10 &12~t~n -Vaccination a prospect for the futureA commercially available H. pylori vaccine is prob­

ably still about 5 years away, but if successful , it couldboth prevent colonisation of H. pylori in non-infectedpeople and eradicate the organism in tho se who are in­fected.l''l A phase I study of an H. pylori vaccine hasshown it to be well tolerated.l'il

ReferencesI. NIH Consensus Development Panel on Helicobacter pylori in Peptic

Ulcer Disease. Helicobacter pylori in peptic ulcer disease. lAMA1994 lui 6; 272(1) : 65-9

2. Soil AD, on behalf of the Practice Parameters Committee of the .American College of Gastroenterology. Medical treatment of pepnculcer disease. Practice guidelines. lAMA 1996 Feb 28; 275(8): 622-9

3. Phull PS, Ryder SD, Halliday D, et al. The economi.c a~d .quality-o f-life benefits of Helicobacter pylon eradication In

chroni c duodenal ulcer disease - a community-based study.Postgrad Med 1 1995 lui ; 71: 413-8

4. Cottrill MRB. The prevalence of Helicobacter pylori infection in patientsreceiving long-term Hz-receptor antagonists in general practice: clinicaland financialconsequences of eradication using omeprazole plusamoxycillin or triple therapy. Br 1Med Econ 1994; 7: 35-41

5. Feldm an M. The acid test. Making c1inical' sense of the consensusconference on Helicobacter pylori . lAMA 1994 lui 6; 272(1) : 70-1

6. Rauws EAl , van der Hulst RWM. Current guidelines for theeradication of Helicobacter pylori in peptic ulcer disease. Drugs1995; 50(6) : 984-90

7. Penston lG. Review article: Helicobacter pylori eradication­understandable caut ion but no excuse for inertia . AlimentPharm acol Ther 1994; 8: 369-89

8. Schwarz T. Helicobacter pylori research news. Inpharma 1995 Oct14; (1008) : 11-2

When should general practitioners administer thrombolytics?General practitioners (GPs) can save lives by adminis­

tering thrornbolytics" to patients with suspected acutemyocardial infarction (Ml) if the journey time to hospitalis >30 minutes, or the combined journey time and hospi­tal delay is expected to be >60 minutes) I]

Because GPs may only see a few patients per yearwho could potentially require thrombolytic therapy, it isimportant that they receive appropriate training and for­mulate guidelines to follow.I-i

Early management of patients with MIEvery GP practice should have a clear policy for

managing patients with suspected acute ML This policyshould take into account:

• the distance to, facilities offered by, and audited'door-to-treatment' times of local hospitals

• availability of ambulances, and whether these carryresuscitation equipment and trained paramedics.I-l

The policy should include patient education, particu­larly for tho se patients with known ischaemic heart di s­ease, and full instructions for the ancillary practice staff.Ideally, guidelines should produced with the assistanceof the local cardiologist and health authority) I]

Tile decision to include a policy of GPadministration of thrombolytic therapyshould be gllidedlJy how milch earlierthrombolqtics could be administered

compared with the altematives. l l ]

Vol. 7, No.8; April 29, 1996

Time is of the essenceThe British Heart Foundation working group has rec­

ommended that patients with acute MI should receivethrombolysis, when appropriate, within 90 minutes ofalerting the medical or ambulance service.l- l

Depending on local circumstances, achieving thisstandard may involve direct admissions to coronary careunits, ' fast track' assessments in general accident andemergency departments, or prehospital administration ofthrombolytics by GPs.l2]

Guidelines forGP thrombolytic administrationGuidelines for GP administration of thrombolytic ther­

apy developed by the Clinical Resource and Audit Group(CRAG) of the Scottish Home and Health Departmentare summarised in the Patient care guidelines.

These guidelines should help GPs optimise the risk-bene­fit ratio for prehospital administration of thrombolytics.Ul

However, general aspects of the guidelines are applic­able to the care of patients with suspected acute MIwhether or not the GP has a policy for administering throm­bolytics [e.g. administration of aspirin (acetylsalicylic acid)].

ECG monitoringStrong suspicion of an acute MI is insufficient evi ­

dence to justify the risk of administering thrombolytics. ll]

t In Spain, thrombolytics are available for hospital use only, and arealso carried in emergency ambulances; thus, thrombolytics would notbe administered by GPs. In The Neth erlands, thrombolytics are usuallyadministered in the hospital sett ing, and it is very uncommon for themto be administered by GPs .

// 72-0360/96/00008-00 101$0/ .00 oAdis International Limited. All rights reserved

I Patient with chest pain calls GP..I Call ambu lance if acute myocardial infarct ion is probable

Attend patient at once , taking defibrillator, ECG monitor and thrombo lytic drug...ITake brief history - pat ient conscious with chest pain that is probably ischaemic..

Administer aspir in (acetylsalicylic acid) 300mgGive sublingual nitrog lycerin (glyceryl trinitrate)Insert intravenous cannu la

I If pain is still present administer an intravenous opioid plus an antiemetic 1+

ICons ider other diagnoses IRecord 12· lead ECG

IUnequ ivoca lly abnormal ECGConsider type of abnormality

I

I Normal ECG I

No

ST elevation I Other abnormalities ­Patient severely illand ECG gross ly ischaemicand short time since onset ($2 hours)and long time until hospital review (~ hours)

I

I Do not administer thrombolytics I.n

,. Yes ...

ContraindicationsIndications

Review indications and contrain dicat ions for thrombolytic therapy I

IStrong clinical suspicion of acutemyocard ial infarctionand chest pain for 20 minutesto 12 hours

1

History of cerebrovascular accidentKnown intracrania l pathologyUncontrolled hypertension (>180/11Omm Hg)Bleeding disorder or anticoagulant therapySurgery or majo r trauma within last 10 daysActive gastrointestinal bleedingTraumatic cardiopulmonary resusc itation

Adminis ter thrombolyticsNote: prev ious streptokinase oranistreplase therapy contraindica tesuse of these agents Do not administe r thrombolytics I

~Arrange hospital admissionCheck analgesia , cardiac rate and rhythm . heart failu re, IV cannulaWrite referral note recording details of therapy , especially thrombo lytics if administeredEnsure patient is monitored while being transferred

Guidelines for administration of thrombolytics by general practitioners (GPs![l] © Copyright 1996 Adis International Ltd

ECG is the best and most convenient ancillary diag­nostic aid, although it is not possible to be 100% certainof the diagnosis when the patient is first seen on thebasis of a single ECG recording.Ul Notwithstanding,patients with normal ECGs should not receive thrombo-

lytics, and patients with ST elevation should receivethrombolytics, if no other contraindications apply.

For patients with other ECG abnormalities, consider­ation should be given to additional factors (see Patientcare guidelines), remembering that the risk-benefit profile

1172-0360/96I00008-00 1l1$01.00 '"Adis International limited. All rights reserved VoL 7, No.8; April 29, 1996

-

Features Alteplase (rt -PA) An istreplase St reptokinase Urokinase

Ant igen icity : requ ires history of prev ious x .18 .Ia x

administration , and should not be reused if>5 days has elapsed since first administration

Duration of IV administration (minutes) bolus then 60 4-5 60 Bolus

Requires concomitant heparin administration .I x x x

Needs to be kept refrigerated at all times x .I x x

Acqu isi tion costs for usual dosages

In the UK (£) 750 495 80-85 460

a Cross antigenicity is seen with anistreplase and streptokinase.Abbreviations and symbols : IV =intravenous; rt-PA =recombinant tissue-type plasminogen activator; x =no; ./ =yes.

is likely to be more favourable for early therapycompared with late therapy (~12 hours post-Mlj.Ul

Requirement for a defibrillator

It has been recommended that a defibrillator be avail­able when thrombolytics are administered.I-l becauseadministration of thrombolytics slightly increases therisk of ventricular fibrillation and cardiac arrest.Ul Thishas been given as a reason for the reluctance of GPs toadminister thrombolytics, as defibrillators are expensiveand can be cumbersome to transport.

However, acute MI has a 28-day mortality rate of 50%and over half of the deaths occur in the first 2 hours afterthe onset of symptoms. Thus, if a rapid response is madeto patients with suspected acute MI, cardiac arrest willoften be encountered, and use of a defibrillator improvesthe survival rate in these patients) I] Therefore, it could beargued that a defibrillator should be available whether ornot the GP has a policy on administering thrombolytics.

In addition, it will not be necessary for the GP to owna defibrillator if the policy is for a combined responsefrom both an emergency ambulance (which carries adefibrillator) and the GP attending the patient.l-l

Which thrombolytic?Convenience and cost are the main considerations in

selecting a thrombolytic agent for use in general practice(see Differential features table) .

The differences in efficacs] and safety betuieen

tile agents are minor compared uiitlt tileincreased benefits ofgiving /lilY agent tuitltin

the recommended time limit. I I)

Vol. 7, No.8; April 29, 1996

At present, alteplase appears the least likely to be pre­ferred because of its high cost and complicated infusionregimen.IU

Anistreplase has been used in clinical trials of GPthrombolytic administration, and has been shown to besafe and effective)4,5] However, its requirement forconstant refrigeration limits its convenience.Ul

Streptokinase is the least expensive agent , but it requiresadministration by intravenous infusion over 1 hour.U]

Urokinase has a number of ideal features in that it isnon-antigenic, may be administered by bolus injectionand does not have to be refrigerated. However, comparedwith the other agents, urokinase has been much less ex­tensively used and evaluated in patients with acute MUI]

Risks of thrombolyticsThrombolytic therapy is associated with an excess risk

of stroke of approximately 0.3 to 0.7%.[1]This risk is the major consideration in the risk-benefit

evaluation of thrombolytic therapy. For example, anumber of risk factors for cerebral haemorrhage, such asa history of cerebral vascular haemorrhage and uncon­trolled hypertension, are contraindications to thrombo­lytic therapy.

However, the risk of cerebral haemorrhage with throm­bolytics is not related to the time of administration afteronset of symptoms of acute MI. In addition, the benefits ofthrombolytics are greater the sooner they are administered.Thus, for those patients with no absolute contraindicationsto thrombolytic therapy, earlier administration of thrombo­lytics will actually improve the risk-benefit ratio.Ul

It has been estimated that prehospital administrationof thrombolytic therapy at the first opportunity has abetter than 1 in 10 chance of saving a life with an excessrisk of disabling stroke of 1 in 1000.[1]

OO8·0012/$01.00סס/0360196·1/72 ©Adis 1nternational limited. All rights reserved

Do not forget aspirinEven if GPs have a policy of not administering throm­

bolytics, they must be able to provide aspirin, nitratesand adequate analgesia, preferably with an intravenousopioid.l-l

Administration of aspirin reduces the risk of thepatient dying, although why this is so is unclear.f2l Thus,patients who have not taken any aspirin in the previous24 hours should chew a 300mg tablet, unless there is aclear contraindication.f2J

In addition, patients with chest pain suggestive ofmyocardial ischaemia should be administered sublingualnitrates unless they have already self-administered largedoses or they have hypotension (systolic blood pressure<90mm Hg»)2)

Relief of pain with intravenous opioids may alsoameliorate cardiogenic shock, as well as improvingpatient comfort and reducing anxiety.Ul

ReferencesI. Rawles J. Guidelines for general practitioners administering

thrombolytics. Drugs 1995 Oct; 50(4): 615-252. Weston CFM, Penny WJ, Julian DG, on behalf of the British Heart

Foundation working group . Guidelines for the early managementof patients with myocardial infarction . Br Med J 1994 Mar 19;308: 767-71

3. British National Formulary No. 30. London : The PharmaceuticalPress, 1995 Sep; 108-9

4. Hannaford P, Vincent R, Ferry S, et al. Assessment of the practicalityand safety of thrombolysis with anistreplase given by generalpractitioners. Br J Gen Pract 1995 Apr; 45: 175-9

5. GREAT Group . Feasibility, safety, and efficacy of domiciliarythrombolysis by general practitioners: Grampian region earlyanistreplase trial. Br Med J 1992; 305: 548-53

Aims and scope of Drugs & TherapyPerspectives:• To provide timely overviews of new drugs ,

incorporating comparative data with establishedagents

• To report on new developments and internationalconsensus on drug use in disease management

• To advise on the avoidance and management ofadverse drug reactions and interactions

• To inform readers of developments inpharmacoeconomics and outcomes research thathave a bearing on clinical practice

Key features of the publication include:

• Differential Features tables - to provide a basisfor formulary comparisons of products

• Patient Care Guidelines - for use in diseasemanagement and drug usage evaluation

• Adis evaluation tables - for a rapid appraisal ofthe benefits and limitations of drugs and drugclasses

OO8-00131$01.00סס/1172-0360/96 cAdis International Limited. All rights reserved

DrugsTIItllIf'II H'r5prt t,,~~ /3-Home IV anti-infective therapy an

attractive alternative to inpatientmanagement

With the increasing emphasis on the economic aspectsof healthcare provision, there has been growing interestin the administration of antimicrobials via home intrave­nous anti-infective therapy (HIVAT),l! I and it is rapidlybecoming an accepted mode of treatment worldwide.f2J

In the US, HIVAT therapy currently costs around$US2.5 billion annually.Pl An estimated 250 000 Ameri­cans receive HIVAT each year, and the market is growingat 10% annually.l-l

To be successful, HIVAT requires an integrated teamapproach among patients, pharmacists, physicians andnurses, combined with careful patient selection, a struc­tured follow-up process and patient education) 1,2]

In the US, the emphasis is on patient self-administra­tion of anti-infectives at home, whereas in Europe it ismore common for physicians or nurses to administer anti­infectives in a hospital outpatient setting.

However, certain questions arise regarding the cost, qual­ity of care, method of standardisation and monitoring, andthe cultural acceptance of home-based therapy.Hl

Thus, it is important to weigh up the potential benefitsand risks to the individual patient before undertakingHIVAT (see table 1).

Key elements for HIVATThe key elements for a successful HIVAT programme

comprise:[2]

• knowledgeable primary care physicians• infectious disease specialists with a particular interest

in home IV anti-infective therapy

• pharmacists familiar with drug stability, drug interac-tions and storage issues

• an IV nurse team (for IV cannula and ongoing care)• a willing and compliant patient

• a clear communication system to relay informationand concerns.

Selecting the right patientsPatient selection for HIVAT is a vital step. Patients

should become eligible for HIVAT only after they haveundergone all appropriate medical and surgical proce­dures, and are clinically stable)I,5]

In addition, patients should have a clear need for anIV anti-infective (e.g . no suitable oral alternative, oraltherapy not appropriate), a clearly defined illness thatcan be managed at home, an underlying disease that is

Vol. 7, No.8; April 29, 1996