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Management

Pre-hospital Care

Most deaths associated with AMI occur within first hour of its onset and are usually due to ventricular fibrillation. Hence the importance of immediate implementation of definitive resuscitative efforts and rapid transport of the patient to a hospital cannot be over emphasized.

Establishment of a pre hospital fibrinolysis protocol is reasonable in:

1) Settings in which physicians are present in the ambulance or

2) In well organized Emergency Medical Services (EMS) systems with full time paramedics who have 12-lead ECG on line.

Randomized controlled trials of fibrinolytic therapy have demonstrated the benefit of initiating fibrinolytic therapy as early as possible after diagnosis of STEMI. Transport time to the hospital is variable from case to case, but the goal is to keep total ischaemic time within 120 minutes.Patients with STEMI who have cardiogenic shock and are < 75 yrs of age and patients who have
contra indication (CI) for thrombolysis should be brought immediately or secondarily transferred to facilities capable of cardiac catheterisation and rapid revascularisation or CABG if it can be performed within 18 hrs of onset of shock.

Management in the Emergency Department

Hospitals should establish multidisciplinary teams (including primary health care physicians,emergency medicine physicians, cardiologist nurses and laboratorians) to develop a guideline based, institution specific written protocol for triaging and managing these patients.The goal for patients with STEMI should be to achieve a door to needle time (for thrombolysis) within 30 mts and a door to balloon time (for primary PCI) within 90 mts.Routine Measures

a)Oxygen

Supplemental oxygen should be administered to patients with arterial oxygen desaturation (Sa O2 <90 per cent) (ClassI). It is reasonable to administer supplemental O2 to all patients with uncomplicated STEMI during the first 6 hrs. (Class II a).
 
Dose: 2-4 l/mt of 100 per cent O2 by mask or nasal prongs for 6-12 hrs.

b)Nitroglycerine

NTG is indicated for ongoing chest discomfort, control of hypertension and management of pulmonary congestion.

Dose: S/L NTG - 0.4 mg every 5 mts for a total 3 doses or IV NTG 5ug/mt infusion

Contraindications

BP < 90 mm of Hg

> 30 mm of Hg below baseline BP

Bradycardia < 50 bpm

Tachycardia > 100 bpm

Suspected RV infarction.

c)Analgesia

Most important initial objective is relief of pain. Morphine is an extremely effective analgesic. It also reduces sympathetically mediated arteriolar and venous contriction.Hypotension associated with venous pooling usually responds to elevation of legs.Morphine also has vagotonic effect and may cause bradycardia. This responds usually to IV atropine.

Dose: Morphine sulphate 2-4 mg with increments of 2-8 mg IV repeated at 5-15 mts intervals.

d)Aspirin

Aspirin produces a rapid clinical antithrombotic effect caused by immediate and near total inhibition of thromboxane A2 production. It has become an integral part in the treatment of AMI. A 23 per cent reduction in mortality at 35 days in patients treated with aspirin during early stages of AMI was observed in ISIS-2 trial.Aspirin should be avoided in cases of true hypersensitivity. In the case of bleeding from peptic disease, rectal suppositories can be used. Ticlopidine can be used in cases were aspirin in contraindicated.

Dose: 162-325 mg plain aspirin chewed preferably and not swallowed.

e)Beta Blockers (BB)
Analysis of pooled data from 28 trials revealed an average reduction of mortality of 28 per cent at 1st week and majority of the benefit was seen in the first 48 hrs. Immediate BB therapy appears to reduce the magnitude of infarction and limits infarct size. Othercommendable actions are it reduces ventricular ectopy, atrial fibrillation and non-fatal cardiac arrest. It reduces recurrent ischaemia and infarction during first 6 weeks after initial event.

Oral beta blockers therapy should be administered promptly to all patients without a contrainidication. Other indications are the presence of tachyarrhythmia or hypertension.

Dose: Betablocker of choice is Metoprolol. Beta blockers most often used are Atenolol and Metoprolol. These can be administered intravenously (Atenolol 5-10 mg IV bolus × 2/Metaprolol 5 mg bolus × 3 at 5 mts apart) followed by oral administration (Atenolol upto 100 mg daily/metoprolol 50 mg twice daily).

Relative contraindications for the use of BB are:

1) Patients with heart failure (rales > 10 cm up from diaphragm)

2) Hypotension (SBP < 90 mm of Hg),

3) Bradycardia (HR< 60 bpm), or

4) Heart block (PR > 240 ms, 2nd and 3rd degree HB)

f)Angiotension Converting Enzyme Inhibitors/Angiotension Receptor Blockers (ACEI/ARB) A large number of randomized clinical trials have assessed the role of ACEI early in the course of acute MI. All trials with oral ACE inhibitors have shown benefit from their early use. ACEI should be started within first 24 hrs. It should not be used if SBP is less than 100mmHg or less than 30mmHg below baseline or if there are other contraindication to ACEI. Some of the drugs dosages are as follows:

Starting dose   Recommended Max      Dose

Captopril 6.25 mg tds 50 mg tds

Enalapril 2.5 mg bd 10 mg bd

Ramipril 2.5 mg bd 10 mg bd

Indications
1) All patients with anterior wall MI.

2) Pulmonary Congestion.

3) LVEF < 40 per cent.

ARB should be administered for those intolerant to ACEI. Valsartan and Candesartan have also established efficacy.

g)Ca Channel Blockers
Generally not used in the setting of acute MI. Only indication is in patients in whom beta- blockers are ineffective or contraindicated for relief of ongoing ischaemia or control of a rapid ventricular response with atrial fibrillation or flutter in the absence of CHF, LV dysfunction or atrioventricular block. Calcium channel blocker of choice is Verapamil or Diltiazem. Nifedipine (immediate release form) is contraindicated in STEMI.h)

Thrombolytic Therapy

Thrombolytic agents have been shown to limit infarct size, preserve ventricular function and improve infarct size. The impact of early treatment was first clearly shown in the initial GISSI trial and confirmed in ISIS-2. Trials have shown that benefits of thrombolytic therapy are directly related to achievement of early reperfusion.

i)Mechanism of Action

All of the so called thrombolytic agents are either direct or indirect activators of plasminogen, a circulating proenzyme. Plasminogen is converted by plasminogen activators or activator complexes to plasmin, the active fibrinolytic enzyme. Plasmin has relatively broad proteolytic properties, degrading fibrin, fibrinogen, prothrombin and factors V and V11. Plaminogen activators induced fibrinolysis may then act to disrupt thrombus.

ii) Indications
1) To all STEMI patients with symptom onset within the prior 12 hrs and ST elevation greater than 1mm in at least 2 contiguous precordial leads or at least 2 adjacent limb leads, or new onset LBBB in the absence of contraindiations.

2) To all STEMI patients with symptom onset within prior 12 hrs and new or presumably new LBBB, in the absence of contraindications.

3) To STEMI patients with symptom onset within the prior 12 hrs and 12 lead ECG findings consistent with true and posterior MI, in the absence of contraindication.

In the absence of contraindication, it is reasonable to administer fibrinolytic therapy to patients with symptoms of STEMI beginning within the prior 12-24 hrs who have continuing ischaemic symptoms and ST elevation.

iii) Contraindications (CI)

Absolute Contraindications

1) Any prior intra cranial hemorrhage.

2) Known structural cerebral vascular lesions (AVM).

3) Known malignant intracranial neoplasm.

4) Ischaemic stroke within 3 months.

5) Suspected aortic dissection.

6) Active bleeding diathesis (excluding menstruation which is not a contraindication).

7) Significant closed head or facial trauma within 3 months.

Relative Contraindications

1) History of c/c severe, poorly controlled hypertension.

2) Severe uncontrolled hypertension on presentation (SBP >180 mm of Hg or DBP > 110 mm of Hg).3) H/o prior ischaemic stroke > 3 months, dementia or known intracranial pathology not covered in contraindication.

4) Traumatic or prolonged (>10 mts) CPR or major surgery (less than 3 weeks).

5) Recent internal bleeding (2-4 wks).

6) Non compressible vascular punctures.

7) For streptokinase: prior exposure (more than 5 days ago) or prior allergic reactions to the agent.

8) Pregnancy.

9) Active peptic ulcer.

10) Current use of anticoagulants. The higher the INR, the higher the risk of bleeding.

iv) Choice of Thrombolytic Agent

Four thrombolytic agents have been approved for routine use.

1) Streptokinase (SK)

2) rt- PA

3) APSAC

4) r-PA (reteplase)

1) Streptokinase: This is a non-enzyme protein of mw (47,000-50,000) produced by several strains of hemolytic streptococci. Streptokinase activates plasminogen to plasmin indirectly. It is antigenic and has little fibrin specificity.A few days after administration of SK, antistreptokinase titer rises rapidly to 50-100 times and remains high for 4-6 months during which period renewed treatment with SK is impracticable.

Dose: 1.5million units IV over 30-60 mts.

2)t-PA: Native tissue-type plaminogen activator (t-PA) is a serine proteinase with a molecular weight of about 70,000. t-PA for clinical use is presently produced by recombinant DNA technology. The high affinity of t-PA for plasminogen in the presence of fibrin allows efficient activation on the fibrin clot, while no efficient plasminogen activation by t-PA occurs in plasma. Its half-life is about 5 mts.

Dose: Initial bolus of 15 mg followed by an infusion of 50 mg or 0.75 mg/kg body weight over the next 30 mts and an infusion of 35 mg or 0.5 mg/kg body weight over the subsequent 60 mts, for a total of up to 100 mg over 90 mts.

3)APSAC: (Anisolylated plasminogen–SK complex) Although APSAC is identical to SK as a thrombolytic agent, it can be given as a rapid infusion. Its therapeutic half-life is similar to that of SK, which is about 90 mts.

Dose: 30 mg over 5-10 mts.

4)Reteplase (r-PA): This is a single chain non glycosylated deletion variant of r-PA consisting only of the kringle 2 and protenase domain of human t-PA. Both t-PA and r-PA have almost similar efficacy and safety. Retelplase has a longer half-life.Dose: 2 doses of 10 units each 30 minutes apart to be given over 2 minutes.

5) Other Agents

Urokinase: It has similar efficiency and safety to Streptokinase and is more approved for routine use, it was widely used as an intracoronary and intravenous agent.

Prourokinase (saruplase): It is a naturally occurring glycoprotein that is rapidly converted into urokinase by plasmin. But not approved for routine use.TNK- t-PA: It has increased fibrin specificity and resistance to plasminogen
activator inhibitor-1.

Lanoteplase (n-PA): The half-life of n-PA is 23 mts. This is administered as a bolus.

Staphylokinase: It has marked fibrin specificity and is administered in a dose of 20-30 mg in 30 mts. Repeat administration is not advisable due to immunogenecity.

Chimeric Plasminogen Activators

K1 K2 P4: This agent consists of bits of t-PA and SCU-PA to form a single compound with the help of recombinant technology. This results in marked enhancement of thrombolytic acitivity.

FK 2 tu-PA and K 2 tu-PA are other chimeric agents.

v) Selection of Reperfusion Strategy

Several issues should be considered in selecting the type of Reperfusion therapy.

Step I: Assess Time and Risk

• Time since onset of symptoms.

• Risk of STEMI.

• Risk of fibrinolysis.

• Time required for transportation to a sterilized cardiac catheterisation lab.

Step II

Determine whether fibrinolysis or invasive strategy is preferred. If presentation is < 3 hrs and there is the delay to an invasive strategy, there is no preference for either strategy.

Fibrinolysis is generally preferred.

• Early presentation (3 hrs or less from symptom onset and delay to invasive strategy).

• Invasive strategy is not an OPTION

— Catheterisation laboratory occupied or not available.

— Vascular access difficulties.

— Lack of access to a skilled PCI lab.•

Delay to invasive strategy.

—Prolonged transport.

(Door-to-Balloon)-(Door-to-Needle) time is greater than 1 hr.

—Medical contact-to-balloon or door-to-balloon time is greater than 90 minutes

An invasive strategy is generally preferred if:

•Skilled PCI laboratory available with surgical backup.

•Medical contact-to-balloon or door-to-balloon time less than 90 minutes.

High risk from STEMI.

— Cardiogenic shock

— Killip class greater than or equal to 3.

• Contraindications to fibrinolysis, including increased risk of bleeding and ICH.

• Late presentation.
—Symptom onset was more than 3 hrs ago.

• Diagnosis of STEMI is in doubt.

With delayed PCI, the mortality benefit decreases, compared with a fibrin-

specific lytic agent. A PCI strategy may not reduce mortality when a delay greater than 60 mts is anticipated versus immediate administration of lytic agent.

vi) Indications of Successful Reperfusion

1) Relief of symptoms.

2) Maintainence of haemodynamic and or electrical stability.

3) A reduction of at least 50 per cent of the initial ST-Segment elevation at 60-90mts.

Rescue PCI

Rescue PCI refers to PCI within 12 hrs after failed fibrinolysis for patients with continuing or recurrent myocardial ischaemia.
Indications for Rescue PCI

1) In patients less than 75 yrs old who develop shock within 36 hrs of MI and are suitable for revascularisation that can be performed within 18 hrs of shock.

2) In patients with severe CHF or pulmonary oedema (Killip class 111) and onset of symptoms within 12 hrs.Facilitated PCIFacilitated PCI refers to a strategy of planned immediate PCI after an initial pharmacological regimen such as full-dose fibrinolysis, half-dose fibrinolysis, a GP IIb/IIIa inhibitor or a combination of reduced-dose fibrinolytic therapy and a GP I1b/IIIa inhibitor. A strategy of facilitated PCI holds promise in higher-risk patients when PCI is not immediately available.

Potential complications are:

1) Increased bleeding complications.

2) Added cost.

Indication for Emergency or Urgent Coronary Artery Bypass Grafting (CABG) in AMI

1) Failed PCI with on going ischaemia or haemodynamic instability.

2) In patients who are not candidates for fibrinolytic therapy or PCI and who have persistent ischaemia refractory to medical therapy, with a significant area of myocardium at risk.

3) At the time of surgical repair of post infarction VSD or mitral valve insufficiency.

Indication for Unfractionated Heparin (UFH) in AMI
1) In all patients undergoing PCI or surgical revascularisation.

2) In patients undergoing reperfusion therapy using fibrin selective agents.

3) In patients treated with non-selective fibrinolytic agents, UFH is indicated if they are at high risk for systemic embolisation (large anterior MI, atrial fibrillation, previous embolism,known LV thrombus).

Dose: 60u/kg (4000 u maximum) followed by initial infusion of 12u/kg/hr (max 1000u/hr) Maintain APTT at 1.5-2 times control.

Indications of Low Molecular Weight Heparin (LMWH) in AMI It may be considered as an acceptable alternative to UFH. It is not recommended in patients over 75 yrs who are receiving fibrinolytic therapy or in presence of renal dysfunction.

Indications for Invasive Cardiac Monitoring in AMI

1) Indications for Pulmonary artery (PA) catheter.

2) Progressive hypotension, when unresponsive to fluid administration or when fluid administration may be contraindicated.

3) Suspected mechanical complications of STEMI.

4) Indications for intra-arterial pressure measurement

a)Patients with severe hypotension (SBP < 80 mmHg).

b) Patients receiving vasopressor/inotropic agents.

c)Cardiogenic shock.
A preshock state of hypoperfusion with normal blood pressure may develop before circulatory collapse. This is manifested by cold extremities, cyanosis, oliguria or decreased mentation.Hospital mortality is high; so these patients should be aggressively diagnosed and treated as though they are in cardiogenic shock.

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