Medico Issue 16

Médico July to September 2013

A quarterly publication of GP Liaison Centre, National University Hospital.

MICA (P) No. 018/08/2012

Medical Sp

tlight

A/Prof Tan Huay Cheem Primary Percutaneous Coronary Intervention At NUHCS: -What’s new?

New Anti-Platelet Therapy for Acute Coronary Syndrome

Extracorporeal Membrane Oxygenation (ECMO)

Specialist in Focus: Dr Edgar Tay

02-04 Medical Spotlight • 05-10 Treatment Room • 11-12 Insight • 13-15 Doctor’s Heartbeat

M EDIC AL S PO TLIGHT A/Prof Tan Huay Cheem

Director, National University Heart Centre, Singapore (NUHCS) Associate Professor Tan Huay Cheem graduated from the National University of Singapore (NUS) in 1987 and obtained his Masters of Medicine in Internal Medicine and Membership of Royal College of Physician (United Kingdom) in 1992.

He did his Interventional Cardiology fellowship at Duke University Medical Centre, North Carolina, USA, in 1995. He received Fellowship of American College of Cardiology in 2001, Fellowship of Society of Coronary Angiography and Intervention in 2002 and Fellowship of Royal College of Physician in 2004. He also received Vascular Ultrasonography training at St Vincentʼs Hospital, Sydney, Australia; and carotid stenting at Taiwan National University Hospital.

He is presently a Senior Consultant in the Cardiac Department at the National University Hospital (NUH), Singapore. His concurrent appointments are Director, NUHCS and Associate Professor, Yong Loo Lin School of Medicine, NUS. Prof Tan is regularly invited as lecturer and faculty in many international cardiology meetings. He is also an active clinical researcher and is a visiting professor to several hospitals in China.

Email: huay_cheem_tan@nuhs.edu.sg

Primary Percutaneous Coronary Intervention At NUHCS: -What’s new?

There has been a steady rise in the incidence of acute myocardial infarction (AMI) in Singapore. Data from the Singapore Myocardial Infarction Registry (SMRI) showed that the incidence of heart attacks has increased from 6815 in Year 2007 to 7813 in Year 2011. The crude incidence rate was 248 and 271 per 100 000 in Year 2007 and 2011 respectively. Between the 2 types of AMI – namely, non ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI) – the increase has been seen mainly in the former. The number of patients with NSTEMI and STEMI in Year 2011 were 5048 and 2100 respectively. Among the patients with

STEMI, 67.9% received reperfusion therapy; and the majority (99%) underwent primary percutaneous coronary intervention (PPCI). The 30-day mortality rate for STEMI patients has also dropped from 15.9% in 2007 to 14.3% in 2011. What is even more significant is that the 30-day mortality is found to be lower for those who received PPCI: from 7.0% to 4.9% in the same time period.

There are two important reasons for the reduction in mortality for patients with STEMI. Firstly, it is the widespread adoption of primary PCI as the primary modality of reperfusion therapy.

Nowadays, almost every patient who is admitted to a public hospital within 12

Team NUHCS with Health Minister (from left): Minister Gan Kim Yong, Assoc Prof Tan Huay Cheem (Director & Senior Consultant, NUHCS), Assoc Prof Shirley Ooi (Senior Consultant, Emergency Medicine Dept (EMD), Dr Edgar Tay (Consultant, NUHCS) & A/Prof Ronald Lee (Senior Consultant, NUHCS)

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hours of the onset of his symptom will receive emergency coronary angiography and stenting, if clinically indicated. The other reason is the timely delivery of the PPCI Service. While the timing at which the patient presents himself to hospital is less controllable, hospitals can ensure efficient and prompt provision of PPCI by reducing the time taken to effect the treatment, the so-called door-to-balloon (D2B) time. D2B time is an internationally-adopted parameter to track if the care processes within the hospital that provides this emergency service is up to par. This is uniformly low in Singapore.

effective treatment. This treatment is obviously available in the attending ambulance. There are many reasons for this reluctance to call for an ambulance, foremost of which is cultural. Asians may consider it ‘embarrassing’ to activate the ambulance service and to disrupt the peace of the whole neighbourhood. Or patients may be ignorant of the severity of their symptom, or do not know how to activate the emergency service. The ambulance and the attending medical personnel are able to perform emergency resuscitation such as external chest compression, defibrillation, activate the emergency cardiac team at

the nearest hospital, so that the team can be ready even before the arrival of the patient in the Emergency Room.

Adopting Innovative Technology @ NUHCS NUHCS is an early adopter of innovative technology to enhance the care and treatment of her patients with STEMI undergoing PPCI. This includes not just the coronary revascularization procedure performed by the interventional cardiologist but also the resuscitation procedure performed at the A&E and the cardiothoracic surgical support available.

At NUHCS, we performed 434 cases of PPCI in Year 2012, making us the highest volume centre in Singapore for treating patients with STEMI. Ours is a well-oiled system with efficient and timely delivery of care and good clinical outcomes. A total of 9 interventional cardiologists, backed by a well-trained nursing and allied health team, provide round-the-clock emergency PCI service with a median door-to-balloon time of only 60 minutes, which is well within the international recommended time of less than 90 minutes. In fact, NUHCS was instrumental in leading a nation-wide awareness and push to lower D2B time for PPCI and was awarded the National Medical Excellence Award (NMEA) 2011 for its effort.

Push for Early Medical Access One of the keys to survival in a heart attack situation is the access to medical care. Here, it is not just early arrival in hospital, but also the pre-hospital care delivery. In a study conducted at NUH, it was noted that Singaporeans go to hospitals in ambulances in only 35% of cases. The majority of patients make their own way either by public transport or self-drive. One of the potential causes of death during heart attacks is the onset of malignant arrhythmia such as ventricular fibrillation. In such a situation, direct current electric cardioversion is the only mode of

The Straits Times, 1 June 2012.

The Straits Times©Singapore Press Holdings Limited. Reproduced with permission.

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LUCAS Chest Compression System This is a system that is currently being used at NUH Emergency Medicine Department for patients who have suffered a cardiac arrest and require continuous chest compression. It is designed to deliver uninterrupted compressions at a consistent rate and depth to facilitate the return of spontaneous circulation (RSOC). It delivers automated compressions and free up medical personnel to perform cardiac evaluative and other resuscitative measures. Defibrillation can be performed during ongoing chest compressions. The machine provides effective, consistent and uninterrupted compressions, maintains good blood flow, and increases operational effectiveness, at the same time keeping medical personnel safe during CPR.

cannula into the right common femoral vein, which drains out the blood and oxygenates it externally before returning it to the arterial system via the common femoral arteryy. ECMO can provide acute support in cardiogenic shock or cardiac arrest in patients, assuming that the brain function is normal or only minimally impaired, till the patient recovers or receives a long-term ventricular assist device as a bridge to cardiac transplantation.

The Blanketrol will be set automatically to achieve a goal body temperature of between 32ºC and 34ºC. Cooling is done rapidly in order to achieve maximal effectiveness. After target temperature is achieved, the temperature is maintained for 24 hour before rewarming starts.

During the process of cooling, sedation is achieved using a combination of intravenous Midazolam 2 to 5mg/hour and Fentanyl 25-75 mcg/hr. We have had several success stories in which patients with cardiac arrest recovered fully without any neurologic deficit.

The successful treatment of patients with AMI requires the set-up of a coordinated STEMI network in the country – with pre-hospital triage, early activation of the catheterization laboratory in preparation for emergency procedures before the patient’s arrival, expert care by a team of cardiologists backed up by the cardiothoracic surgeon.

At NUHCS, we strive to provide the best possible care for our heart attack patients with the latest technologies.

Venous blood is drawn centrally and oxygenated externally before being returned to the arterial system in the VA-ECMO system

Hypothermia Therapy Lucas chest compression system being used during resuscitation process at NUH A&E

Extra-Corporeal Membrane Oxygenation (ECMO) As one of two public hospitals in Singapore that has cardiothoracic surgery support, NUHCS is able to provide intensive cardiac and respiratory support to the most severely ill group of patients with heart attack, namely those with cardiogenic shock. Extra-Corporeal Membrane Oxygenation (ECMO) is a procedure performed by the cardiothoracic surgeon who inserts a

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For patients with out-of-hospital cardiac arrest, studies have shown that therapeutic hypothermia has become the foundation for improvement of neurologically favourable survival after cardiac arrest. It is an important adjunct to reperfusion therapy for all resuscitated cardiac arrest victims with suspected AMI. Such an approach can double long-term survival rates among those successfully resuscitated after out-of-hospital cardiac arrest.

At NUHCS, all patients after emergency coronary intervention for cardiac arrest will be cooled using a blanket called Blanketrol placed under the patient.

Portable hypothermia machine

T R EATMENT R OO M Dr Mark Chan

Consultant, Cardiac Dept, National University Heart Centre, Singapore (NUHCS) Dr Mark Chan is a cardiologist at the National University Hospital, Singapore, and an Assistant Professor at the Yong Loo Lin School of Medicine, National University of Singapore.

He obtained his Master of Health Science degree from Duke University in 2008. He then spent another 18 months at the Montreal Heart Institute doing a combined fellowship in interventional cardiology and platelet biology.

He has authored or co-authored more than 60 papers in peer-reviewed journals, including JAMA, Circulation and the European Heart Journal. He has been the principal investigator of multiple large outcome studies in acute coronary syndromes, the principal investigator of two Phase I studies on a novel anti-thrombotic agents and is an associate editor of the International Journal of Cardiology, editorial board member of the American Heart Journal and Deputy editor of the ASEAN Heart Journal.

Email: mark_chan@nuhs.edu.sg

New Anti-platelet Therapy for Acute Coronary Syndrome Clopidogrel, a platelet P2Y12 receptor antagonist, is frequently combined with aspirin, another platelet inhibitor, to treat patients with acute coronary syndrome (ACS) and patients undergoing percutaneous coronary intervention (PCI). This combination of 2 anti-platelet drugs acting via 2 different platelet receptors is frequently termed dual anti-platelet therapy (DAPT) and has been shown to reduce major adverse cardiovascular events (MACE) by 20% compared with single antiplatelet therapy with aspirin.

However, there is wide variability in the level of platelet inhibition with clopidogrel, which is attributable in part to differential bio-activation of the parent compound by the hepatic p450 enzyme system. Carriers of loss-of-function polymorphisms of CYP2C19, namely, the *2 and *3 allele, produce lower levels of the active metabolite of clopidogrel compared with non-carriers, resulting in a decreased anti-platelet effect, and therefore, carry an increased risk of major adverse cardiac events after stent implantation.

NUHCS and other centres have shown that Asian populations have a known higher prevalence of CYP2C19 loss-of-function polymorphisms compared with white populations. While the CYP2C19*2 polymorphism is found in both white and Asian populations, the CYP2C19*3 polymorphism is found almost exclusively in Asian populations.

Lilly) and ticagrelor (Brilinta®, Astra Zeneca). Both agents, in combination with aspirin, have been tested separately in large phase III trials of patients with ACS and have been associated with a 20% relative risk in MACE compared with clopidogrel and aspirin. Of note, the combination of ticagrelor and aspirin was associated with a reduction in mortality, when compared with clopidogrel and aspirin, while the combination of prasugrel and aspirin was not associated with mortality reduction.

NUHCS and other centres have shown that Asian populations have a known higher prevalence of CYP2C19 loss-of-function polymorphisms compared with white populations.

While the CYP2C19*2 polymorphism is found in both white and Asian populations, the CYP2C19*3 polymorphism is found almost exclusively in Asian populations.

Newer and more potent drugs targeting the platelet P2Y12 receptor inhibitor that are not susceptible to differential hepatic activation include prasugrel (Effient®, Eli

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The greater efficacy of the newer platelet P2Y12 antagonists can be attributed to their superior inhibition of platelet activation and aggregation. But this superior inhibition of platelet aggregation leads to a greater impairment of haemostasis, and consequently, a higher risk of major bleeding. While both prasugrel and ticagrelor have been shown to increase the risk of major bleeding compared with clopidogrel, ticagrelor is associated with an increased risk of intracranial haemorrhage while prasugrel is not.

Studies are ongoing to assess the efficacy and safety of single anti-platelet therapy without aspirin as a means of maximising the benefits while reducing bleeding risk. A further disadvantage of ticagrelor is that it has to be administered twice a day compared with

once a day for clopidogrel and prasugrel; compliance may therefore be a greater concern for ticagrelor.

Cost is another concern of the newer platelet P2Y12 antagonists as generic clopidogrel costs 50 cents a day while prasugrel costs $5 a day and ticagrelor costs $6 a day. However, because DAPT is typically prescribed for a year after ACS, prescription costs may be less of a concern at the individual level but nonetheless, it can have significant economic implications when considered at the healthcare systems level.

In Markov model cost-effectiveness analysis by our NHG colleagues using clopidogrel as the base-case comparator, the incremental cost effectiveness ratio (ICER) per quality-adjusted life year

Figure 1. Antiplatelet Algorithm in ACS (adapted from Newby, L K) Legend ASA CYP3A4 inhibitors DC ICH PCI STEACS TIA

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Acetyl salicylic acid Protease inhibitors, macrolide antibiotics and azole antifungals Discharge Intracranial haemorrhage Percutaneous coronary intervention ST-elevation ACS Transient ischaemic attack

(QALY) for ticagrelor and prasugrel was comparable – at SGD18,647 versus SGD18,921 respectively. Probabilistic sensitivity analysis indicated that ticagrelor and prasugrel had more than 85% probability of being cost-effective, based on a willingness-to-pay threshold of one GDP per capita or SGD63,505 per QALY (Zhang YJ et al, 2013, personal communcation).

At the NUHCS, we have therefore developed an algorithm for use of the newer P2Y12 antagonists based on the totality of the data (Figure 1). We envision that this algorithm will maximise MACE reduction while minimising bleeding risk.

T R EATMENT R OOM A/Prof James Yip

Senior Consultant, Cardiac Dept, National University Heart Centre, Singapore (NUHCS) A/Prof James Yip is currently a Senior Consultant in the Cardiac Department of the National University Heart Centre, Singapore (NUHCS). He also holds the positions of Chief Medical Information Officer, National University Health System (NUHS), Programme Director for Congenital/ Structural Heart Disease in NUHCS and is an Associate Professor in the Department of Medicine in the Yong Loo Lin School of Medicine, National University of Singapore (NUS).

A/Prof James Yip graduated from NUS in 1991 and has been a Fellow of the Academy of Medicine Singapore since 2001. He was trained in adult cardiology at the National University Hospital, Singapore, from 1995 to 2001, and was a clinical fellow at Toronto Congenital Cardiac Centre for Adults from 2001 to 2002.

His interests include pregnancy and heart disease, pulmonary hypertension, Marfan syndrome and medical informatics. He is also a pioneer in percutaneous cardiac structural interventions for cardiac septal defects, left atrial appendage occlusion devices, closure of prosthetic paravalvular leaks, mitraclip device therapy and aortic valvuloplasty.

Email: james_yip@nuhs.edu.sg

Left Atrial Appendage Device Closure : Its role where anticoagulation is not suitable in patients with atrial fibrillation (AF) Patients with atrial fibrillation (AF) have a 5-times increased risk of developing stroke compared to those without. 87% of strokes are thromboembolic in origin, for which 90% of these arise from the left atrial appendage (LAA). The primary treatment of high risk AF patients is the use of traditional anticoagulants, like warfarin, and more recently, with novel anticoagulants (NAC) (like Dabigatran and Rivaroxiban) to prevent blood clots from forming in the heart.

However, long-term anticoagulation therapy is not without issues. Warfarin therapy requires frequent blood

monitoring requirements (INR), dietary restrictions, whilst NAC therapy involves increased cost of medication, side effects, lack of antidote in cases of serious bleeding and lack of protection due to short-term non-compliance.

When patients have a bleeding complication, both therapies may not be suitable. 50% of patients with AF who are eligible for anticoagulation therapy are not on any therapy or on inadequate therapy (anti-platelet therapy) for stroke prevention, some of them due to increased risk of bleeding or history of hemorrhages.

The Watchman Left Atrial Appendage (LAA) Occluder

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The WATCHMAN LAA closure device is designed to close off the left atrial appendage – which is a major source of clots in patients with AF, to reduce the risk of stroke, eliminating the need for long-term use of blood-thinning medications.

The original PROTECT AF Trial (Lancet 2009; 374: 534–42) showed a primary efficacy event rate of 3.0 per 100 patients in the intervention group and 4.9 per 100 patient-years in the control group. This showed the short-term equivalency of the intervention with warfarin therapy.

In a recent analysis of the 4-year outcomes in the PROTECT AF Trial, long-term therapy with the WATCHMAN device was superior to warfarin for both primary efficacy and also mortality. The observed primary efficacy event rate was 2.3% and 3.8% in the intervention and control groups respectively, demonstrating a 40% relative risk reduction in primary efficacy in the WATCHMAN group.

The Aspirin-Plavix Feasibility Study with Watchman LAA (ASAP Registry) showed that the Watchman LAA device can be safely implanted in patients who are contraindicated to warfarin therapy. The stroke event rate of 1.7 per 100 patient-years in ASAP compares favorably to PROTECT-AF with 2.2 events per 100 patient-years despite the difference in CHADS2 score distribution.

Transesophageal Echocardiogram of the Watchman LAA device being deployed in the left atrial appendage.

1. Patients with high risk AF who are uncomfortable with life-long systemic anticoagulation therapy because of an increased risk of falls or bleeding.

2. Patients with high risk AF who have already suffered a major bleed due to anticoagulation therapy but are suitable for long term anti-platelet therapy.

3. Patient who require long term double anti-platelet therapy (e.g. drug eluting coronary stents) but addition of an anticoagulant for high risk AF would significantly increase the risk of bleeding.

The current procedure-related complication rate for the WATCHMAN LAA device is 3.7% (ASAP Registry) and 4.4% (PREVAIL Trial) with serious pericardial effusion, accounting 2.2% of cases (Circulation. 2011;123:417-424).

As there is a one-time procedure-related risk for any intervention, this has to be weighed against the ongoing risk of bleeding which may be 2-3% per year for anticoagulants.

Our first patient who was implanted on 20th October 2009 had these characteristics. This particular patient had atrial fibrillation and a history of prior stroke with hemorrhagic conversion. After initial transesophageal echocardiography (TEE) which confirmed a favourable LAA anatomy, we performed a trans-septal puncture under general anaesthesia in the cardiac catheterization lab with initial vascular access through the femoral vein.

Thus, patients who may benefit the most from having LAA occlusion as a primary intervention would be :

The Watchman LAA device was deployed in the left atrial appendage under TEE and fluoroscopic guidance. The patient

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Fluroscopic image of the Watchman device deployed

was able to ambulate the same day after the procedure and was discharged on both warfarin and anti platelet therapy. About 7 weeks after the procedure, another TEE was performed to check the seal of the Watchman device. Warfarin was then withdrawn and the patient continued on long-term anti-platelet therapy alone.

In conclusion, LAA occlusion with the Watchman device is a useful adjunct in patients with AF who may not be suitable for long term anticoagulation.

The long term data for device therapy shows superiority to anticoagulation therapy with an acceptable procedural complication rate.

T R EATMENT R OOM Dr Andre Cheah

Common Bites to the Hand

Consultant, Dept of Hand & Reconstructive Microsurgery, University Orthopaedics, Hand & Reconstructive Microsurgery Cluster Dr Andre Cheah was awarded the College of Surgeons Gold Medal for Hand Surgery in 2010. His clinical interests include joint problems of the hand and wrist and he is an advocate of minimally invasive and endoscopic surgery. He is involved in collaborative basic science research in biomechanics and anatomy and is published on the proximal interphalangeal joint.

Dr Cheah is interested in healthcare delivery systems and works closely with members of the industrial design community to propose device solutions to aid in clinical practice. He completed his MBA at INSEAD in 2012.

Email: andre_ej_cheah@nuhs.edu.sg

Introduction Bites from our pets are becoming increasingly common as rising affluence allows more people in Singapore keep animals such as dogs and cats. While some may argue that humans are not animals, some of us put paid to this viewpoint by taking part in less than wholesome activities such as skirmishing, sustaining a ‘fight bite’ in the process. Hand surgeons see a good number of both these types of bites, both in the acute setting as well as those with delayed presentation after initial sub-optimal treatment.

Epidemiology Dog and cat bites There are approximately 55,000 dogs in Singapore and about 70 reports of dog attacks in 2009 though the actual figure is likely to be much higher as many pet owners may not report bites from their own dogs. While there are no local figures, a recent report estimates that dog bites affect 1.5% of the population in the USA annually. There is less information on the pet cat population but it would not be unreasonable to say that it may be close to that of the dogs.

Suffice to say, bites from dogs and cats are not a trivial problem in terms of patient numbers. Even more significantly, another report showed that the difference in costs of dog and cat bites managed optimally in the initial setting with measures that included intravenous antibiotics and surgical debridement was far cheaper than management of complications such as osteomyelitis after inadequate initial treatment (US$17000 versus US$77000).

As such, it would make good clinical as well as economic sense to provide the best treatment from the outset.

Human bites Human bites usually take the form of fight bite which is not only sustained during unsavory but also accidentally during contact field sports. Incidence has been reported in a New York study at 11.8/100000 population per year though under-reporting is the norm as many involved in altercations may not admit to the mechanism of injury due to a combination of embarrassment and fear of legal consequences.

A fight bite with tendon and joint injury.

Clinical Manifestations Tissue injury Crush injury, lacerations and abrasions are common in dog bites as their teeth and jaws are designed to crush and tear their prey. These wounds on top of being inoculated with bacteria will have devitalised tissue which needs surgical excision. Cats, in contrast, usually inflict puncture wounds as they have long, slender incisors that can penetrate deeply into tendon, bone and joints.

These wounds tend to be underestimated because they are small and seal off early. In fact, deep abscesses and osteomyelitis are more common in cat than dog bites as is infection rate.

Significantly, human bites have a higher complication and infection rate than animal bites. This is especially so in fight bites for several reasons. First, these injuries occur over the dorsal aspect of the metacarpophalangeal joint where teeth can easily penetrate skin, tendon, joint capsule, articular cartilage and even bone. Second, this contamination sustained when the fist is clenched then gets dragged proximally into the dorsum of the hand when the fist is opened, thereby spreading the bacteria over a

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References wider area. Third, extensor tendon and articular cartilage are relatively avascular structures that have limited ability to fight infection. Fourth, there is a high concentration of pathogenic organisms in human saliva. Lastly, patients tend to present later because they underestimate the injury and are uncomfortable with the potentially law breaking circumstances surrounding their injury.

Radiographic examination is a must to look for foreign bodies in the form of animal teeth parts and assess integrity of the bone cortices whose absence may indicate penetration to the bone. Dog and human bites are usually polymicrobial with a mixture of aerobes such as Pasteurella sp, Eikenella corrodens, Staphylococcus sp and Streptococcus sp and anaerobes while cat bites Pasteurella multiocida is the main isolate in cat bites.

procedure under general anaesthesia so as not to spread the inoculums by wound infiltration with local anaesthetic.

Antibiotic and tetanus prophylaxis Amoxicillin-clavulanic acid is the mainstay of prophylaxis as it provides excellent coverage against the usual organisms that are inoculated.

Doxycycline with metronidazole is a good alternative in penicillin-allergic individuals. While the oral route has been recommended as sufficient, intravenous antibiotics is the rule for patients managed by us for the increased bio-availability and non-interference with patient fasting for general anaesthesia. Tetanus booster is a must if original three-dose series has been given but none in the past year prior to the bite.

Repair of damaged tissue

1. Wong T. Dog attacks on the rise. The Straits Times 19 Nov 2009.

2. Gilchrist J, Sacks JJ, White D, Kresnow MJ. Dog bites: still a problem? Inj Prev 2008; 14: 296-301.

3. Benson LS, Edwards SL, Schiff AP, Williams CS, Visotsky JL. Dog and cat bites to the hand: treatment and cost assessment. J Hand Surg Am 2006; 31: 468-473.

4. Marr JS, Beck AM, Lugo JA. An epidemiological study of the human bite. Public Health Rep 1979; 94: 514-521.

5. Fleischer GR. The management of bite wounds. N Engl J Med 1999; 340: 138-140.

6. Perron AD, Miller MD, Brady WJ. Orthopedic pitfalls in the ED: fight bite. Am J Emerg Med 2002; 20: 114-117.

7. Dendle C, Looke D. Review article: animal bites: an update for management with a focus on infections. Emerg Med Australas 2008; 20: 458-467.

8. Oehler RL, Velez AP, Mizrachi M, Lamarche J, Gompf S. Bite-related and septic syndromes caused by cats and dogs. Lancet Infect Dis 2009; 9: 439-447.

9. Center for Disease Control and Prevention. Travelersʼ health yellow book on Rabies. wwwnc.cdc.gov/travel/yellowbook/2010/chapter-2/rabies.aspx (accessed on 12 Sep 2010).

Management Clearance of contamination “There are two types of bites in general.

First is the one you debride and second is the one you wish you had debrided.”

This adage, drummed into us doyens of our community, sums up the first and arguably most important principle in the management of bites. This is especially true in the hand where 30-40% of bites become infected. The reason for this is the many tight and enclosed spaces that exist to allow inoculated bacteria to fester as well as the proximity of bone and joints to the skin, making them more susceptible to penetration by teeth. Timely and crucial surgical treatment involves excision of all tissue that is devitalised and most tissue that has been inoculated by the animal’s teeth including curettage of affected bone and lavage of joints that have been breached. Provided the patient is fit enough, the preference is to perform this

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Structures, including skin injured by the bite will need to be repaired. However, in the face of the intrinsically high infection risk linked to bites, placement of internal fixation in fractures and suture material for tendon, nerves and skin will no doubt exacerbate this risk and should be deferred until the wound is deemed clean after at least one adequate surgical debridement. In other words, all reconstruction is staged except vascular repair in the face of a devascularised part.

How about Rabies?

Rabies virus is present in the saliva of the biting animal and has to be taken up by the nerve synapses to travel to the brain where it can cause fatal encephalitis. The hand, along with the face, has a large number of nerve endings and hence is considered a higher risk exposure when the biting animal is infected with rabies.

Fortunately, the latest data in 2005 from

the Centers of Disease Control and Prevention place Singapore on the list of countries that report no indigenous cases. As such, it is reasonable to omit rabies prophylaxis if the patient has been bitten by an animal in Singapore.

Have we gotten away with doing less?

While we definitely do not advocate anything less than prophylactic antibiotics, tetanus prophylaxis and surgical debridement, anecdotes of less optimal treatment being carried out without subsequent serious infection taking place have been told.

Nonetheless, such a strategy is unpredictable at the very least and is, in fact, potentially disastrous.

I NSIGHT Dr Matthew Cove

Associate Consultant, Dept of Cardiac, Thoracic & Vascular Surgery (CTVS), National University Heart Centre, Singapore (NUHCS) Dr Matthew Cove graduated from Leicester Medical School in England in 1999. He completed his post-graduate internal medicine training at Providence St Vincent, Portland Oregon, in the United States, where he was first exposed to critical care medicine. He then practiced internal medicine with the Mayo Health System in western Wisconsin for two and a half years, before undergoing further training in critical care medicine. He completed a fellowship in critical care medicine at the University of Pittsburgh in the United States and then moved to Singapore to practice as an Intensivist. During his time in Singapore and Pittsburgh, Dr Matthew Cove became interested in the clinical application of extracorporeal technology in critically illness, as well as the research implications.

Email: matthew_edward_cove@nuhs.edu.sg

Extracorporeal membrane oxygenation (ECMO) is one of the new, hot topics in the management of the critical ill. ECMO provides support to adult patients with respiratory failure, or cardiogenic shock, refractory to conventional support strategies. It is also used in children, particularly for conditions such as primary pulmonary hypertension of the new born and congenital heart disease.

However, it is not without controversy and it may be surprising to learn that the technology is not especially new; ECMO was first successfully used in 1971. The concept is ingeniously simple – blood is removed from the body via a large cannula placed into a central vein, pumped through an oxygenator, where oxygenation and decarboxylation occurs and then returned to the body. In veno-arterial ECMO (VA-ECMO), blood is returned to an artery (Figure 1) and in veno-venous ECMO (VV-ECMO), blood is returned via a vein (Figure 2).

Returning blood through an artery provides both circulatory and respiratory support and is most suitable for

Extracorporeal Membrane Oxygenation (ECMO)

Figure 2: VV-ECMO, deoxygenated blood is removed from a femoral vein, pumped through an oxygenator and the oxygenated is then returned via the other femoral vein or the superior vena cava.

Figure 1: VA-ECMO, deoxygenated blood is removed from a femoral vein and returned to a femoral artery after being pumped through an oxygenator.

circulatory failure, whereas VV-ECMO provides only respiratory support.

Although the concept is simple, the provision of ECMO requires a multi-disciplinary team that is composed of perfusionists, specially trained nurses, intensivists and cardiothoracic surgeons.

Despite being available for over 40 decades, acceptance of ECMO had a slow start. After the publication of the first successful use in 1971, there was an initial flurry of excitement. The National Institute of Health (NIH) in the USA quickly funded a randomised controlled trial of ECMO in acute respiratory distress syndrome (ARDS). The results were published in 1979; and disappointingly, no improvement in outcomes was demonstrated (Figure 3).

However, this reflected a misunderstanding of ECMO and ARDS at the time; perhaps not surprising since ARDS was a relatively new disease first described in 1967.

Following the NIH trial, many clinicians lost interest in the technology but one clinician, Robert Bartlett, refused to believe ECMO had no future. He sought out the optimal patients for ECMO – neonates who developed respiratory distress due to pulmonary hypertension of the new born.

By using ECMO in these patients he demonstrated a survival improvement from barely 10% to over 75%.

However, it took several small trials and a large, randomised controlled trial in the UK to convince the larger medical community.

Indeed, this dramatic jump in survival is often cited when people consider the

Trial

Survival With ECMO

Survival without ECMO

Zapol et al 1979 1 Peek et al 2009 2

10% 63%

8% 47%

Figure 3: Trials using ECMO in adult acute respiratory distress syndrome

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ethics of randomised controlled trials in the face of such impressive changes in outcome.

The impressive outcomes in neonates and children, primed the larger critical care, cardiac and cardiac surgery community to take notice; and over the past four to five years, we have a seen a proliferation in ECMO use. Two recent events have provided the largest driving force – the H1N1 pandemic in 2009-2010 and the concomitant reporting of a trial where adult patients with ARDS were randomised to conventional ventilator therapy or transfer to an ECMO centre.

This trial, also called the “CESAR” trial, found that ARDS patients referred to an ECMO centre were not only more likely to survive, but also had less disability following their critical illness (Figure 3).

At about the same time, the Australian and New Zealand Intensive Care Society (ANZICS) published their ECMO experience in H1N1 patients. They reported a 71% survival in patients who were failing conventional mechanical ventilation after they were placed on ECMO. Similarly, an elegant study in England reported that H1N1 patients with severe ARDS were more than twice as likely to survive their critical illness if they received ECMO. The reason for this survival benefit in patients with refractory respiratory failure is the opportunity VV-ECMO provides for complete lung rest. It is well-recognised that mechanical ventilation can perpetuate the underlying lung injury and damage that resulted in the critical illness in the first place. This has been described as ventilator induced lung injury. Patients on VV-ECMO are no longer dependent on their lungs for gas exchange, allowing use of “rest” ventilator settings.

Indeed, in some centres, patients are taken off the ventilator altogether once they are stabilised on ECMO.

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Unfortunately, the equipment necessary to allow ECMO patients to be managed off the ventilator is currently unavailable in Singapore, but NUHCS is primed to take this next leap once it becomes available.

At NUHCS, we supported several patients with VV-ECMO during the H1N1 epidemic. In addition, we have supported many patients with cardiogenic shock using VA-ECMO. Cardiogenic shock patients fall into two groups – those who need support after complex open heart surgery, including children after correction of congenital heart abnormalities, and those who have had a large myocardial infarction.

The role of VA-ECMO in these patients is to maintain organ perfusion with oxygenated blood and off-load the heart while it recovers from major surgery or a massive myocardial infarction. VA-ECMO allows the heart to “rest” because these patients would otherwise need high levels of inotropes and vasopressors if they were managed without ECMO. Paradoxically, such medications increase oxygen consumption in the struggling heart, perpetuating cardiac ischaemia.

The majority of patients experience a recovery in cardiac function within a few hours or days of commencing VA-ECMO, allowing discontinuation of ECMO as recovery ensues. However, some patients will experience a delayed recovery requiring placement of a more permanent cardiac assist device, once they are stabilised on ECMO. In some patients, the heart may not recover at all resulting in a heart transplant.

ECMO is not without complications, and complications resulting from bleeding are of particular concern. There are two reasons for this; firstly, blood coming into contact with the foreign surface of the ECMO has a tendency to clot. This results in consumption of clotting components and can create a diffuse

References 1. Zapol WM, Snider MT, Hill JD et al. Extracorporeal membrane oxygenation in severe acute respiratory failure.A randomized prospective study. JAMA. 1979;242:2193-2196.

2. Peek GJ, Mugford M, Tiruvoipati R et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentrerandomised controlled trial. Lancet. 2009;374:1351-1363.

intravascular coagulation type of picture.

Secondly, in order to prevent blood from clotting within the circuit, these patients are subjected to anticoagulation with heparin. These factors place patients at risk of hemorrhagic complications.

Bleeding complications have been as high as 60% in some reports, and range from simple cannula exit site bleeding to the much feared intracranial bleeds, which affect up to 12% of patients.

Improvements in biocompatibility are reducing the bleeding risks, but they still remain significant. Other complications include failure of circuit components, infection and problems related to the underlying critical illness.

NUHCS has built a team of cardiac surgeons and intensivists who have a special interest in ECMO. In addition, we have a team of specially trained nurses and perfusionists to support the programme. We also run bi-annual workshops to train and accredit staff who work with ECMO patients. As a result, the number of patients receiving ECMO has increased from 0-2 per year to 20-25 per year over the past five years.

We are proud that we can provide this support to respiratory failure patients and cardiac patients of all ages. As our team grows, and our outcomes continue to improve, we anticipate that many providers in the community will come across our ECMO survivors within their practice in the community.

D OCT OR ʼ S H EAR TBEAT Dr Edgar Tay is a practicing cardiologist at the National University Heart Centre, Singapore (NUHCS), and an Assistant Professor at the Yong Loo Lin School of Medicine, National University of Singapore. Dr Tay obtained his Master of the Royal College of Physicians (UK) diploma in 2004, and completed his cardiology training at the National University Hospital, Singapore, in 2008.

He obtained the Ministry of Health’s scholarship to undergo sub-specialty training in Adult Congenital Heart Disease and Pulmonary Hypertension at the Royal Brompton Hospital, London, UK and then completed a second year of interventional fellowship at St Paul’s Hospital, Vancouver BC, where he was trained in transcatheter aortic valve implantation.

He is also active in academia and has written widely in peer-reviewed journals and presents regularly at international scientific meetings. He is also accredited by the European Society of Echocardiography for adult congenital heart disease and has written 2 book chapters on echocardiography in congenital heart disease.

Presently, he sub-specialises in the management of patients with heart valve disease and is the co-lead in the TAVI and Mitraclip programmes. He also manages patients with adult congenital heart disease, pulmonary hypertension and those with heart disease in

MBBS, MRCP (UK), MMed (Int Med), FAMS, FESC, FACC

1

Was becoming a doctor always been your ambition?

I came from a Catholic background and was privileged to receive guidance from my parents, the Lasalle brothers and religious sisters early on in my childhood years. Their focus had always been on doing the best I can and using my gifts for the good of the society.

As I grew up and saw what physicians could do, becoming a doctor became much more of a reality. Since my secondary days, I had made it my career choice.

2

Why the interest to specialise in cardiology?

When I completed medical school, I was exposed to varied training and sub-specialties – anaesthesia, oncology, neurology and cardiology.

But as I delved deeper in cardiology, I started to see that the treatment effect in heart patients is often very dramatic. I came across very sick patients, who were on the brink of death, restored to the pink of health – rapidly – and returning to their normal routines after treatment.

The ability to intervene effectively in these patients is rewarding.

Specialist in Focus

Dr Edgar Tay

3

You are trained in interventional cardiology. Could you describe this sub-specialty?

Interventional cardiology is a sub-specialty of cardiology that utilises mechanical techniques to treat heart conditions. This field includes coronary angioplasty (also referred to as stenting or ballooning) as well as structural heart intervention which treats patients with valve disease.

Structural heart intervention is an evolving field. We have been treating patients with congenital heart disease, such as atrial septal defects (hole in the heart), with percutaneous devices for some years. Recently, we have also started to treat many patients with heart valve diseases with transcatheter techniques.

Here in NUHCS, our interventional cardiologists work very closely with our cardiac surgeons. It is a team approach where our heart valve team assesses and

decides the best treatment method for every patient.

4

What are some therapies / procedures that benefit patients with structural heart disease?

Transcatheter Aortic Valve Implantation (TAVI) is one procedure used to treat severe Aortic Stenosis, a condition in which the aortic valve becomes narrowed, obstructing the outflow of blood from the heart and thereby requiring the heart to work harder to pump blood around the body.

One of our success stories is an 85-year-old man with severe aortic stenosis and stable lung disease. His surgeons felt that he couldn’t take open heart surgery safely, so TAVI became a suitable option. A typical hospital length of stay for such a procedure is about 5 to 7 days.

Some patients might also suffer from mitral regurgitation (or “MR”). It is a

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devices which will hopefully translate to useful clinical products for patients.

6

How is it like working in one of our nation’s national heart centres?

Being in an academic medical centre is unique.

condition affecting one of the valves in the heart, called the mitral valve. The mitral valve is located between the heart’s two left chambers (left upper chamber called the left atrium and left lower chamber called the left ventricle) and it allows blood to flow forward in one direction through the heart during a normal heartbeat. When the mitral valve does not close completely, blood flows backward in the opposite (wrong) direction. This backward flow is called mitral regurgitation.

In severe cases, reduced blood flow is pumped out of the heart. This creates excessive workload on the heart leading to dilation of the heart chambers. If left untreated, it can result in atrial fibrillation (irregular heartbeats), stroke and heart failure.

There are currently several options of treatment available for mitral valve regurgitation. These include medical treatment, surgery, or less invasive valve repair such as the Mitra-clip Therapy.

Patients undergoing this procedure experience less pain as it requires only a small puncture in the leg vein. In addition, their stay in hospital is also shortened (about 3 days).

Given the different techniques available to treat patients, our heart valve team will assess each patient and customise treatment therapies in order to maximise patient outcomes.

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5

What excites you about the future of your field here in NUHCS? There are many new techniques and devices in the horizon that are less invasive, and thus, more effective for patients.

We started the Atrial Appendage Closure Device Programme recently – a device that seals the left atrial appendage.

This treatment is for patients who have irregular heart beats called atrial fibrillation which can cause strokes. To protect them from suffering from strokes, the patients should ideally be on blood thinners / anti-coagulations most of the time. However, people like athletes, those with pre-existing bleeding risk (gastric ulcers, tumours), elderly patients who are prone to falls, workers who operate heavy machinery, may not want or may not be suitable for anti-coagulation.

To offer such patients an alternative, we can insert a device into the appendage through a small puncture in their skin.

This device seals or blocks the space (pocket) that forms clots, thereby reducing the risk of clot formation, and therefore, the risk of stroke.

While we bring in new technologies to benefit patients, we are also concurrently working closely with our NUS’ engineering team to develop locally-made

Besides putting in our best efforts in the clinical management of patients, we are also actively involved in teaching and research. In my experience here, my research collaborators and students often ask relevant questions about patient care such as: “How can we do things better than what is available today?”, “Are there more effective and safer alternatives for this patient?”, etc.

Hence, the entire treatment course goes through a more thorough thinking process and this can benefit patients.

I think that we are also developing our synergy as a team very well. Previously as individual departments of Cardiology and Cardiac, Thoracic & Vascular Surgery (CTVS), we used to work more independently. With the formation of NUHCS since 2008, cardiologists and cardiac surgeons are now working much closer together. There is more communication, interaction, and most importantly, team-work. More patient cases are discussed in multi-disciplinary groups or teams. It’s almost like a marriage, harnessing and complementing each other’s strengths.

7

What are some common myths or misconceptions about heart disease?

I think people are getting more informed today due to the internet. So that is a good thing.

However, I do come across a large group of people who are quite averse to ‘western’ medicine. Instead, they prefer alternative medicine such as traditional Chinese medicine, herbal medicine and other forms of treatment – some of which do not have supportive clinical evidence of safety or efficacy. Some of these patients may already be in the advanced stages of disease, but would still refuse effective, life-saving treatment due to their entrenched beliefs.

Another myth is that the elderly doesn’t deserve treatment. Our seniors

sometimes feel that they are old and not deserving of treatment, and as such, limit their own longevity. We did a study recently looking at patients with severe valve conditions. This group of patients would die in 3 years if we didn’t treat them. Among patients whom surgeons felt they had a good chance of treatment and recovery, about 40% of the group above 70 rejected surgery.

The fact is that people in Singapore are living longer because of advanced medical care. We are already seeing an increasing number of patients aged above 80 in our hospital wards. We have also clearly demonstrated that these senior patients who undergo effective treatment would benefit as much as in younger patients.

8

Could you share a memorable experience from your care of patients?

We had this 60-year-old patient who worked as a hawker. He was diagnosed with a heart valve problem, but did not do anything about it for a long while.

About 3 to 4 years later, he suddenly fell ill. He couldn’t eat, had trouble swallowing, lost his voice, and was breathless for many months. Outpatient visits to specialists were all in vain; the specialists couldn’t find any problem with him.

After about 6 months, he developed breathlessness and was brought to the A&E. He was subsequently referred to a cardiologist. By that time, his body mass index had plunged to 18 – he had become very frail and had to move around on a wheelchair. And when our team finally saw him, we found that his heart had become so large that it compressed a critical nerve that controlled the movement of his vocal chords as well as his food tube. This accounted for all his complaints.

However by then, the surgeons could not operate on him as he was too high risk for conventional heart surgery.

We then performed a mitra-clip procedure on him. After just 2 days, his breathing improved and he no longer required his breathing aids. By the third month, all his above symptoms

disappeared. And now he’s recovered completely and doing well.

In the past, we would have no alternative to treat this patient without opening up his chest. This would often mean terminal care.

As for my professional roles, I feel that teaching and treating are intertwined. They are all part and parcel of being a doctor – as I treat patients, I find opportunities to teach our next generation of doctors. I had the privilege of having learnt from past mentors and tutors and I am doing likewise now.

9

How do you balance your different roles as a husband, father, physician, teacher?

It’s definitely challenging to balance the various roles that I have. But I make a conscious effort to protect time for my family. My wife is a home-maker; she takes care of our children during the day.

My parents also help us out a lot.

That being said, I try to be more efficient in time management. It is definitely harder to set aside “me” (personal) time.

I try to find time to run in the mornings.

It is a good time for me to reflect.

As for my professional roles, I feel that teaching and treating are intertwined.

They are all part and parcel of being a doctor – as I treat patients, I find opportunities to teach our next generation of doctors. I had the privilege of having learnt from past mentors and tutors and I am doing likewise now.

10

Could you share some plans for NUHCS in the next 5 years?

The need to train excellent doctors who can treat future generations of patients is one of our key focuses. We have recently undertook a major review of existing teaching models and will be implementing a new one geared towards future doctors who wish to train in cardiology.

Hopefully through this, we will be able to enrich our students’ learning by providing them with structured and systemic training coupled with ground / bedside experience. This means to impart both the science (skills) and art of medicine – inculcating values of being a truly good doctor.

NUHCS also aims to be a leader in cardiovascular research. We have continued to compete for and secured several national and international grants to continue important research.

My interest is in bio-mechanical research and our team aims to develop new heart valve platforms to treat patients. I am also interested in the unique differences in Asian patients with heart valve disease. We have completed a local study on the epidemiology of patients with valve conditions and will be starting a study assessing the anatomical differences between Asian and Caucasian heart valve patients.

As we are seeing an increase in the number of complex diseases, NUHCS hopes to build up more collaborative treatment models unique to Singaporeans in the coming months. We want to develop hybrid therapies that can optimise patient outcomes.

Our entire NUHCS team of educators, clinicians and researchers are committed to keep Singaporeans in the best of cardiac health.

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UPCOMING

EVENTS

NUH GP CME Programme 2013 Please refer to our GPLC website for online registration.

July SATURDAY

06

Cardiac, Thoracic & Vascular (CTVS) Updates in Lung Cancer Management

SATURDAY Gastroenterology From Esophagus to Bowels The Bare Essentials

SATURDAY Cardiology Cardiology Update: Management of Common Cardiac Problems

MEDTECH & SURGICAL EXCELLENCE CONGRESS

31 Oct to 2 Nov 2013 NUHS Auditorium

13

20

Topics include: Impact of Technology in Surgery; Quality & Safety in Surgery; Surgery in ASEAN: From Humanity to SOUL; Evolution of Surgery Education; Multi-disciplinary Future of Surgery; Controversies in Surgery For more info, please visit http://surgery100.sg

Event information listed is correct at time of print.

While every attempt will be made to ensure that all events will take place as scheduled, the organisers reserve the rights to make appropriate changes should the need arises.

Please refer to our events calendar at www.nuh.com.sg/nuh_gplc for more updates and information.

A Publication of NUH GP Liaison Centre (GPLC) Advisors A/Prof Goh Lee Gan Editor Esther Lim Editorial Member Lisa Ang We will love to hear your feedback on MĂŠdico.

Please direct all feedback to: The Editor, MĂŠdico GP Liaison Centre, National University Hospital 1E Kent Ridge Road, NUHS Tower Block, Level 6, Singapore 119228 Tel: 6772 5079 Fax: 6777 8065 Email: gp@nuhs.edu.sg Website: www.nuh.com.sg/nuh_gplc Co. Reg. No. 198500843R The information in this publication is meant purely for educational purposes and may not be used as a substitute for medical diagnosis or treatment. You should seek the advice of your doctor or a qualified healthcare provider before starting any treatment, or, if you have any questions related to your health, physical fitness or medical condition(s).

Copyright (2013). National University Hospital All rights reserved. No part of this publication may be reproduced without permission in writing from National University Hospital.

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