Accident and Emergency Medicine, Ninewells Hospital, Dundee


Chest pain and thrombolysis

Euan Macgregor

Chest pain is a common presenting complaint of patients arriving at the Accident  and Emergency department. There are many differential diagnoses to consider and as usual, it is the clinical history that aids most in deciding how best to manage the patient.


There are many sources of chest pain including cardiac, respiratory, gastrointestinal and the musculoskeletal system.  Some of these can be extremely serious and life threatening. Often in the emergency department one must think in terms of the most serious condition that a patient can have and rule this out, rather than the usual method of thinking about the most common conditions first.  There are occasions when a unifying diagnosis can not be found.


When taking a history from a patient complaining of chest pain there are many questions to be asked. The severity, the site (including any radiation) and nature of the pain must be elucidated.  Also the mode of onset and any aggravating or relieving factors must be enquired about. Has the patient been admitted previously with a similar problem and you must specifically ask if they have angina and whether they have had a myocardial infarction in the past. Obviously there are many more questions to be asked of the patient but these will depend on the patient’s history of the presenting complaint.


Patients, their relatives and sometimes their GP’s primary concern is that the patient is having a myocardial infarction because coronary heart disease (CHD) is very common, particularly here in Scotland. CHD is the cause of much morbidity and mortality.  More than a quarter of a million people in the UK suffer an acute MI each year and it is the cause of some 125,000 deaths annually.1 An MI is a hugely significant life event, around 50% of patients will die within 30 days of the event and up to one third of those patients who do not survive, will die within the first hour after the onset of an MI.1 More than a half of all the patients that die due to an MI will die before reaching hospital or some other form of medical help.1


There are many risk factors implicated in the causation of coronary heart  disease. These can be thought of in terms of non-modifiable and modifiable risk factors. The non-modifiable risk factors include age, being male and a positive family history of ischaemic heart disease. The modifiable risk factors include smoking, diabetes, hypercholesterolaemia and hypertension. These are modifiable as if these conditions are treated well or the patient stops smoking then the likelihood of the patient suffering an ischaemic event can be lessened.


The characteristic symptoms suggestive of an MI would include severe, central, crushing chest pain which is not of sudden onset. It tends to come on while the patient is at rest and builds gradually rather than starting abruptly. The pain commonly radiates to the jaw or to the arms. Often the patient will be sweaty and will feel nauseous. They can be short of breath and will often think that they are dying. The pain will persist until the patient receives analgesia with diamorphine.


When assessing the patient one should always follow the ABC guidelines.  The patient should be closely monitored and a 12-lead ECG should be performed immediately. If the patient is stable then they should be given high flow Oxygen and an aspirin to chew on. A buccal GTN tablet should be given to the patient to put between their gum and their cheek. IV access should be gained and routine bloods should be taken off and analgesia and an anti-emetic given as soon as possible. It is handy to remember the mnemonic MONA in the treatment of a patient with an MI, this stands for Morphine, Oxygen, Nitrates and Aspirin.


To diagnose a myocardial infarction, three criteria must be met: first, the patient must have chest pain of a cardiac nature for a duration of less than 12 hours. Secondly there must be evidence of acute ECG changes in keeping with the diagnosis of an MI. Finally there must be a rise and then a subsequent fall in cardiac enzymes


There are two indications for initiating thrombolysis in a patient with cardiac chest pain. One is the presence of ST elevation of at least 1mm in the limb leads or 2mm in the chest leads on the ECG and the second is new onset of left bundle branch block (LBBB.) There must also be no compelling contraindications to thrombolysis. When meeting a patient for the first time it can be difficult to establish whether the onset of LBBB is new, without a previous ECG, this must be particularly difficult in the pre-hospital setting. Thrombolytic drugs are not without risk and careful questioning must be carried out to ensure that they are given appropriately.



ECG showing LBBB

The cause of an MI is usually a ruptured plaque or thrombus causing blockage of a coronary artery. This causes ischaemia of the myocardium and can cause death of heart muscle if prolonged. Thrombolysis has been shown to lead to coronary reperfusion in 50-70% of patients compared with a spontaneous rate of 20-30%. Streptokinase is the most commonly used thrombolytic agent because it is cheaper than the other available agents and clinical trials have shown that the efficacy of each of the agents is much the same.1 Patients can only receive Streptokinase once as it promotes an immune response and antibodies are produced against it. Subsequent administration would be ineffective and patients are therefore given an alternative, usually alteplase.


Patients must be rapidly examined because the initiation of treatment, after ruling out life-threatening conditions, is the priority. The examination should be focused on ruling out hypotension, listening for the presence of murmurs and identifying and treating pulmonary oedema. The presence of hypotension and left ventricular failure, amongst other factors, at the time of presentation are associated with a poor prognosis.


ST elevation occurs within minutes of the onset of a myocardial infarction and can remain for up to two weeks. The next ECG sign to evolve is usually T wave inversion. This can occur immediately and usually remains after the ST elevation has resolved. Pathological Q waves are the final sign to develop and these occur within hours or days and can persist indefinitely.


ECG showing an acute anterior myocardial infarction


There are a number of contra-indications to thrombolysis, the following table of questions is taken from a paper produced by David Pedley, specialist registrar in accident and emergency here at Ninewells. This is the questionnaire that the paramedics would follow and if the response to each question was positive in the context of a patient with an ECG confirmed MI, then the patient would receive thrombolysis.


Criteria that have to be met before thrombolysis can be initiated

A positive response is required to each question before thrombolysis is undertaken.

(a) Is the patient conscious and oriented for time, place, and person?

(b) Has the patient had typical symptoms of a myocardial infarction?

(c) Did the pain build up gradually rather than starting abruptly?

(d) Did the continuous symptoms start less than six hours ago?

(e) Can you confirm that breathing does not influence the severity of the pain?

(f) Is the patient unlikely to be pregnant?

(g) Can you confirm the patient has not had a miscarriage or given birth in the past two weeks?

(h) If the patient has ever suffered from a peptic ulcer, can you confirm that he or she has been free of symptoms for the past six months?

(i) Has the patient been free from any major neurological problems such as stroke, head injury requiring hospital admission, spinal operations, brain cancer, or aneurysms?

(j) Is the patient free from any bleeding tendency or recent (less than two weeks) blood loss (other than menstruation)?

(k) Can you confirm that the patient is not taking warfarin?

(l) Can you confirm the patient has remained free from any trauma in the past two weeks, or any major surgical procedure in the past two months?

(m) Can you confirm that the patient's blood pressure is less than 180/120 (either value)?






















The following table collates the available information on each of the thrombolytic agents currently used in treating patients with a myocardial infarction. It can be seen that the methods of delivery vary slightly between the different agents but the cost varies a great deal between the least expensive and the most expensive.




Route of Administration


(% of thrombolytic use)


(per patient Rx)


Up to 12/24 after onset of symptoms

IV infusion

53 – 83

£80 – 90 


Up to 12/24 after onset of symptoms

IV infusion or bolus injection

23 – 32



Up to 12/24 after onset of symptoms

2 IV bolus injections

12 – 15



Up to 6/24 after onset of symptoms

Single IV bolus injection


£700 - £770









Data taken from Prescriber Guide 2

Streptokinase appears to be an extremely cost-effective agent and randomised clinical trials have shown that there is no significant difference in terms of efficacy  between the thrombolytic agents.1 Streptokinase appears to be associated with a higher rate of allergic reactions and major bleeds requiring transfusions than the newer thrombolytics but the newer thrombolytics are associated with an increased risk of haemorrhagic stroke.1 These are the only major differences between the thrombolytics and thus the decision about which one to use must be based on clinical grounds and cost-effectiveness.


Dr David Pedley, a specialist registrar in accident and emergency medicine here at Ninewells conducted a study looking in to the viability of a system of prehospital thrombolysis, delivered by the paramedics.3 Their study used a mobimed system that allowed ECG’s to be transmitted using mobile phone technology to a base in the A&E department. There it would be inspected and if the ECG met the criteria for thrombolysis and the patient had no contra-indications then the paramedics would be instructed to give the patient thrombolysis with a bolus injection of tenecteplase. The National Service Framework for Coronary Heart Disease has set out a target time of 60 minutes from the when help is called to the time that the patient receives thrombolysis, the so called “call to needle time.” The results showed that the median call to needle time for patients treated prior to hospital arrival was 52 minutes whereas the patients who were treated in hospital from rural areas had a median time of 125 minutes. Patients from more urban areas had a median call to needle time of 80 minutes. This paper has shown that with proper training and the support of experienced members of staff in A&E, a system of prehospital thrombolysis for patients having an MI can be successful and safe.


There has been much research carried out into the most effective treatments to improve outcome after an acute myocardial infarction. These have compared Percutaneous Transluminal Coronary Angioplasty (PTCA) and thrombolysis. Clinical Evidence 4 found one systematic review and 23 Randomised Controlled Trials (RCT) showing that PTCA significantly reduced the combined end points of death, non-fatal re-infarction and stroke at 4-6 weeks compared with thrombolysis. In the longer term, over 6-18 months the outcomes were also better in those patients treated with PTCA than with thrombolysis. The review found that emergent hospital transfer for PTCA significantly reduced the combined outcome compared with on-site thrombolysis. PTCA reduced the risk of stroke compared with thrombolysis but increased the risk of major bleeding at 4-6 weeks. Much of these studies were performed in the United States and the facilities available at many hospitals there are much superior than here due to the differences in health care funding. Performing emergent PTCA is not yet part of the standard package of care given to patients with an acute MI in the UK. Here the emphasis is on early thrombolysis as we do not have the resources or staffing to provide such a service as could be found in specialist centres in the States. PTCA may well be held as an option for those patients where thrombolysis is contra-indicated






1.         Boland A, Dundar Y, Bagust A, Haycox A. Hill R, Mujica Mota R, Walley T, Dickson R. Early thrombolysis for the treatment of acute myocardial infarction: a systematic review and economic evaluation. Health Technology Assessment 2003; Vol.7: No.15


2.         Prescriber Guide – Summary of NICE guidelines for the early treatment of acute myocardial infarction.


3.         Pedley DK, Bissett K, Connolly EM et al. Prospective observational cohort study of time saved by prehospital thrombolysis for ST elevation myocardial infarction delivered by paramedics. BMJ 2003; 327: 22-26


4.         Clinical Evidence – Which treatments improve outcomes in acute myocardial infarction? BMJ Publishing Group Ltd 2003


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Last updated: April 10, 2004.