Friday, 26 January 2007

Amiodarone and Cardiac Dysrhythmias

Today's Blog is based on my own experiences in the treatment of cardiac dysrhythmias with Amiodarone.

My being one of the few physicians in Japan who has had experience of the use of Amiodarone (in UK patients) I hope the following will provide you with some 'hands-on' information about this drug.

When I have talked of Amiodarone in Japan I am always met with the same answer and that is Japanese patients do not want to take Amiodarone because of its side effects.

However, from my own experience, in treating many hundreds of patients with intravenous and oral preparations of Amiodarone in the UK, I have always found it to be a safe drug to use and occasionally there is the patient with amiodarone-induced side effects, but its benefits frequently outweigh its risks.

Amiodarone is usually prescribed for atrial fibrillation, but it is also used in the treatment of flutter, WPW, VT and VF.

The side effect profile includes asymptomatic corneal deposits, skin photosensitivity, slate grey discoloration of the skin (rare and with chronic use), thyroid dysfunction, liver dysfunction, pulmonary alveolitis and fibrosis, long QT/Torsade de Pointes, amongst others. However, it is a bit like reading the side effects of almost any major drug-- not all patients get all side effects and most patients get none of the serious listed side effects.

I have seen the occasional patient with thyrotoxicosis, pulmonary fibrosis and skin changes, but they are the exception rather than the rule.

I have seen many patients very effectively treated with this drug including a family relative who had Woolf Parkinson White Syndrome.

The other treatments for AF such as beta blockers, calcium channel blockers e.g. verapamil, are still effective drugs although they are not true chemical cardiovertors but rate limiting agents and both these class of drugs can reduce cardiac muscle contractility and function, which Amiodarone does not appear to do. Other drugs such as flecainide or propafenone (Class 1c) can be used in the setting of Acute AF treatment but flecainide cannot be used in patients with underlying ischaemic heart disease, unlike amiodarone, and both drugs used long term may increase mortality. Some Class 1a agents can also be used, but if toxicity occurs there can be pro-arrhythmic effects.

In the UK, in a patient with fast AF without cardiovascular compromise, unless contraindicated, in my opinion, most physicians would tend to use IV amiodarone infusion to rapidly slow the AF with an aim to chemically cardiovert the rhythm and oral therapy would then be instituted. Of course most physicians have their own personal preferences and sometimes use other drugs instead. If that fails, they would consider DC cardioversion if AF had occurred within 48 hours.

Amiodarone is usually continued in patients who do not initially cardiovert with concomittant anti-coagulation, and after 4 weeks, if there are no contraindications such as cardiac thrombosis on echocardiography, they would be electrically cardioverted. Amiodarone in conjuction with electrical cardioversion improves the cardioversion rate and patients can stay in sinus rhythm for longer.

In the UK Resuscitiation Council Guidelines over the past several years, Amiodarone has been included as the main anti-arrythmic agents to be used in VT or VF treatment rather than lignocaine/lidocaine. I have personally treated VT with Amiodarone and cardioverted patients without the need of electrical cardioversion.

The use of amiodarone can also coarsen VF from a situation of 'fine' VF making the rhythm more treatable by defibrillation.

As I am informed, at the present time, Japan has only just licensed the oral formulation of amiodarone last year but IV is still not available.

However, now that oral amiodarone is available, you now have a very effective drug at hand for the treatment of the very common cardiac problem of AF. From my own experience, and from reading the literature, this drug is regarded as safe when used correctly, and at a minimum maintenance dose of 200mg/day there should be minimal side effects.

Bear in mind that Amiodarone has a very long half life as it is very liposoluble and even on stopping such medication, the literature suggests that it may continue working for up to a year.

Always refer to your Japanese drug guides for directions when considering prescribing any new drug

There are new agents that may be available in the next few years and these include purer Class III agents such as ibutilide, dofetilide and dronedarone, the latter being a deiodinated derivative of amiodarone which has no organ toxicity and a better side effect profile.

If you would like further information about my experiences with this drug then please write including your email.

Thursday, 25 January 2007


Poisoning from drugs or toxic substances is a vast topic and to cover this in a blog would be impossible.

When dealing with poisonings it is necessary to establish whether ingestion was accidental or deliberate.

In my experience, deliberate ingestion is usually done by people wanting to committ suicide and sometimes, unfortunately, they succeed despite medical intervention.

When investigating an ingestion, one needs to establish the drug/s or toxin/s ingested, their dose or quantity and the time at which these agents were taken e.g. at the same time or staggered over hours or days.

In the UK, most overdose patients use acetaminophen which effects can take up to 48-72 hours before signs of acute liver failure ensue. Sometimes aspirin is also ingested and some of such overdoses are done under the influence of alcohol, which can worsen matters due to the combined toxic effects of such ingestions.

Hence, it is quite usual and proper to examine blood for these above agents even if the patient denies taking them or as part of an overall drug screen in the intoxicated patient. Tricyclic agents can also be tested for, as can urinary amphetamines / cannabinoids.

It is of prime importance to check for the above agents as treatment is available to reverse the associated problems caused in the early stages of ingestion.

For example, acetaminophen ingestion can be treated with iv n-acetylcysteine or oral methionone to reduce hepatotoxicity and renal injury and forced alkaline diuresis for aspirin overdose respectively. Activated charcoal can bind the tricyclic antidepressant agents plus many other drugs which can be inactivated by this method.

One very real example I saw and eluded to yesterday in my blog was of a female patient of 30 years old that I saw in the UK who presented with an overdose of Ethylene Glycol (EG) and alcohol. She presented with a decreased conscious level and her family had found an empty bottle of the EG around her plus it was noted she had been drinking Gin.

On admission her vital signs were stable, but conscious level was GCS reduced with the patient not eye opening, confused words and withdrawal to pain (E1 V4 M4 =9/15), pupils were 4mm each but unreactive. Reflexes were generally absent except for the triceps bilaterally. Babinski sign was uninterpretable.

Chest and abdominal examinations were normal.

Blood gas showed a pH of 7.1, pCO2 14, HCO3 3.8, BE -25, pO2 98.

Anion Gap 26

BUN normal. Creatinine 1.2, Na 134, K 7.0

Corrected Calcium for Albumin = 8.6

Liver function Normal.

WCC 28.8 but other blood elements normal.

Urine analysis - normal. No blood / protein / casts

With the Anion Gap being > 25 and a profound acidosis with a very low HCO3 <8,> methanol or ethylene glycol. Hence the blood results fitted with the history. However, the severe side effects of these agents are blindness or renal failure respectively.

The patient was given rehydration and bicarbonate and therapy for hyperkalaemia (see blog of yesterday)

By morning, her GCS had improved and she was able to open her eyes on command, follow commands and answer questions appopriately (GCS 14/15).

On reviewing the patient, it appeared that left flank pain was a new problem and the renal failure was now becoming worse with a rising BUN and creatinine. The K had normalised to 3.5. Calcium was still with normal limits.

It was suggested that the patient be given the Alcohol Dehydrogenase Inhibitor Fomepizole or iv alcohol to slow down the break down of the ethylene glycol. The former drug has a much better treatment profile and is easier to control with few side effects rather than the undesired effects of alcohol.

Moreover, the patient was given mulitvitamins such as folate, Vit B1 and Vit B12.

The concern about this patients kidneys made me concerned about ensuing renal failure from the formation of Calcium oxolate and other byproducts, which is the by product of EG breakdown through binding of free calcium.

Hence, when a patient is admitted poisoning, history can be extremely helpful although with a semi-comatosed patient such history will need to be taken from family or friends. Inviting such bystanders in to obtain information can provide a wealth of information and such people will feel that they have been empowered by the medical team and feel respected, and they are less likely to complain about YOU for the fact that they have been kept appraised of the information.

Physical examination may not be very helpful in these cases.

However, basic blood tests including an ABG, drug levels of common poisonous drugs plus blood chemistry can point the physician in the right direction.

One of the best texts I have found to date is UpToDate ( which is a paid subscription service to the most up to date of medical information including poisonings.

I would highly recommend this service.

All the best!

Wednesday, 24 January 2007

Treatment of Hyperkalaemia

Both High potassium (hyperkalaemia) and Low potassium (hypokalaemia) levels can cause significant morbidity and mortality if left untreated.

Both problems have a wide number of causes, and treating the underlying problem will correct the disturbance once identified. Today, I will deal with hyperkalaemia.

Hyperkalaemia (K >5.0mmol/L)

Hyperkalaemia appears to become a problem for most patients when the level is >6.5mmol/L at which time the cardiomyocytes are most unstable and it is possible to develop life threatening dysrhythmias.

The typical ECG shows hyperacute T waves (Tall Tented T waves) and this should cause the doctor to act quickly-- this is a Medical Emergency. Other features include flat P-waves, increased PR interval. The QRS patten can eventually widen leading to a sinusoidal patterns and eventually VT/VF.

Causes of Hyperkalaemia

Dietary-- often forgotten! However, bananas, citrus fruits e.g. grapefruits, oranges have high levels of K. Salt substitutes, herb and nutritional preparations e.g. PEG feeds.

Drugs-- Lactulose (contains K), K supplements, ACEI / ARB / Aldosterone inhibitors can result in high K levels. Nephrotoxic drugs e.g. vancomycin, gentamicin can cause intrinsic renal dysfunction and the uraemia results in hyperkalaemia.

Other drugs known to raise K levels include:

Beta-blockers (reduced renin secretion and reduced cellular uptake of K), Heparin, Septrin / Bactrim (blocks apical membrane Na channels in distal nephron thereby inhibiting K secretion), Pentamidine, Penicillin G potassium, ketoconazole (impairs aldosterone metabolism, reduces aldosterone)

Aspirin overdose can result in a metabolic acidosis and hyperkalaemia. If an overdose of drugs is suspected and the patient has an acidosis, always check aspirin levels. In any case, aspirin lab levels should always be a routine tests in any overdose, including acetaminophen and tricyclic antidepressant levels.

Drinking de-icer Ethylene Glycol can also result in a metabolic acidosis and hyperkalaemia may result.

Infection- Sepsis resulting in renal injury from direct toxin effects to septicaemic shock can cause hyperkalaemia.

Endocrine-- Addison's disease ( low Na: High K), Diabetic Ketoacidosis, Hyperglycaemic Hyperosmotic Syndrome with renal failure can cause increased K.

Trauma-- Rhabdomyolysis from trauma, shock or infection results in release of large amounts of K which can result in cardiac arrest. Hypertonicity e.g. from a syndrome of hyperpyrexia related to anti-psychotic medication can result in rhabdomyolysis and raised K.

Haematological-- Haemolytic anaemia can result in intracellular release of K as can tumour lysis syndrome. Traumatic taking of blood can give a false reading of hyperkalaemia although most labs will report that the blood was haemolysed. Stored red blood cells release their K and hence, infusion of such cells might result in hyperkalaemia especially if the patient already has an underlying problem with raised K e.g. renal failure.

Metabolic-- metabolic acidosis of any cause can result in hyperkalaemia as a result of the competition for H/K release from the kidney into the urine. Hence, renal failure, hepatic failure, respiratory failure (type 2) and cardiac failure can all result in acidosis and hyperkalaemia.
Lactic acidosis from muscles hypoxia from hypoperfusion can result in raised K levels.

Type 4 Renal tubular acidosis (unresponsiveness to aldosterone) raises K levels too.

Familial Hyperkalaemic Paralysis and other rare genetic disorders.

Emergency Therapy

1) Calcium Gluconate 10ml 10% solution given over 2 mins- stabilises cardiac muscle cells

2) Glucose-Insulin infusion: 50ml of 50% glucose with 20 units of rapid insulin given to the patient over 1 hour

3) The above measures can be repeated if K level fails to decrease

4) Beta- stimulant drugs e.g. salbutamol, メプチン will cause a Temporary flux of K into cells thereby decreasing serum K levels. This can be given via a nebuliser in the ER department or on the ward

5) Furosemide (ラシクス) can sometimes be given provided that the cause is considered to respond to such therapy. However, it would be inappropriate to give such therapy if there is an element of dehydration as it would make that problem worse, whereas in fluid overload, it might be an appropriate therapy to use.

6) Ion Exchange Resins-- Calcium Resonium can be given orally or rectally and they will exchange one Ca ion for two K ions. They will cause a gradual decrease in K level over hours to days and so although they can be given during the emergency period, their effect will not be evident immediately. They can also cause constipation so make sure than a laxative is provided and not with Lactulose!!!

7) Infusion of bicarbonate-- can sometimes be considered but usually this is only given if the pH of the blood is very low e.g. pH<7.2, style="color: rgb(102, 51, 255);">8) Haemofiltration / Dialysis-- sometimes the patient will not respond to conservative less interventional therapies and so detoxifying the blood using haemofiltration / dialysis may be the only effective method for treating the high K levels. It is often best to speak to the nephrology services earlier rather than later so that preparations can be made to haemodialyse patients.

Clinical Gem: Insulin therapy is less likely to work if the patient is dehydrated or has a poor circulation as insulin needs blood to get to muscle!! Hence, always correct fluid balance status in your patients.

Assess fluid status by checking pulse, blood pressure, skin turgor, mucous membranes (is the tongue dry?), urine output (should be as a minimum 0.5ml/kg/hr; so in a 60 kg male = 30ml urine per hour) and consider CV line insertion and monitoring CV pressure.

Tuesday, 23 January 2007

Fever, Diarrhoea and Muscle Pain

This Case Has Been Anonymised to Safe Guard Patient Confidentiality

A 50 year old male patient who is a taxi driver who is normally fit and well who presented with a short 6 day history of:

1) Fever
2) Diarrhoea
3) Muscle pain
4) Dry cough

The fever was the initial symptom and was continuous rather than intermittent. The was no associated rigors (shivering) or sweats. The diarrhoea was non-painful, a dark colour but no visible blood or malaena (tarry stool).

The patient had been having diarrhoea once per day.

On the day prior to admission, he also had vomiting once although this became mixed with the diarrhoea so he was unable to describe the look of the vomitus.

The muscle pain was described more of a dyscomfort and was generalised. There was no associated joint pain or swelling and no skin rash. The cough was intermittent and dry. No sputum and no haemoptysis. No dyspnoea.

On further questioning, the patient had eaten sushi / sashimi one week ago ( one day before becoming unwell) but he could not remember what type of raw seafood as he had also been drinking alcohol on that day. He denied eating raw chicken or oysters. Being a taxi driver he usually bought an o-bento lunch box from the local convenience store and this was usually sushi.

He had no history of inflammatory bowel disease and no eye symptoms. He had never had any joint disease.

Previous medical history included 1) hypertension 2) renal glomerulosclerosis since a child and he took Olmesartan, Amlodipine and Allopurinol.

He otherwise drank alcohol occasionally and was an ex-smoker having at one time smoked 30 cigarettes per day.

On examination, he looked relatively well. Temp was 39 degrees C. No Cervical lymph nodes and no evidence of clubbing or splinter haemorrhages. Eyes showed conjunctival injection and mouth appeared appeared slightly red and the soft palate had white vesicular lesions that could not be scraped off. The tongue was coated and appeared to be candida albicans infection.

Blood pressure was 106/5o, pulse 72 bpm regular, JVP was not raised. There were no heaves or thrills and heart sounds 1 & 2 were present and there were no mumurs evident. Leg examination was normal with no oedema or DVT identified.

Respiratory rate was regular at 18/minute, normal percussion sounds and vesicular breath sounds. There was no wheeze or crepitations.

Abdominal examination revealed a soft, non-tender abdomen, with no evidence of hepatosplenomegally. There was no renal angle tenderness and bowel sounds were slightly increased. Rectal examination by the junior doctor revealed occult blood but there was no evidence of a mass and the examination was non-tender.

Skin was grossly normal.

Clinical Impression / differential diagnosis

Infective Diarrhoea

Bacterial diarrhoea e.g. Salmonella, E. coli, Shigella, Campylobacter, Yersinia enterocolitica, vibrio vulnificans, Clostridium difficile

Viral diarrhoea e.g. adenovirus (sore throat, red eyes, fever, diarrhoea-usually non-bloody)


Inflammatory Bowel Disease e.g. Ulcerative colitis or Crohn's disease (bloody diarrhoea / fever / eye signs)

Systemic Lupus Erythematosis (more a cause of abdominal pain than diarrhoea)
Polyarteritis nodosum

The Laboratory data revealed Hb 15.4 g/dl, low white cell count of 2.9, low platelets of 4.0, high fibrinogen level and normal INR/APTT. BUN was 26 and Creat 2.3 (normally 1.2), normal Na/K. Liver function was normal. CK normal. CRP was 9.

Blood smear showed no fragmented red cells. Stool examination revealed numerous white cells in the stool.

One concern was of a Haemolytic Uraemic Syndrome (HUS), but the history had been going on too long for this problem and the patient was well. Moreover, this clinical syndrome is predominantly seem in children. Another concern was DIC, but the blood smear was normal and the fibrinogen level was HIGH not low and one might see a MicroAngiopathic Haemoltic Anaemia (MAHA), raised INR and a low Haemoglobin is severe circumstances.

Another consideration was of Thrombotic Thrombocytopaenic Purpura (TTP) which is an adult problem associated with E. coli 0157:H7 infection just as is HUS, but there was no report of clumped platelets and the patient had no neuropsychiatric symtoms and no evidence of bleeding or haemolytic anaemia. TTP can also be found as a consequence of drug reactions particularly with Ticlopidine (which is used in Japan) where patients develop antibodies against the ADAMTS 13 protease that usually cleaves vonWillebrand Factor deactivating this enzyme. Familial cases of TTP show no activity of the above protease enzyme.

If this patient had an underlying immunodeficiency, for example AIDS, then other more innocuous infections could be a cause of bloody diarrhoea, fever, exudative sore throat and general systemic upset including: varicella zoster virus / Herpes Simplex Virus / Cytomegallovirus all of which can cause ulceration to the GI tract. Other immune deficient associated infections include the protozoal infections such as cryptosporidium, isospora belii although these do not cause a bloody diarrhoea.

In fact, the low white cells and platelets were likely related to a consumption from sepsis with the target of the sepsis being the bowel, which would explain the numerous white cells seen in the stool.

The patient was treated with intravenous antibiotics to cover the gram negative organisms and was rehydrated. By the next morning, the patient felt alot better and the diarrhoea and vomiting had stopped.

The patient had a colonoscopy to try and rule out inflammatory bowel disease.

The above example, however, shows you that fever, diarrhoea, cough, and myalgia do have a wide spectrum of possible diagnoses.

In view of his food history, which element is often left out of the medical history, it seems more than likely that he picked up a bacterial infection from contaminated food one week ago. In view of the relative bradycardia compared to his high temperature (which should have caused a higher pulse rate) and the dry cough and the invasive nature of this probable infection, this makes me consider invasive salmonella such as salmonella typhi or paratyphi as the cause of an Enteric Fever.

What is your opinion?? Please let me know.....

Monday, 22 January 2007

Great Case- Physical Examination of Heart Failure

This case has been anonymised to safe guard patient confidentiality.

This case is a typical General Internal Medicine (GIM) case, but it is important to get it correct.

The following case shows how a case should be written in the patient notes in the form of how to show pertinent positive and negative findings for each of the three main systems. The clinical diagnosis (assessment) and the plan for each problem is identified. Only by doing this can a logical way of dealing with complex and multiple problems be made easier to deal with, which improves on patient care and makes the problems easier to understand.

This patient was admitted with dyspnoea that gradually worsened over the day prior to her admission. The dyspnoea prevented her from lying flat and she was then admitted to hospital by ambulance. She apparently had no other symptoms.

She had a previous medical history including:

Acute MI x 3
Repeated admissions for Congestive Heart Failure (CHF)
Coronary artery stenting x2 last year
Chronic Renal Failure secondary to AMI last year

No Hx of diabetes.

Medications include 1) furosemide 20mg OD 2) aspirin 3) Amlodipine 10mg OD

She still continued to smoke 30 cigarettes per day and had done so for the last 70 years!
She drinks little or no alcohol.

On direct questioning, she denied any recent chest pain, no cough, sputum, haemoptysis or fever. She had chest pain during her last AMI but has had no recurrence on this admission or in the period before admission. Recently she had been thirsty and has produced darker coloured stool on defecation but she denied any constipation.

On examination, she looked well and was smiling.

BP 155/66 (wide pulse pressure), HR 90min regular, RR 30/min, Sats 86% on room air (94% on 5L oxygen), Afebrile (normal temperature)

No Jaundice. Anaemia- pale conjuctivae, No Clubbing, Cyanosis positive. Tar stained nails from cigarettes.

CV Examination: Waterhammer Pulse (Right Brachial pulse- high pressure felt under pulps of examiners fingers then collapses whilst arm elevated in the air), Quinke's sign Negative, Corrigan's Sign Positive (visible pulsations of carotid due to high output from heart), JVP raised about 6cm H2O. Apex not felt and no heave or thrills. Heart sounds 1 & 2 present and diastolic mumur at apex only with loudening on expiration. No radiation to left axilla. Patient unable to be sat forwards. Leg oedema present to 2/3 up both lower legs. No evidence of DVT.

Respiratory Examination: Tracheal Tug but central (reduced space between suprasternal notch and laryngeal cartilage consistent with chronic lung disease), percussion was dull at both lateral chest walls and at both bases of the lungs consistent with bilateral pleural effusions. 'Wet' crackles present 2/3 the way up both lungs. No wheeze. No Lymph nodes palpable.

Abdominal Examination: Soft, non-tender, semi-hard, smooth mass about 20cm x 20cm arising from the pelvis, but the examinaing hand could get below it and above the pelvic brim. Dull to percussion. Reduced bowel sounds over area of mass, but bowel sounds were present. No pelvic lymph nodes palpable. No hepatosplenomegally. Rectal examination was excluded due to difficulty lying patient on lateral side.

Basic Lab Data

Lab data showed anaemia of Hb 8.5 g/dl, MCV 104, BUN 35 Creat 2.36, normal Liver tests, BS 300, HbA1c 6.2%, CRP normal, WCC 14.4, Lymphocyte % raised 54%. LDH normal range. Troponin T Positive (between 0.06 and 0.1-- minor myocardial damage), CK normal.

ABG (on admission): pH 6.9, HCO3 14.1, PCO2 69, PO2 60, BE -12

Clinical Diagnosis based on History and Physical (plus some Lab data observations)

1) Heart Failure worsened- causes
i) Possible new MI
ii) Under medicated for heart failure (not on ACE-I / ARB)
iii) Hypothyroidism (raised MCV, anaemia)
iv) Systolic dysfunction due to metabolic acidosis
v) Worsening failure due to anaemia (high output HF)
vi) Worsening Aoartic Regurgitation
vii) Worsening failure due to Meig's Syndrome from Ovarian tumour

2) Aortic Regurgitation

3) Tricuspid Regurgitation

4) Abdominal Mass
i) Possible Benign Ovarian tumour
ii) Possible Malignant Ovarian / Bowel Tumour

5) Anaemia (with raised MCV)
i) Possible folate / B12 deficiency due to enlarging cancer
ii) Hypothyroidism
iii) Bleeding (imature reticulocytes enter blood stream)
iv) Bone Marrow invasion from tumour (immature blood cells enter blood stream})

6) Type 2 Diabetes Mellitus ( patient had 3 three random BS > 200mg/l and HbA1c 6.2%)

7) Mixed Metabolic and Respiratory Acidosis
i) From combination of Renal failure (metabolic component) and Heart Failure (respiratory acidosis and hypoxaemia)
ii) Diabetic Ketoacidosis (ketone bodies -- metabolic acidosis) and Heart failure (respiratory acisois)
iii) Lactic Acidosis from possible recent AMI plus heart failure

CXR revealed small bilateral effusions and upper lobe diversion and fluid in the right horizontal fissure. The LA shadow appeared enlarged. All features consistent with CHF.

ECG showed Left Bundle Branch Block-- consistent with previous MI (ECG normal prior to last MI)

Urine Analysis: Ketones Negative

Serum Lactate: Negative

CT was performed and revealed a large cystic mass arising from the pelvis. Awaiting formal diagnosis by the gynaecologists, but possible ovarian tumour.

Hence, in this case, the history and physical provide the physician with most of the answers. Careful cardiac examination showed not only probable ventricular dysfunction but also AR and TR just by looking at the neck and identifying carotid pulsations and the JVP. Waterhammer pulse and the diastolic murmur convinced me of the valvular problem.

The diabetes could be treated for symptomatic purposes to prevent thirst and polyuria rather than aiming to obtain perfect control. Metformin is contraindicated due to risks of lactic acidosis as a result of renal failure. The glitazones (e.g. rosiglitazone and pioglitazone) are contraindicated as CHF can worsen due to fluid retention effects from these drugs. The best oral medication in these circumstances would be a short acting sulphonulyurea such as Gliclazide. The renal failure prolongs the serum half life of SUs and the effects are for longer and hence, a short acting agent would be preferable. Glibenclamide and glimepiride would be dangerous and cause hypoglycaemia due to their long time of activity.

If this patient had had typical ischaemic chest pain and a troponin rise consistent with an AMI which could have been exactly calculated when it occurred, then IV insulin should be given consistent with the DIGAMI study (Diabetes and Insulin Glucose in Acute Myocardial Infarction), which study showed that tight glycaemic control improves mortality in the peri-AMI setting. Following this, the DIGAMI 2 study showed that there was no difference between using insulin or oral hypoglycaemic agents long term so long as tight control was maintained.

Should the aspirin have been stopped?? Well, there was no evidence of haemorrhage. The aspirin providing benefit for the patient's cardiac risks and new diagnosis of DM may still out weigh the risks. However, the patient has NHYA Stage IV heart failure and a malignancy which gives her a poor prognosis and hence, would it have been right to continue such treatment which might cause heamorrhage? Only further tests and observing the patient would provide the answers.

The heart failure was treated with 1) IV nitrates 2) Furosemide 60mg and this produced a marked diuresis and over the night of her admission, the patient's clinical condition and ABG improved.

CHF treatment

1) Fluid restricted to 500ml / day orally
2) Low salt / No added salt diet
3) Daily weighing of the patient to have exact measure of fluid loss
4) IV furosemide until fluid status is corrected and then increase the stable daily oral furosemide dose to 40mg/day OD
5) Consider adding in an ACE-I (which improves cardiac function and reduces hospital admissions from CHF and is also reno-protective in DM; hence dual beneficial functions but watch for worsening renal function. A 30% increase in creatinine is acceptable when starting ACE but if higher and / or K+>5.0mmol/L then consider stopping such therapy)

Anaemia and Raised MCV

6) Obtain thyroid studies, iron studies, folate, B12, blood smear

Cardiac Function Investigation

7) Order Echo to see current cardiac function and valve status

Investigation of possible Ovarian / Bowel tumour

8) Tumour markers esp CA-125 (raised with ovarian tumours), CEA

Diabetes Mellitus

9) Consider low dose Gliclazide / Insulin

As can be seen, this case is quite complex but it can and has been broken down in to smaller manageble pieces and there is a plan for every problem.