METHODS

In November 2000 the principal author (JRB) undertook a research visit to Uppsala and Dalarna Counties, Sweden. This included visits to Uppsala City hospital and dispatch centre, ambulance stations in several counties of Sweden and also to Dalarna County, which has one of the longest experiences of prehospital thrombolysis in the world.

Meetings were held with paramedics and doctors involved in prehospital thrombolysis, including the medical directors of two ambulance services and a consultant cardiologist. Results from local audit in Dalarna County were also collected and statistically analysed using χ² testing. A p value of less than 0.05 was taken as indicating statistical significance.

Stages in successful implementation, and potential barriers to change, were identified in order to construct a template for application to UK practice.

RESULTS

Background

There are about 75 hospitals in Sweden. Nearly all of these have an established system of prehospital ECG transmission, while approximately 50 have some form of prehospital thrombolysis.

The Swedish Board of Health and Welfare approved paramedic thrombolysis in 1999. This decision was based, in part, on pilot studies undertaken in Dalarna County, which has been researching prehospital thrombolysis by paramedics since 1997. A standardised, and nationally approved, training programme was drawn up consisting of an extra two days in the paramedic training programme plus a one day refresher course every year incorporating a practical rehearsal in which medical students act as “patients”.

Many different thrombolytic drugs have been used in Sweden, including streptokinase, tissue plasminogen activator (TPA), and reteplase. Currently reteplase is used almost universally. This is given as two bolus doses of 10 units, 30 minutes apart. Further benefits are anticipated from the introduction of single bolus thrombolytics. At present Swedish paramedics only administer thrombolysis on the authorisation of a doctor after electronic transmission of the ECG. Different regions of the country use different ECG transmission methods, according to local preference. These vary from modified defibrillators/monitors to integrated electronic patient records and dedicated data transmission devices.

General observations from Sweden

Paramedics

• Normal practice is to move the patient into the ambulance to perform and transmit an ECG as the necessary equipment is usually heavy and bulky to carry. This increases the on scene time by around three minutes.

• There was a great deal of trepidation when prehospital thrombolysis was given by each paramedic for the first time, but they quickly became a lot more relaxed once a few patients had been successfully treated.

• In Mora, paramedics are encouraged to give thrombolysis in the ambulance even if they have just arrived at the hospital. This is to avoid the inevitable “door to needle” time that will occur if the patient is unloaded before receiving thrombolysis.

Doctors

• On the whole Swedish cardiologists are happy with prehospital thrombolysis because heart muscle is being saved.

• There are no concerns regarding prehospital complications: bleeding problems (such a stroke or gastrointestinal haemorrhage) are not encountered in the ambulance, only in hospital afterwards. This view is supported by data collected from Dalarna County (see below).

• Prehospital thrombolysis is found to be more effective when a senior doctor is available to respond to the transmitted ECG: junior staff often lack the confidence to authorise drug administration.

Service delivery

• Initially only very clear cut AMIs were thrombolysed in order to boost confidence in the overall system.

• While it was originally envisaged that prehospital thrombolysis would only be used in rural regions, it is now being administered anywhere, including urban areas. In the city of Uppsala all emergency ambulance calls are reached in five minutes. On scene time averages around 20 minutes, with a five minute journey time to hospital. However, as it requires only two to three minutes to obtain and transmit an ECG, and two to three minutes to give the drug, urban prehospital thrombolysis has been found to be nearly always beneficial.

• In some cases patients are not thrombolysed prehospital, but after ECG transmission are taken, on medical direction, directly to a cardiac catheterisation facility for emergency coronary angioplasty (PTCA). This strategy is most useful in urban areas where the patient is close to a 24 hour catheterisation facility, and where patient characteristics make urgent angioplasty the treatment of choice. If, however, the patient is a long way from a catheterisation facility then thrombolysis may be given first, followed by urgent PTCA if there is evidence of ongoing coronary artery occlusion.

• The most important factor has been to ensure that all parties have continuous education and support. In Uppsala this has led to a general upswing in prehospital thrombolysis, with increasing confidence and activity.

• The adoption of prehospital thrombolysis has increased awareness and led to widespread improvements in the whole chain of thrombolysis, even for those who come to the hospital without calling an ambulance.

Data from Dalarna County

A comprehensive audit of prehospital thrombolysis in Dalarna County has recently been undertaken. During 1998 thrombolysis was administered to 109 patients in the county who called an ambulance as a result of their symptoms. The location of thrombolysis is recorded in table 1. GP thrombolysis (11 patients) was carried out in only one region of Dalarna County, perhaps reflecting a local interest, whereas prehospital and inhospital thrombolysis were more evenly distributed. Only one region, Avesta, did not undertake prehospital thrombolysis in the period studied. Of the 66 patients thrombolysed in hospital, 45 (68%) were male with a mean age of 68 years (range 43 to 88 years). The median duration of each component of the “pain to needle” time for inhospital thrombolysis is recorded in table 2. By comparison, the median time intervals for the 32 patients thrombolysed prehospital by paramedics using reteplase are recorded in table 3. In this group 23 patients (72%) were male, and the mean age was 62 years (range 41 to 79 years). It is clear that prehospital thrombolysis resulted in a considerably reduced “pain to needle” time, even though the average “pain to call” time was longer in the group thrombolysed prehospital. The median response time was the same in both groups, with the on scene time for those patients thrombolysed inhospital being very similar to the time between ambulance arrival and ECG transmission for the patients thrombolysed prehospital. Similarly, the median transport time to the emergency department for patients thrombolysed inhospital was almost identical to the time between ECG transmission and the actual delivery of thrombolysis for patients thrombolysed prehospital.

Interestingly, it was found that the introduction of prehospital thrombolysis reduced the “pain to needle” time for all patients, even those who conveyed themselves to hospital. This was attributed to a heightened awareness of the benefits of early thrombolysis.

Complications were also assessed during the study period. Prehospital complications for those patients receiving prehospital thrombolysis and those simply transported to hospital to receive inpatient thrombolysis are compared in figure 1, while inhospital complications for the two groups are compared in figure 2. Complications in the prehospital phase were found to be identical (25% for the prehospital group versus 24% for the inhospital group) while complications during the inhospital phase of care were doubled (from 25% to 50%) in those patients not receiving thrombolysis until they reached hospital (p=0.018 on χ² testing). When all prehospital and inhospital complications are combined the benefit of prehospital thrombolysis remains (p=0.018). Six per cent of the patients receiving prehospital thrombolysis died while in hospital compared with 12% in the group receiving inhospital thrombolysis, though this difference does not achieve statistical significance (p=0.36), perhaps because of the small number of patients involved.

There does seem to be an increased risk of ventricular fibrillation or ventricular tachycardia in those patients thrombolysed prehospital (19% versus 9%), but this also does not reach statistical significance (p=0.17) and is a complication that paramedics in both Sweden and the UK are very experienced in dealing with, as evidenced by the fact that there were no prehospital deaths.

DISCUSSION

Prehospital thrombolysis has clearly proved successful in Sweden, but there remains a paucity of hard scientific data that can be readily applied to the UK. Sweden is a much larger country with a smaller population, so ambulance journey times are often longer than in the UK. Furthermore, the specialty of emergency medicine is not recognised in Sweden, so that inhospital thrombolysis will usually only be given on a coronary care unit (CCU). This is analogous to the situation in the UK 10 years ago, when patients arriving in the emergency department (ED) were often transferred to the CCU for thrombolysis, causing significant further delays. Improvements in the UK system mean that many patients presenting to an ED with AMI will now be thrombolysed promptly in the ED, with the potential to reduce the “door to needle” time to as little as 20–40 minutes.¹⁵ Nevertheless, patients thrombolysed in hospital will inevitably have a “door to needle” time that is unlikely to be decreased further: this is the primary rationale for carrying thrombolysis into the prehospital environment.

The information that is available from Dalarna County clearly supports prehospital thrombolysis. Median “pain to needle” time was reduced by 45 minutes, with the “call to needle” time falling from 98 to 43 minutes, an improvement of nearly one hour per patient. This time saving is very similar to the “door to needle” time, as a patient receiving inhospital thrombolysis will just be entering the hospital at the point where prehospital thrombolysis could have been administered. If the time between ECG transmission and the delivery of prehospital thrombolysis is used for patient transport then the additional delay in reaching the hospital will be minimal, and the patient will be close to the expertise of the receiving unit when the drug is actually delivered.

There is no evidence that prehospital thrombolysis leads to an increased incidence of complications: quite the reverse in fact. The prehospital complication rate was similar for the two groups, but the inhospital and overall complication rates were much higher for those patients who received inhospital thrombolysis, mainly because of an increased incidence of arrhythmias.

Nevertheless, these results must be viewed with caution as they arise from a process of simple observation and are therefore open to many possible biases. In particular, there is no randomisation, and it may be that the patients thrombolysed prehospital had more straightforward AMIs than those receiving inhospital thrombolysis. The sex distribution was similar between the two groups, but those patients receiving prehospital thrombolysis were, on average, six years younger, and this may have influenced the subsequent outcome. In addition, patients with heart conduction defects such as left bundle branch block are harder to diagnose,¹⁶ and are therefore less likely to receive prehospital thrombolysis, but have a worse prognosis than patients presenting without such conduction defects.¹⁷

The population of AMI patients and their presentation may be significantly different between Sweden and the UK. For example, in Sweden up to 50% of patients with AMI will transport themselves to hospital, rather than calling an ambulance or their GP. Another major factor may be differences in the “pain to call” time, which is consistently found to be the longest stage in the total “pain to needle” time.¹⁸ In this study the median pain to call time was 12 minutes longer in the group thrombolysed prehospital, but the significance of this is uncertain.

Stages in successful implementation, and potential barriers to change, are summarised in table 4. Aufderheide and colleagues from North America also discuss several of these issues further in a report published in 1996.¹⁹

While prehospital thrombolysis has proved successful in Sweden this cannot be automatically extrapolated to the UK. The two countries have different demographics and different healthcare systems. In remote regions prehospital thrombolysis will almost certainly be of benefit, as demonstrated in the GREAT study,⁵ and successful administration by general practitioners in such locations is an established fact in both countries. However, the vast majority of AMI in the UK occurs in urban and suburban areas where transport times are comparatively short and the potential benefits of prehospital thrombolysis are untested. The Swedish experience in Uppsala suggests that the introduction of prehospital thrombolysis may well prove beneficial even in larger cities, or if the drug is given at or close to hospital arrival, simply because the “door to needle” time is avoided, but research is urgently needed in this area. Patients suitable for emergency PTCA may also be identified and “fast tracked” to an emergency cardiac catheterisation facility, though few hospitals currently provide this service in the UK.

More than anything else there remains a need for robust research into prehospital thrombolysis as applied to the UK. The cost of implementing the sort of nationwide programme described in the recent “NHS Plan” would be considerable,²⁰ and must be balanced against alternative approaches such as better education of the public to reduce the “pain to call” time. It also seems likely that a transit time beneath which prehospital thrombolysis is no longer beneficial could be accurately identified, but a lack of research evidence significantly hampers the introduction of this important new development. In the meantime, implementation in the UK is likely to be heavily influenced by the recommendations of the European Resuscitation Council. These suggest that prehospital thrombolysis should be undertaken if the combined journey time and inhospital delay is more than 60 minutes, or if the journey time is 30 minutes or more.²¹ This is further developed by the National Service Framework for coronary heart disease, which states that prehospital thrombolysis is appropriate if the “call to door” time is likely to exceed 30 minutes.⁴

CONCLUSION

If the outcome of AMI in the UK is to be improved, and National Service Framework targets met, then prehospital thrombolysis is an important and promising development. Successful implementation in Sweden, demonstrating an effective service with considerably reduced “pain to needle” times, a statistically significant decrease in the rate of complications, and a real likelihood of substantial mortality benefit, offers important and valuable lessons for the UK. Several technical solutions already exist, and a single bolus thrombolytic agent is now available, but the main barriers to widespread implementation are related to the establishment of an effective training programme and the organisational changes that will facilitate this new practice. High quality research is urgently needed to guide the implementation of prehospital thrombolysis in a clinically and cost effective way, but ultimately it seems quite possible that a high proportion of the patients suffering AMI in the UK each year will be able to benefit from the mortality and morbidity gains associated with earlier thrombolysis.