-operative infection, repeat surgery, and a spell in ITU on a ventilator will cause post-operative cognitive dysfunction. POCD is multi-factorial and is not an isolated effect of anaesthesia. The stress response to the surgery is probably a far bigger factor. This is a classic case of the surgeons blaming the anaesthetic for a post-operative problem and we must stop agreeing with them!

Fig. (3). Scheme of intraneuronal pathogenesis of Ab42. Overproduction of Ab42 or aberrant folding of Ab42 induces ER stress, and transfer of Ab42 into the cytosol. Ab42 accumulating in the cytosol damages mitochondria interacting with ABAD, and induces apoptosis. Simutaneously, some of the accumulated Ab42 damages the synapse, or is transferred to the nucleus by AB-DIP inducing p53 mRNA overexpression and apoptosis. Reduction of cytosolic Ab42 levels may thus protect neurons from severe apoptosis in AD. Figure 2 is taken from reference 6, with kind permission from Bentham Science Publishers Ltd

What is the biochemical mechanism for POCD? This is completely unknown, and there is no scope (or evidence) to speculate here. For the obvious reason that you can’t simply take a brain sample from a living patient with POCD, there is no evidence one way or the other for a role for Ab, the offending amyloid in Alzheimer’s disease. With regard to a clinical link between Alzheimer’s disease and POCD, there is no evidence at all that these have similar mechanisms, and certainly no recent, well-conducted population studies to suggest a specific link between anaesthesia and subsequent development of POCD. The research papers quoted by the authors of the offending article¹ are 13 years old, small, retrospective studies of case notes, and do not control for any other factors^12,13. Furthermore, these papers showed that Alzheimer’s was as likely whether a general or a regional anaesthetic was used¹³, and also that cumulative exposure to general anaesthesia did not correlate with later development of Alzheimer’s disease¹². I would suggest that our offending authors did not read their references properly, but may have made some assumptions about the content of these references, based on their own theories regarding general anaesthetics and Alzheimer’s disease. If they are reading this and feel otherwise, they should feel free to respond.

What of the concept that isoflurane induces post-operative cognitive dysfunction and/or Alzheimer’s disease by promoting neuronal cell death? Let us look first at the potential for a specific role for isoflurane in POCD. We have already seen that the use of an anaesthetic of any description is the main or even the most likely cause of POCD. A study published this year (2007) compared the incidence of POCD with type of inhalational anaesthetic used in patients undergoing cardiac surgery¹⁴. Neuropsychological scores on the third and sixth post-operative days were significantly higher in patients who had isoflurane anaesthesia as compared to those who had sevoflurane and desflurane, so tough luck to all of you out there who put the offending article in your colleagues’ pigeon holes because you hate isoflurane. Only desflurane was associated with a significant rise in the cerebral injury marker S100 beta protein, and the relevance of this is unclear, as a) this was a small group of patients, and b) the correlation between S100 protein and POCD is not proven¹⁵. To illustrate this latter point, a previous study by the same group showed that that there was no difference in rates of POCD between cardiac patients anesthetised with isoflurane and those who received propofol, even though post-operative S100 levels were significantly elevated in the propofol (but not the isoflurane) group¹⁶. Neurocognitive dysfunction was minor in all affected patients in any case. There is therefore no evidence in the literature at all that isoflurane is specifically associated with POCD. In fact, isoflurane is protective against cerebral ischaemia¹⁷, and can actually improve outcome after a cerebral ischaemic event.

Let us now take a close look at the experiments performed by our offending authors. The studies were performed on cultured human neuroglioma cells (yes, you can buy these off a shelf, those who feel short of brain power). These cells were subjected to 6 hours of 2% isoflurane exposure in a 21% O2/5% CO2 mixture (balance was nitrogen). Two types of neuroglioma cells were used: ‘naïve’ or wild-type cells, which had not been altered in any way (except that they are a cultured cell line, not actual human brain tissue), and cells which had been altered to express human APP in large quantities. 2% isoflurane was chosen because previous studies by this group showed that 1% isoflurane had no effect on the neuroglioma cells-a point worth bearing in mind¹⁸. At any rate, subjecting the naïve cells to 2% isoflurane for 6 hours caused up-regulation of an apoptosis related protein called caspase-3, implying that higher concentrations of isoflurane can induce apoptosis even without altering APP metabolism. In the cells which contained artificially added APP, isoflurane enhanced the levels of b- and g- secretase, resulting in an accumulation of Ab inside the neuroglioma cell. This action of isoflurane was blocked by blocking the formation of caspase-3. The sequence of events is thought to be: direct activation of apoptosis via activation of caspase-3, a subsequent rise in b- and g- secretase activity, and accumulation of Ab. Isoflurane also promoted aggregation of Ab into plaques. These aggregations of amyloid then promote further apoptosis, and the ‘vicious cycle’ of isoflurane-induced apoptosis and amyloid accumulation is set in motion.

The first statement to make here is that there is no fault to found with the science performed in this article. The research reported here demonstrates that if neuronal cells in culture containing artificially large amounts of APP are subjected to 2% isoflurane for 6 hours, they will lay down amyloid and self-destruct. So far so good. The serious issue here is that the authors extrapolate their findings to infer a serious long-lasting harm to an individual’s brain function. Lest you think I’m exaggerating, all of this group’s original papers and a review they have written within the last few years contain emotive titles suggesting exactly that. Not only are their interpretations of their references a bit dodgy (see above), but there are also other problems. Does the average neuroglial cell see 2% isoflurane for prolonged periods of time? Is it a ‘physiologically relevant’ model of the brain under anaesthesia? They have shown no proof that it is. Furthermore, they have not looked at the effect of any other inhalational (or intravenous) anaesthetic, implying there is a specific problem with isoflurane, whereas the clinical literature I have described above suggests the opposite is true. Do these authors simply hate isoflurane as an anaesthetic agent? I think we should be told. What is even more worrying is their assertion in more than one of their papers that anaesthesia precipitates dementia because prolonged severe hypoxia induces dementia. I don’t know about you, but I try to avoid hypoxia in my patients for any length of time! I don’t see how the authors can seriously suggest this line of reasoning.

So what should we make of all this? The fact that the science was of good quality, and concerned an anaesthetic agent, was enough to get it into high impact journals such as the Journal of Neuroscience and Anesthesiology. It is the implied clinical extrapolation of the research that, in my view, is flawed and dangerous. I hope you will be able to see that the pigeonholers mentioned in the first paragraph got it wrong. There was ‘something to think about’, but this was the misappliance of science, not the supposed dangers of isoflurane. The lesson here: believe nothing, question everything, for the good of your patients.

References

1. Xie Z et al. The inhalation anaesthetic isoflurane induces a vicious cycle of apoptosis and amyloid ß-protein accumulation. J Neuroscience 2007;27:1247-54
2. Verdile G et al. The role of presenilin and its interacting proteins in the biogenesis of Alzheimer’s beta amyloid. Neurochem Res 2007;32:609-23
3. Pearson HA and Peers C. Physiological roles for amyloid ß peptides. J Physiol, Blackwell Publishing 2006;575:5-10
4. Forero DA et al. Synaptic dysfunction and oxidative stress in Alzheimer’s disease: emerging mechanisms. J Cell Mol Med 2006;10:796-805
5. Wirths O et al. A modified b-amyloid hypothesis: intraneuronal accumulation of the b-amyloid peptide-the first step of a fatal cascade. J Neurochem 2004;91:513-20
6. Ohyagi Y and Tabira T. Intracellular amyloid b-protein and its associated molecules in the pathogenesis of Alzheimer’s disease. Mini Reviews in Medical Chemistry, 2006;Vol 6, 10:1075-1080, Bentham Science Publishers
7. Xie Z et al. The common inhalational anaesthetic isoflurane induces apoptosis and increases amyloid b-protein levels. Anesthesiology 2006;104:988-94
8. Xie Z et al. Isoflurane-induced apoptosis: a potential pathogenic link between delirium and dementia. J Gerontol 2006;61A:1300-6
9. Silverstein JH et al. Postoperative cognitive dysfunction in patients with preoperative cognitive impairment. Anesthsiology 2007;106:431-5
10. Moller JT et al. Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study. Lancet 1998;351:857-61
11. Abildstrom H et al. Cognitive dysfunction 1-2 years after non-cardiac surgery in the elderly. ISPOCD group. Acta Anaesthesiol Scand 2000;44:1246-51
12. Bohnen Ni et al. Alzheimer’s disease and cumulative exposure to anaesthesia: a case control study. J Am Geriatr Soc 1994;42:198-201
13. Bohnen N et al. Early and midlife exposure to anaesthesia and age of onset of Alzheimer’s disease. Int J Neurosci 1994;77:181-5
14. Kanbak M et al. The effects of isoflurane, sevoflurane, and desflurane on neurocognitive outcome after cardiac surgery: a pilot study. Heart Surg Forum 2007;10:E36-41
15. Jonsson H et al. Controversial significance of early S100B levels after cardiac surgery. BMC Neurology 2004;4:24-30
16. Kanbak H et al. Propofol offers no advantage over isoflurane anaesthesia for cerebral protection during cardiopulmonary bypass: A preliminary study of S-100b levels
17. Sakai H et al. Isoflurane provides long-term protection against focal cerebral ischaemia in the rat. Anesthesiology 2007;106:92-9
18. Xie Z et al. Isoflurane-induced apoptosis: a potential link between delirium and dementia. J Gerontol 2006;12:1300-6

Antiplatelet Drugs And Perioperative Bleeding: Doesn’t Anybody Care?
Author: Dr Karen Stuart-Smith, Consultant Anaesthetist, Glan Clwyd Hospital, Denbighshire, Wales

Aspirin has been recognised as an important preventative measure in ischaemic heart disease for a very long time¹. The mechanism of action is straight forward: aspirin is a non-specific inhibitor of cyclooxygenase (COX) enzymes. It acts by donating an acetyl group to a specific portion of the COX enzyme (remember aspirin is acetylsalicylic acid)². This is a permanent reaction that cannot be reversed. In low doses (as used clinically), aspirin mainly inhibits COX-1. In platelets this means that

Fig. 1 Arachidonic acid metabolism via the cyclo-oxygenase (COX) pathways. Low-dose aspirin is shown inhibiting the COX-1 pathway. This results in suppression of thromboxane (TX) A2 and prostaglandin (PG) E2 synthesis in platelets. However, the same products can be formed through the COX-2 pathway in an aspirin-insensitive fashion. PLA2 phospholipase A2; EP, PGE2 receptor; IP, prostacyclin receptor; TP, thromboxane receptor. Figure 1 is taken from reference 2, with kind permission from Oxford University Press

the breakdown of cell membrane-derived arachidonic acid to thromboxane A₂, a potent stimulant of platelet aggregation and vasoconstriction, is prevented (figure 1). Higher (pain-relieving) doses are required to block COX-2, so prostacyclin production (a potent vasodilator) is generally preserved in low-dose aspirin therapy (see below for further discussion of this). Thus, in patients with coronary artery disease, aspirin prevents platelet aggregation at sites of endothelial damage, and presumably prevents coronary vasoconstriction at the clot site (although this second effect has, remarkably, never been properly investigated).

Aspirin is an extremely efficient inhibitor of COX-1. Very small doses can cause significant platelet inhibition even in normal subjects³. In cardiac patients a single dose of aspirin has been shown to have a profound effect on platelet aggregation⁴. A daily 75mg tablet is generally prescribed in this country, and 81mg in the USA, but some workers feel that doses as low as 35 mg are appropriate and effective. I should mention aspirin resistance at this juncture. This is a clinical phenomenon characterised by a recurrence of a thrombotic event in spite of continuing aspirin therapy⁵. It is correlated with continuing platelet activity and thus an increased likelihood of clot formation. It is not caused by an incomplete inhibition of COX-1 by aspirin, so cannot be overcome by increasing the aspirin dose. There are a mixture of factors at work, the most important of which is the continuing ability of the platelets to be activated via the ADP pathway, an effect which is blocked by clopidogrel (figure 2)^5,6. However,

Fig. 3 The two receptor model of ADP-induced platelet activation. The thienopyridines, ticlopidine and clopidogrel, inhibit ADP-induced platelet aggregation through active metabolites irreversibly inactivating the P2Y12 receptor. Other antiplatelet agents, such as AR-C69931MX, compete with ADP for binding reversibly to the same receptor. GPCR, G-protein coupled receptor; PLC, phospholipase C; AC, adenylate cyclase. Figure 2 is taken from reference 2, with kind permission from Oxford University Press

except in very specific circumstances^2,7, combined aspirin and clopidogrel therapy is not generally recommended, as the additional reduction in thrombotic events is nearly outweighed by the increased number of major bleeding events⁸. Clopidogrel has an important role to play in lower limb peripheral vascular disease, which discussion I will leave for another day. For the moment I will focus on aspirin.

Overall, aspirin is an extremely effective preventative strategy. In patients at high risk of coronary thrombotic events, long-term antiplatelet therapy reduces the risk of a non-fatal MI, a non-fatal stroke, or vascular death, by 25%². This is a very impressive outcome for any therapeutic agent. High risk is defined as one of the following: stable chronic angina, diabetes, severe hypertension, atrial fibrillation, valve disease, coronary stents, or previous MI². This is a very long list of indications, and just about everyone over 55 has at least one of them. In fact I’m sure we have all anesthetised patients who seem to have all of the above risk factors in one dodgy bundle.

Because low dose aspirin has an extremely good risk profile, as well as being clinically effective, it is very widely prescribed. Unfortunately, the phrase ‘good risk profile’ is a GP and cardiologist definition, i.e. the average patient walking along the street will at the very least come to no harm by taking aspirin, and may derive benefit. Unfortunately no-one has addressed what happens to the risk profile when the patient walking along the street falls over and breaks her hip. Broken hips damage surrounding muscle and result in haematoma formation. If clotting is very efficiently inhibited, it can be predicted that the bleeding will be greater and the haematoma much larger, with the inevitable effect on Hb levels. The hip needs fixing in a very short space of time, so it is not possible, as with elective surgery, to wait for a new uninhibited batch of platelets to be formed. It is likely that this further contributes to the blood loss, and may explain the puzzlingly low Hb in the post-operative fractured neck of femur patient⁹. The increased bleeding tendency is caused by two factors: the reduced platelet aggregability, and the other overlooked issue, which that with thromboxane A₂ (vasoconstriction) inhibited, prostacyclin (vasodilation) is unopposed. This means that not only will a traumatised or surgically vessel not clot, it will not constrict down easily either. The result is a continuing and disheartening ooze.

When originally researching this article I had expected to find a large body of literature on the impact of chronic low dose aspirin on perioperative blood loss, and additional factors such as wound healing. As I have described above, virtually the entire elderly population is on aspirin, and this is the group most likely to have major surgery, both elective and emergency. This includes vascular, general and orthopaedic patients. Although we give strict instructions to patients about stopping aspirin prior to major joint surgery in our elective orthopaedic hospital, my experience is that a large number of these patients either forget to stop the medication, or are on such a large number of prescriptions that they get confused about which one they are supposed to stop. The piece of paper sent home with them on this issue is invariably lost. I suspect that as a result, we operate on a number of people with completely inhibited platelet activity. This is just a guess as no-one has ever researched it. Also, the usual 7 day recommendation for stopping aspirin prior to surgery is a laboratory based calculation. There are no studies in the literature at all to determine whether this is a correlated with platelet activity in real patients¹⁰. I find this extraordinary. Why are the surgeons not interested? The potential for increased blood loss must be substantial, and must, according to all common sense, contribute to post-operative morbidity and increased transfusion rates. However an extensive search of the literature has shown that almost nobody has conducted a relevant clinical trial. Hence the question in the title of this article – doesn’t anybody care?

I expect that a number of you are wondering if it really matters. There are probably no clinical trials because the crux of the matter would be measuring platelet activity in individual patients and correlating it with perioperative blood loss and other post-operative outcomes. This is a tiresome sciencey thing to do and therefore abhorred by anaesthetists and surgeons alike. Before you think I’m being insulting, I should mention that if I had a penny for every anaesthetist that has told me how much they hate basic science and prefer to be a ‘real’ clinical person I’d be a rich woman, etc etc. However at least one company (Haemoscope, Platelet Mapping™) manufactures a thromboelastograph that can provide accurate platelet activity measurements on a very small drop of blood, and is easy to use¹¹, so perhaps the concept will become less frightening.

The real question of course is what do you do with the results of your platelet mapping? Studies in elective patients are desperately needed to sort out the true length of necessary aspirin cessation in a real human being as opposed to platelets in a test tube, so that more accurate pre-operative advice can be given¹². In the emergency patient, a very interesting recent study has shown that the antiplatelet effect of clopidogrel can be reversed in normal volunteers by platelet transfusion. This was in part a laboratory study, but it is of particular interest to me as I have started to give platelets as early as possible to emergency aortic aneurysm repair patients who are usually on both aspirin and clopidogrel. I currently do not have access to a thromboelastograph to assess the efficacy of my treatment (you know, the ‘sciencey thing’), and I’ve only done it on a couple of patients. However as the platelets have to rush down the A55 from Liverpool and this takes an hour, even in the middle of the dark night, I can assess the platelet effectiveness from the relief on the surgeon’s face when the oozing stops. If anyone is interested in making a more formal study of the issue, please let me know. I’d like to think some-one out there cares.

References

1. Experiences with aspirin (Acetylsalicylic acid) in the non-specific prophylaxis of coronary thrombosis. Miss Valley Med J 1953;75:38-44
2. Patrono C et al. Expert consensus document on the use of antiplatelet drugs. The task force on the use of antiplatelet agents in patients with atherosclerotic cardiovascular disease of the European Society of Cardiology. Eur Heart J 2004;25:166-81
3. Hobson AR et al. Antiplatelet effects of licking an aspirin tablet can be detected by thromboelastography. Acute Cardiac Care in press
4. Malinin AI et al. Effect of a single dose aspirin on platelets in humans with multiple risk factors for coronary artery disease. Eur J Pharmacol 2003;462:139-43
5. Frelinger A et al. Residual arachidonic acid-induced platelet activation via an adenosine diphosphate-dependent pathway but cyclooxygenase-1- and cyclooxygenase-2-independent pathway: a 700-patient study of aspirin resistance. Circulation 200;113:2888-96
6. Ohmori T et al. Aspirin resistance detected with aggregometry cannot be explained by cyclooxygenase activity: involvement of other signalling pathway(s) in cardiovascular events of aspirin-treated patients. J Thromb Haemost 2006;4:1271-8
7. Gurbel PA et al. Platelet reactivity in patients and recurrent events post-stenting. Results of the PREPARE POST-STENTING study. J Am Coll Cardiol 2005;46:1820-6
8. Keller T et al. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease. Cochrane Database Syst Rev 2007;18:CD005158
9. Foss NB and Kehlet H. Hidden blood loss after surgery for hip fracture. J Bone Joint Surg Br 2006;88:1053-9
10. Hobson AR et al. Thromboelastography: current clinical applications and its potential role in interventional cardiology. Platelets 2006;17:509-18
11. Bracey AW et al. Impact of platelet testing on presurgical screening and implications for cardiac and non-cardiac surgical procedures. Am J Cardiol 2006; 98 (10A):25N-32N
12. Lecompte T and Hardy JF. Antiplatelet drugs and perioperative bleeding. Can J Anaesth 2006;53(6 Suppl):S103-12
13. Vilahur G et al. Normalization of platelet reactivity in clopidogrel-treated patients. J Throm Haemost 2007;5:82-90

Delivering Anaesthesia To Developing Countries
Author: Rebecca Griffiths, Diamedica Ltd

The Glostavent® Anaesthesia System was originally designed and developed by Dr Roger Eltringham in 1995 as a result of his extensive activities with the WFSA in developing countries. Developing countries provide an awkward mix of circumstances, climate and resource availability in medical situations. Dr Eltringham noticed that oxygen was often scarce and electricity in short supply or subject to unexpected interruptions. The Glostavent® Anaesthesia System was designed specifically to cater for these challenges. “Far too much equipment, whether donated or purchased, ends up in a corner somewhere because the suitability has not been fully taken into account,” said Jan Laursen, Export Director for Diamedica. “This is a terrible waste of precious financial resources, demoralising for medical staff and catastrophic for those who require care.” From the outset there was considerable interest in a machine which could continue to operate in hostile, often isolated, environments and do so safely, economically and simply.

Over the past eighteen months Diamedica Ltd, the company responsible for the manufacture and supply of the Glostavent®, has invested heavily in research and development. “We listen very closely to those who work in the field,” says Robert Neighbour, Managing Director. “We go to many different countries to deliver training and lectures and always come away with new ideas for future upgrades. We always listen. What is the point in designing and manufacturing equipment which simply does not work when it arrives at its destination?”

Current upgrades to the Glostavent® include a larger drawover vaporiser with a capacity of 150ml. The oxygen concentrator can produce 8L of oxygen and 8L of air for the patient’s circuit. This means that almost any patient circuit can be driven.

One of the unique features of the current model Glostavent® is that it will function either as a drawover or a continuous flow machine, the changeover between the two being automatic. In the event of power failure a UPS (Uninterruptible Power Supply) will continue to drive the concentrator for a further ten minutes. After this an on-board oxygen cylinder provides the drive gas for the ventilator at 1/6th minute volume. Assuming an infinite supply of external gas the ventilator will continue to operate on battery for up to 100 hours. Adult and paediatric bellows are fitted as standard on the current model which allows a greater range of tidal volumes.

“We don’t make what we want, we make what they want,” says Richard Tully, engineer. “Anaesthetists working in less than favourable circumstances want a system which does exactly what it says on the tin. The Glostavent® does just that. Just because a machine is simple to operate and maintain does not make it unsophisticated. Although we provide training for users, we have not yet had a problem which we have not been able to fix either on the phone or by email.”

Above: Dr Roger Eltringham Above: The Glostavent® Anaesthesia System

Dr Eltringham, Consultant Anaesthetist at Royal Gloucester Hospital and Vice President of the World Federation of Societies of Anaesthesiologists, uses the Glostavent® in his practice at Royal Gloucester Hospital. His work with the system has been rewarded by an honorary fellowship, given by the West African College of Surgeons. Dr Eltringham travelled to Senegal to receive the award. “I’m absolutely delighted and feel very privileged to be acknowledged in such a way,” said Dr Eltringham. “The Glostavent® is making a very real difference to many countries and, as it becomes more widely recognised, it can only benefit many more.”

It is not just the West African College of Surgeons who are impressed by the Glostavent® Anaesthesia System. “Glostavent® is to anaesthesia in developing countries what Land Rover is to the roads over here”, says Dr Giannino Pittoni from Katana Teaching Hospital in the Democratic Republic of Congo. “We know the Glostavent® delivers wherever the circumstances are difficult,” said Robert Neighbour. “Field trials carried out showed all machines still working after five years in some very hostile environments.”

The Glostavent® is now present in such countries as Malawi, Rwanda, Ghana, Tanzania, the Republic of China, Vietnam and Zambia and is making its debut in Afghanistan and Ethiopia. This takes the number of countries in which the Glostavent® is present up to 20.

“This,” said Dr Paul Cartwright of the Royal College of Anaesthetists, “ is a clever piece of kit.”

The Glostavent® Anaesthesia System can be seen at www.diamedica.co.uk and www.glostavent.com.

The High Risk Obstetric Patient – Anaesthetic Implications
Author: Dr. Mary Korula, Professor, Dept. of Anaesthesia, Christian Medical College, Vellore Tamil Nadu, India

The physiological changes associated with pregnancy makes anaesthetic management of even the normal pregnant patient riskier than non-pregnant patients. Pregnancy is considered “high-risk” when accompanied by any condition unfavourable to the well being of the mother, foetus or both. While in the past, women with medical problems did not survive child bearing age, today we have women with renal and cardiac transplants coming for delivery. Progress in infertility treatment has also led to older women with intercurrent medical conditions achieving full term pregnancies. Anaesthetising these patients is still quite a challenge despite all the advancements in medicine, surgery and anaesthesia.

Medical disorders along with pregnancy

• Morbid obesity
• Asthma and other Respiratory disorders
• Diabetes mellitus
• Congenital or acquired cardiac conditions – MI, Cardiomyopathy, Rheumatic heart disease.
• Chronic renal failure,
• Hematological -ITP, Sickle-cell disease
• Drug abuse

Maternal problems may be related to pregnancy

• Hypertensive disorders of pregnancy (7%) - Pre eclampsia, eclampsia, HELLP syndrome
• Embolism during pregnancy - Venous air embolism, Amniotic fluid embolism, Pulmonary embolism
• Acute Fatty Liver of pregnancy

During labor and delivery

• APH/PPH from placenta previa/abruptio
• Uterine rupture (precipitous labor)
• Uterine atony & inversion
• Placenta accreta & retained placenta
• Intrauterine infection and sepsis

The non-obstetric causes

• Trauma,
• Surgery during pregnancy – laparoscopic, GI- appendicitis, cholecystitis
• Foetal surgery
• Iatrogenic – medication errors and allergies
• Anaesthetic complications

All the above can be accompanied by foetal problems

• Pre and Post-maturity
• Intrauterine growth retardation
• Multiple gestation
• Foetal malpresentations
• Cord compression

In general, anaesthetic management of the high risk parturient is based on the same considerations as in a healthy mother or foetus which would include maintenance of maternal cardiovascular function and oxygenation, improving utero-placental blood flow and delivery of an infant without significant drug effects. This problem is more difficult in the high risk pregnancy because many of these functions are already compromised before anaesthesia. Each of them has specific pathophysiology and treatment may require involvement of the physician and intensivist. One important consideration is that these parturients are on a variety of drugs and treatment, so the anaesthetists should be made well aware of all this before induction of anaesthesia, and they should be familiar with potential interactions between these drugs and anaesthetic drugs and techniques.

Morbid Obesity
Failure to secure the airway and loss of airway due to difficult airways are increased in this group, the incidence of failed intubations in normal parturients is 1:300 vs. 1:2500 in the normal patient. The distortion of airway anatomy, oedema of the upper airway mucosa and tongue, respiratory changes in pregnancy, bleeding due to hypervascularity of airway are all exaggerated in obesity and pre-eclampsia. Skilled help is essential in event of failures. Practice guidelines, Difficult Airway Algorithms and Failed Intubation Drills should be familiar to all anaesthetists. In a “can’t ventilate, can’t Intubate” situation, other options like Awake Intubation, Regional Anesthesia or Local Anesthesia should be employed. The Anaesthetist should be familiar with the newer supraglottic and infraglottic airway devices like LMAs, Combitubes and Transtracheal jet ventilators.Awake intubation can be done with fibroptic bronchoscopes or by direct awake laryngoscopy with good local anaesthesia.

The decreased barrier pressure between the lower oesophageal and intragastric pressure and delayed gastric emptying can increase the incidence of gastro-oesophageal reflux and pulmonary aspiration and its consequences. The increased gastric acidity, muscle relaxation and loss of protective airway reflexes with GA or “Total Spinal” with regional anaesthesia can increase their incidence. The Sellicks manoeuvre or cricoid pressure for rapid sequence intubation in full stomachs to prevent the reflux cannot be applied effectively because of the increased neck tissue and oedema. Aortocaval compression due to the gravid uterus and the supine hypotension syndrome makes it difficult to maintain maternal cardiac output and utero-placental flow. If not prevented and timely corrected, it can result in maternal and foetal mortality. Cardio-pulmonary resuscitation in pregnancy may be difficult due to the lateral positioning and difficult airway. Peri-mortem caesarean delivery is considered when the foetus is viable. The Cardiff Resuscitation wedge is also useful to maintain the tilt and maintain effective CPR.

Regional techniques are the optimal choices to avoid airway problems. Neuraxial blockade like epidurals and spinals can be done as long as there is no contraindication to these and in absence of coagulopathies. They can be initiated early in labor and continued. Walking epidurals are very popular nowadays. Good pain relief can be achieved throughout labor, avoiding the airway problems, neonatal depression and GA even in emergency LSCS if an epidural catheter is sited early in labour. Spinal has quicker onset but can cause precipitous hypotension, though it has been used successfully for years especially in combination with intrathecal opioids like morphine, diamorphine, fentanyl to decrease the LA dosage, prolong the action of LA and decrease the incidence of postdural puncture headache (PDPH). The incidence of PDPH is higher even in normal parturients compared to normal patients. (1.2% even with noncutting Whitacre spinal needles). The advantages of an epiduralblock is the slow onset of action which gives enough time to preload, titrate fluids and vasopressors and maintain pressures while avoiding drastic changes in BP which can be deleterious in an already compromised mother and foetus. It has been found to be safe even in pre-eclampsia and most of the other disorders, if blood pressure is maintained. Patient Controlled Epidural Analgesia (PCEA) is routinely employed with newer LA drugs like ropivacaine and levo- bupivacaine which have lesser motor and cardiotoxic effects. Combined spinal epidural (CSE) is useful especially in late labour to achieve fast pain relief and can be continued as required even for post-op analgesia.

Asthma
This most common respiratory disorder associated with pregnancy can be a nightmare to the anaesthetist even in a nonpregnant patient. Adequate control of asthma during pregnancy is important in reducing potential risks. Goals are improving pulmonary function, by prevention of acute attacks of asthma and its aggressive treatment. Inhaled b2 agonists and corticosteroids have become the norm due to decreased

incidence of systemic side effects. If I/V steroids are used to for control of severe attacks or status asthmaticus, then steroid supplementation just before induction of anaesthesia is required in case of adrenal suppression. But if LSCS is urgent and GA is considered, the b2 agonists can interact with potent inhalational agents like halothane. Though good bronchodilators, they can sensitise the myocardium and cause dysrrythmias. Induction agents like thiopentone can provoke laryngospasm and bronchospasm. We now have better agents like propofol and also bronchodilators like ketamine for induction. Nonhistamine releasing Neuromuscular (NM) agents like vecuronium and not atracurium, opioids like fetanyl rather than morphine or pethidine and also avoidance of NSAIDs which can provoke bronchospasm should be considered. Prostaglandins F are best avoided though PGE are safe. Pseudoephedrine used in bronchospasms can provoke tachycardia and cardiac irritability in the fetus; Short-acting b2-agonists like terbutaline are probably safest.

Epidural analgesia with LA and opioids would be the best choice for labour analgesia and anaesthesia again for all the reasons mentioned above and to prevent irritation of airway. High blocks should be avoided in case they have to be converted to GA which would have to be instituted urgently in less optimal conditions. Many conditions can mimic an attack of bronchospasm under GA from dyspnoea of pregnancy, pulmonary oedema to the dreaded amniotic fluid embolism. Low foetal oxygenation is of prime importance here and systemic drugs to control the attacks like adrenaline has teratogenic effects and b-agonists can precipitate pulmonary oedema. Helium–oxygen mixtures have found to be useful in these conditions. Severe cases would require intubation and ventilation. Non-invasive ventilation may not be possible here due to the gastric reflux problems. If the baseline maternal alkalosis is worsened, foetal hypoxia can develop. Respiratory acidosis develops even with PaCO2 as low as 28-32 mmHg.

Permissive hypercapnia now practised in ICUs for ventilation can cause foetal acidosis and shift to the right of the foetal Hb curve in pregnant patients. Deep plane of Anesthesia is required to prevent laryngo and bronchospasm in these under GA. This may cause difficulties in extubation of these patients.

Diabetes Mellitus
This is another common disorder of pregnancy; perinatal mortality is quite high in this group. Pregestational diabetes has different problems from gestational diabetes. Microangiopathic complications and end organ damage should be actively sought for. Retinal, renal, autonomic neuropathy, hypertension and silent MI are accompaniments. Autonomic neuropathy can cause intractable vomiting and poor metabolic control as also profound hypotension with regionals. Tight glucose controls are mandatory for foetal well being and glycosylated haemoglobin would give an indication of adequate control. b-agonists and steroids, given to prolong delivery and for foetal maturity, can cause insulin resistance, sodium and water retention and hypokalemia with uncontrolled glucose levels. After delivery of baby, insulin doses should be regulated to prevent fatalities from hypoglycaemia as insulin requirements fall rapidly to less than prepregnant doses. Diabetic babies are monitored and treated appropriately. Regionals are very popular, spinal anaesthesia is accepted in most cases with avoidance of hypotension and appropriate fluids.

Cardiac disorders
Though the incidence of rheumatic fever has came down, the proportion of pregnancies with corrected congenital heart disease (CHD) have increased as also the number of women with IHD. Many women are unaware of the cardiac problem until well into pregnancy. The unique problems with these patients are:

• The increase in IV volume which is poorly tolerated when CO is limited.
• Decrease in SVR can increase R to L shunts
• Hypercoagulability mandates need for adequate anticoagulation.
• Anticoagulants increase risk of peripartum haemorrhage and Regional Anaesthesia.
• The marked fluid shifts during labour and delivery is poorly tolerated leading to pulmonary oedema and decompensation.
• Antibiotics for infection and endocarditis prophylaxis is considered.

If valve replacements are required, biovalves or homografts would be best to avoid the need for anticoagulation. Care should be taken to minimise acute changes in BP, PR and blood volume. Venacaval occlusion and decreased venous return is avoided by upright or left lateral position. Prolonged second stage is avoided. Valsalva manoeuvres can decrease CO and increase CVP and SBP. Adequate analgesia required to prevent catecholamine release due to pain and anxiety. Intensive monitoring is continued post-partum as this is a crucial time for cardiac decompensation. Epidural analgesia is given ideally to minimise HR, BP and hemodynamic effects caused by pain and catecholamine release but has to be instituted carefully to avoid decreases in SVR and BP. IV fluids administered with care, rapid hydration and preloading may not be tolerated like normal women, vasopressors may be more usefulephedrine and titrated doses of phenylephrine I/V have been used successfully. Spinal anaesthesia can cause preciptious drop in BP and SVR, so best avoided in cardiac patients. Cardiac stress leading to death occurs in the 3rd trimester, during labor and delivery. These stressful times have to be managed very carefully.

Management is specific for specific lesions. Mitral Stenosis is the most common lesion encountered in our country. Being a relatively fixed cardiac output state, pulmonary oedema can occur, mostly at 28-32 weeks when blood volume is maximum and during labour when fluid shifts are maximum. Intensive monitoring and early treatment of pulmonary oedema are necessary. In atrial fibrillation and patients on anticoagulants with heparin or low molecular weight heparin, epidurals may be a problem. Regionals are contraindicated unless these are electively stopped and guidelines followed especially the timing of epidural catheter insertion and removal or permanent neurological complications can occur. For LSCS, titration of LA dose is essential. Regurgitant lesions like AR and MR are usually well tolerated in pregnancy unlike fixed output and cyanotic conditions. Epidurals would help to reduce cardiac afterload. Bradycardia should be avoided or the regurgitant fraction will increase. MVP is frequently seen but is not much of a problem unless associated with MR. Inhaled NO for increased PVR is helpful. Pulmonary embolism and edema are risks during early post partum and should be monitored. Intensive, invasive monitoring and prolonged ICU care may be required.

Hypertensive disorders of pregnancy
Pre-eclampsia and eclampsia are most dangerous of the hypertensive disorders. Eclampsia is the third common cause of death in pregnancy. PIH patients are on various antihypertensives like methyl dopa, hydralazine or Ca channel blockers. b-blocker therapy leads to IUGR, neonatal hypoglycaemia and hypothermia. Diuretics are best avoided unless super imposed pulmonary oedema ensues. Cerebral oedema and hypoperfusion are causes of cerebral symptoms. Hepatic involvement is common in pre-eclampsia which may affect metabolism and elimination of drugs. Amide LA action may be prolonged; care should be taken with repeated administrations. Prevention of seizures is the goal. This is achieved by magnesium sulphate whose safety has been established but can pose problems for the anaesthetist. Airway oedema due to decreased colloid osmotic pressure and increased intravascular permeability, hypertensive responses to laryngoscopy and difficult intubation are problems. They have generalised vasoconstriction which mandates vasodilatation and titrated volume expansion, rapid correction can lead to pulmonary oedema. Antihypertensives and anticonvulsants may have to be continued upto 12 weeks of delivery. Problems of maternal and foetal hypermagnesemia should be considered, these mandate monitoring and reversal with calcium gluconate if necessary.

Invasive monitoring – arterial, venous, urine output, sometimes even a pulmonary artery catheter is required for fluid and cardiac management. With GA, exaggerated responses to laryngoscopy and hypervascularity can lead to cerebral haemorrhage, laryngeal oedema and airway bleeding. Hydralazine, SNP, GTN, labetolol, MgSO4, Beta and Calcium channel blockers have all been used to obtund these reflexes. All these have foetal effects including short acting Esmolol. MgSO4 can compound hypotension but usually not a problem if monitored carefully. It can potentiate action of NM Blocking drugs; a nerve stimulator for neuromuscular monitoring will help. Ketamine and drugs which increase BP are avoided. They exhibit increased vascular reactivity to catecholamines leading to decrease in placental perfusion. Epidurals have shown to increase intervillous blood flow. They are better choices as they prevent the haemodynamic fluctuations and pulmonary oedema. Decreased platelet counts below 1 lakh(or 80,000) is a contraindication for regionals. The rapidly changing platelet counts are the problem. TEG and coagulation screens may be important but epidural is instituted as soon as platelet counts are available. Spinals may exaggerate hypotension; this can decrease uterine blood flow on an already compromised foetus. Neuraxial opioids along with decreased LA dosage can be used safely.

Patient–controlled analgesia (PCA) intra-venously and inhalational PCA with entonox and inhalational agents like 0.25% isoflurane or 1% desflurane have also been used with good results though sevoflurane seems to attenuate the nitrous oxide effects. These are especially useful in spinal deformities and other surgeries during pregnancy.

Pulmonary Embolism and pregnancy
These patients are on thrombolytic therapy, have had embolectomy and are on IVC filters. Most of them are on anticoagulants, heparin is safe. HIT should be looked for. LMWH is becoming more popular for anticoagulation. Screening for factor Xa activity is not recommended as a routine. Proper guidelines for discontinuation of these before regionals and especially when the epidural catheters are being removed should be considered. Haemorrhage and proper replacement of blood products are essential. In massive PE, right heart strain is common, vasopressors and inotropes may be necessary. Vasoconstictors like adrenaline, noradrenaline and large doses of phenylephrine are best avoided. Amniotic fluid embolism is the most dangerous of these and now referred to as ‘Anaphylactoid Syndrome of Pregnancy’ as it causes multisystem reaction to toxins with lethal consequences, multiorgan failure, DIC and even mortality. Permanent neurological deficits are a possibility, cerebral resuscitation, neuro protection and prolonged ICU care with cardiac and ventilatory support are required. Complications should be best prevented. Pulmonary oedema and haematological abnormalities are main problems. Prompt and aggressive treatment required.

Obstetric bleeding emergencies
The obstetric haemorrhages like PPH, APH, uterine atony may all require emergency hysterectomy for uncontrolled haemorrhage and cause severe hypotension. Intensive, invasive monitoring and prompt volume replacement are most important considerations. Adequate blood products have to be arranged. Placenta accreta and retained placenta would require some uterine relaxation which cannot be possible with regionals alone. GA and uterine relaxation with inhalational agents are usually employed. If a functional epidural is already established, I/V nitroglycerine in titrated doses have been successfully used along with regionals for relaxation of uterus. Similar guidelines as above should be used in other high risk obstetric patients.

Anaesthetic Complications
Though Anaesthesia has become much safer today with better drugs and wider options, anaesthetic complications are still considered the sixth leading cause of maternal death in the US. 50% is due to airway problems with GA, 25% due to complications with regionals. 70% of these are due to epidurals and 30% due to spinals which include LA toxicity and high blocks. 50% of cardiac arrests occur during GA and 7% are thought to occur during regionals. The complication rates are still quite high!

A thorough pre-operative evaluation even in the most urgent cases, optimising the patient as best as possible before anaesthesia, high degree of awareness and suspicion, a great deal of flexibility, alternate options when one technique fails and most of all a good understanding between the anaesthetist and obstetrician are keys to the successful management of these patients.

For Further Reading

1. Critical Illness in Pregnancy in Critical Care Clinics – October 2004;vol 20:4
2. Issues in Obstetric Anesthesia in Anesthesiology Clinics of North America;March 2003
3. Medical aspects of obstetrics – chapter 95 in International Practice of Anaesthesia –vol2. Cedric Prys Robert, Burnell R Brown, John F Nunn.
4. Management of high-risk parturients – section V in Clinical Anesthesia 5th ed– Paul G Barash, Bruce F Cullen, Robert K Stoelting
5. Complicated Obstetric conditions – chapter 58 in Miller’s Anesthesia 2005–Ronald D Miller vol2.

Article used with kind permission from Dr Mary Korula, The Indian Anaesthetists’ Forum, www.theiaforum.org, October issue, 2006.

Association of Anaesthetists of Great Britain & Ireland
Royal Dublin Society, Ireland 12-14 September 2007

Last year the AAGBI celebrated the 50th Annual Meeting and this year is the 75th Anniversary of the Association. There is an attractive and diverse scientific programme scheduled to cater for today’s anaesthetist. Internationally renowned experts will speak at plenary sessions, together with workshops that will provide the latest information on developments in clinical anaesthesia. Basic science and clinical research have also been covered, to encourage continuous improvement in the practice of anaesthesia and patient care.

A new feature of this year’s Annual Congress is a stream of case discussion sessions that are free to delegates. Case reports will be selected for presentation and subject to scrutiny and editorial processes.

The world’s leading pharmaceutical and equipment companies involved in research and development in anaesthesia will demonstrate their new products and innovations during the Industry Exhibition. There will also be the opportunity to attend industry-sponsored seminars.

Let’s not forget the social aspects of the congress. Take time to discover Dublin’s old pubs and modern bars, shop in its thriving markets and malls, and eat in its trendy cafés. Or join in with the social programme with a visit to the Guinness Storehouse and the Annual Dinner at the Royal Hospital Kilmainham.

Click here for the Scientific Programme Overview.

Industry Event & Sponsored Seminars The industry exhibition will be held at the Royal Dublin Society (RDS), in the Main Hall. This provides an excellent opportunity to see first hand the latest products and innovations in the world of anaesthesia. The exhibition will open at 10am on Wednesday 12th and close at 4pm on Friday 14th September. New to the programme this year are Industry sponsored seminars. These will take place in the seminar theatre within the exhibition area in the Main Hall of the RDS. They will run for 20 minute slots during the refreshment breaks. Wednesday 12th September Lunchtime: Session 2: 1305-1325 Sponsored by Javelin Pharmacuticals

Thursday 13th September
Tea break: Session 1: 1040-1100 Sponsored by Janssen Cilag
Lunchtime: Session 2: 1255-1315 Sponsored by Javelin Pharmacuticals
Lunchtime: Session 2: 13.30-13.50 Sponsored by Pentax
Teabreak: Session 4: 15.20-15.40 Sponsored by Intersurgical

Friday 14th September
Lunchtime: Session 2: 1255-1315 Sponsored by Javelin Pharmacuticals

For further information on the congress please visit www.aagbi.org

Out & About In Dublin

Dublin is the capital of, and the largest city in the Republic of Ireland. It is a city steeped in history, and has a rich and varied culture. Dublin plays host to some great entertainment, with several theatres – including the Abbey theatre, the Gate theatre and the Olympia theatre, as well as two large cinemas in the city centre; the Savoy and Cineworld.

Dublin is also famous for its vibrant night-life; the most notorious area is the Temple bar area south of the Liffey, which has become synonymous with tourists, and hen and stag nights. Capture the wonderful Dublin spirit here with it’s many street performers, musicians and drummers.

Take a pleasant stroll along Dublin’s two sister canals, the Grand Canal of Ireland and the Royal Canal. The two canals connect Dublin, in the east of the country, with the River Shannon in the west. Nature enthusiasts can visit the Botanic gardens, which contains over 60,000 pressed plants, or Dublin Zoo, which covers over 30 acres in Phoenix Park and contains 700 animals and tropical birds.

As far as shopping is concerned there’s something for everyone in Dublin. Grafton Street, in the Southside, is the smarter area, with Brown Thomas, the department store showcasing designer fashions, the famous Bewley’s Café and Weirs, the leading jeweller in Dublin.

Along the Northside, Henry Street has many popular highstreet stores, or pay a visit to the well-known outdoor food market of Moore Street.

For those who like their history, Dublin Castle lies in the heart of the city, it was the seat of British rule up to 1922 and is now open to the public, except during state visits.

A trip to this vibrant capital city is not complete without a visit to the famous Guinness® Storehouse. You’ll end up in the Gravity® bar, the highest bar in Dublin. As you relax with your pint, sit back and enjoy uninterrupted 360º panoramic views across the city.

Eating and Drinking...
Chapter One
Basement of Writers Museum,
18 - 19 Parnell Square,
Tel: +3531 873 2266

Restaurant Patrick Guilbaud
21 Upper Merrion street,
Tel: +3531 676 4192
Fax: +3531 661 0052

Les Frères Jacques
74 Dame St,
Tel: +3531 679 4555