Dott. Maurizio M. Ciammaichella

Dirigente Medico
Responsabile UAS “Trombosi Venosa Profonda ed Embolia Polmonare”
Responsabile CDF BLSD IRC “Emersan Lateranum”
U.O.C. Medicina Interna I° per l'Urgenza

(Direttore: Dott. G. Cerqua)
A.C.O. S. Giovanni - Addolorata - Roma

CARDIOGENIC SHOCK

KEY-WORDS: Cardiogenic shock

INTRODUCTION
CLINICAL
WORKUP
TREATMENT
MEDICATION
FOLLOW-UP
MISCELLANEOUS
BIBLIOGRAPHY

INTRODUCTION

Background: Cardiogenic shock is characterized by a decreased pumping ability of the heart causing a shock-like state with inadequate perfusion to the tissues. It occurs most commonly in association with, and as a direct result of, acute ischemic damage to the myocardium.

Although shock is considered to be a clinical diagnosis, useful physiologic parameters include a systolic blood pressure less than 80 mm Hg, cardiac index less than 1.8 L/min/m2 and a pulmonary capillary wedge pressure greater than 18 mm Hg.

Pathophysiology: The most common initiating event in cardiogenic shock is acute myocardial infarction (AMI). A dead myocardium simply does not contract, and once more than 40% of the myocardium has become involved, cardiogenic shock may result.

On a mechanical level, a marked decrease in contractility results in a reduction in ejection fraction and cardiac output. This leads to the development of increased ventricular filling pressures, cardiac chamber dilation and ultimately uni- or biventricular failure resulting in systemic hypotension and/or pulmonary edema.

Cardiogenic shock occurs via a cascade of events and positive feedback loops. Hypoperfusion results in the release of a variety of endogenous substances including: myocardial depressant factor (MDF), histamine, bradykinin, thromboxane, cytokines, leukotrienes, platelet activating factor and lactic acids. These factors further inhibit cardiac function, thereby, increasing myocardial depression and worsening the shock state thereby increasing their own release.

There is an extensive body of literature supporting the existence of endogenously produced myocardial depressant factor (MDF). MDF is a low molecular weight protein believed to be released from pancreatic lysosomes during shock-like states. MDF causes direct myocardial depression by an as yet to be identified mechanism.

Similar events occur on a more macro level as well. Myocardial ischemia causes a decrease in the contractile function, which leads to LV dysfunction and decreased arterial pressure, which in turn exacerbates the myocardial ischemia and so on. The end result for these pathways is a viscious cycle leading to severe cardiovascular decompensation.

Frequency:

In the U.S.: Cardiogenic shock occurs in approximately 5-10% of patients with acute myocardial infarction.

.Mortality/Morbidity:

Mortality rates for medically treated AMI patients with cardiogenic shock exceed 70%.

Outcomes are improved significantly only when rapid revascularization can be achieved.
Individual rates vary depending on the procedure (e.g., PTCA, stent placement, and thrombolytics), but have been reported to be as low as 30-50%.

CLINICALPATHOPHYSIOLOGY

History:

Most patients presenting with cardiogenic shock do so in conjunction with an AMI and, therefore, present with the constellation of symptoms of acute cardiac ischemia (e.g., chest pain, shortness of breath, diaphoresis, nausea and vomiting).
Patients experiencing cardiogenic shock may also present with pulmonary edema and presyncopal or syncopal symptoms.

Physical:

Physical examination will often reveal a patient in the throes of an AMI.

Patients appear in frank extremis, profoundly diaphoretic and complaining of severe shortness of breath and chest pain.

Clinical assessment begins with attention to the ABCs and vital signs.

Although the patient may eventually require endotracheal intubation, the airway is usually patent, at least initially.

Breathing may be labored and there may be audible coarse crackles or wheezing.

As in any shock-like state, circulation is markedly impaired.

Patients present with marked tachycardia, cool and clammy extremities, poor peripheral pulses and varying degrees of end-organ dysfunction (e.g., decreased mental function and urinary output).

Initial vital signs should include blood pressures in both arms to evaluate for the possibility of thoracic aortic aneurysm or dissection and should be regularly updated via continuous noninvasive physiologic monitoring.

Neck examination may reveal jugular venous distention as evidence of right ventricular failure and may be prominent.

With increasing degrees of ventricular dysfunction, florid pulmonary edema and severe hypotension may develop.

Auscultation of the chest may reveal varying degrees of congestive heart failure (CHF).

Careful attention should be directed toward the cardiac examination, as there are mechanical causes of cardiogenic shock which are readily amenable to surgical intervention, and without which the mortality is dismal.

These include papillary rupture, valvular dysfunction, myocardial wall or septal rupture, cardiac tamponade and aortic aneurysm.

Loud murmurs may indicate a valvular dysfunction while muffled heart tones with JVD and pulsus paradoxus may suggest tamponade.

Causes:

The vast majority of cases of cardiogenic shock are directly due to acute myocardial ischemia.

Other related causes include:

Toxic (drugs such as, Adriamycin)

Infectious/inflammatory (acute myocarditis)

Pharmacologic (e.g., beta blockers, calcium channel blockers)

Mechanical (e.g., valvular dysfunction, tamponade, and cardiomyopathy)

Risk factors for the development of cardiogenic shock include pre-existing myocardial damage or disease (e.g., diabetes, advanced age, previous MI) - Q-wave, larger sized, or anterior wall MIs - and dysrhythmia.

WORKUP

Lab Studies:

There is no one test completely sensitive or specific for cardiogenic shock. Laboratory studies are directed at the potential underlying cause.

In most cases the usual work up will include all of those tests usually used in cases of suspected cardiac ischemia.

These include cardiac enzymes (creatine phosphokinase [CPK], troponin and/or myoglobin), complete blood count (CBC), electrolytes and a coagulation profile (e.g., PT, APTT).

An arterial blood gas (ABG) may be useful to evaluate acid-base balance as acidosis can have a particularly deleterious effect on myocardial function.

.Imaging Studies:

A portable chest x-ray (CXR) is helpful for a number of reasons.

It gives an overall impression of the cardiac size, pulmonary vascularity, and coexistent pulmonary pathology.

It gives a rough estimate of the mediastinal and aortic sizes in the event that an aortic etiology is being considered.

Other Tests:

An electrocardiogram (ECG) is very helpful if it reveals an acute injury pattern consistent with an AMI. A normal ECG, however, does not rule out the possibility. ECGs are often most helpful when they can be compared to previous tracings.

An echocardiogram obtained in the ED can be extremely useful.

It may be diagnostic and reveal akinetic or dyskinetic areas of ventricular wall motion.

It may reveal surgically correctable causes, such as valvular dysfunction and tamponade.

.Procedures:

Placement of a central line may be advisable to facilitate volume resuscitation, provide vascular access for multiple infusions and allow for invasive pressure monitoring of CVP and PCWP. Although not necessary for the diagnosis of cardiogenic shock, invasive monitoring with a pulmonary artery catheter may be helpful in guiding fluid resuscitation in difficult situations in which it is difficult to determine LV preload.

TREATMENT

Prehospital Care:

Prehospital care is aimed at minimizing any further ischemia and shock.

All patients require IV access, high flow oxygen by mask, and a cardiac monitor.

Care is then supportive and similar to that outlined below, depending on the level of provider and ability to perform certain maneuvers.

Emergency Department Care:

ED care is aimed at making the diagnosis, preventing further ischemia and treating the underlying cause. As always, treatment begins with assessment of the airway, breathing and circulation.

Once these have been managed, and while supportive measures are underway, an early focus should be on reversing the underlying cause. In most cases that means attention to revascularization. The method by which it is achieved will vary according to locale and institution. If there is a cath laboratory readily available, better outcomes have been achieved with revascularization via PTCA with or without stent placement. If there is no cath laboratory available, the next best option is for thrombolytic therapy, given that there are no contraindications to its use.

The common theme of preventing further ischemia and supportive care has a variety of implications in these patients. They require oxygen, IV fluids, close cardiac and hemodynamic monitoring. Providing high flow oxygen, decreasing myocardial oxygen consumption and increasing perfusion to the ischemic myocardium may reduce ischemia. Extremes of heart rate should be avoided as they may increase myocardial oxygen consumption, increase infarct size, and further worsen the pumping ability of the heart.

There are a variety of pharmacologic interventions, which may be advisable depending on the individual circumstance.

Nitrates and/or morphine are advisable for management of pain; however, they must be used with caution as these patients are by definition in shock, and too much of either of these agents can produce profound hypotension.

Vasopressor support may be provided using dopamine. At higher doses, it has the disadvantage of increasing heart rate and myocardial oxygen consumption.

Dobutamine, amrinone or milrinone may provide inotropic support. In addition to their positive inotropic effects, amrinone and milrinone have the additional beneficial effect as a vasodilator, reducing preload and afterload.

Beta-blockers have been shown to be cardioprotective and should be used unless contraindicated (e.g., heart rate less than 50 or systolic BP less than 90).

Counterpulsation intraaortic balloon pump (IABP) has been used for a number of years for severe, refractory cardiogenic shock not amenable to other maneuvers. Although initially held to be life-saving, recent evidence has failed to demonstrate any clear improvement in long-term outcomes.

.Consultations:

A cardiology consultation should be obtained at the earliest possible opportunity. While providing echocardiographic support and facilitating transfer to definitive care (cath lab, ICU, OR), their insight and expertise can be invaluable.

MEDICATION

To improve cardiac contractility, dopamine and dobutamine are the drugs of choice. To improve cardiac output for refractory hypotension and shock, milrinone and amrinone may be used.

Drug Category: Vasopressor - These drugs augment both coronary and cerebral blood flow present during the low flow state associated with shock. Sympathomimetic amines with both alpha- and beta-adrenergic effects are indicated.

Drug Name	Dopamine - It stimulates both adrenergic and dopaminergic receptors. It's hemodynamic effect dependent on the dose. Lower doses stimulate mainly Dopaminergic receptors that produce renal and mesenteric vasodilation are stimulated by lower doses of dopamine. Cardiac stimulation and renal vasodilation is produced by higher doses. After initiating therapy, may increase the dose by 1-4 mcg/kg/min every 10-30 min until the optimal response is obtained. More than 50% of patients are satisfactorily maintained on doses less than 20 mcg/kg/min.
Adult Dose	Administer a continuous 5.0-20 mcg/kg/min IV infusion
Pediatric Dose	Administer a continuous 5.0-20 mcg/kg/min IV infusion
Contraindications	Avoid use in patients with documented hypersensitivity to sulfites or related products and those diagnosed with pheochromocytoma or ventricular fibrillation.
Interactions	Phenytoin, alpha- and beta-adrenergic blockers, general anesthesia, and MAO inhibitors increase and prolong the effects of this medication.
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Tachycardia resulting from this treatment may cause untoward increase in myocardial oxygen consumption. Ventricular dysrhythmias also occur. Monitor closely the urine flow, cardiac output, pulmonary wedge pressure, and blood pressure during the infusion. Prior to infusion, correct hypovolemia with either whole blood or plasma, as indicated. Monitoring of central venous pressure or left ventricular filling pressure may be helpful in detecting and treating hypovolemia.

Drug Name	Dobutamine - It is a sympathomimetic amine with stronger beta than alpha effects. Produces vasodilation and increases the inotropic state. At higher dosages may cause an increased heart rate, thus exacerbating myocardial ischemia.
Adult Dose	Administer a continuous 5.0-20 mcg/kg/min IV infusion
Pediatric Dose	Administer a continuous 5.0-20 mcg/kg/min IV infusion
Contraindications	Avoid using in patients with documented hypersensitivity to sulfites or related products and those diagnosed with idiopathic hypertrophic subaortic stenosis and atrial fibrillation or flutter.
Interactions	I Beta-adrenergic blockers antagonize the effects of nitroprusside. Conversely, general anesthetics may increase its toxicity.
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Following a myocardial infarction use dobutamine with extreme caution. A hypovolemic state should be corrected before using this drug.

Drug Category: Phosphodiesterase enzyme inhibitors - Bipyridine, with phosphodiesterase inhibitors, can have positive inotropic activity and little chronotropic activity.

Drug Name	Milrinone (Primacor) - It is a bipyridine, positive inotrope and vasodilator, with little chronotropic activity. It is different in mode of action from either the digitalis glycosides or catecholamines.
Adult Dose	50 mcg/kg IV loading dose over 10 min followed by continuous infusion at 0.375-0.75 mcg/kg/min
Pediatric Dose	Use the same regimen as in adults. However, although it is used as the drug of choice in many pediatric intensive care units, safety and efficacy have not been well established.
Contraindications	Avoid use in patients with documented hypersensitivity to this medication or related products.
Interactions	It precipitates in the presence of furosemide.
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Monitor fluid, electrolyte changes and renal function during therapy. Excessive diuresis may cause an increase in potassium loss and predispose digitalized patients to arrhythmias. It is important to correct hypokalemia by potassium supplementation prior to treatment. Patients showing excessive decreases in blood pressure should have their infusion rate slowed or stopped. If a vigorous diuretic therapy has caused significant decreases in cardiac filling pressure, in the past, cautiously administer milrinone, and monitor blood pressure, heart rate and clinical symptomatology.

Drug Name	Amrinone (Inocor) - It is a phosphodiesterase inhibitor with positive inotropic and vasodilator activity. It produces vasodilation and increases the inotropic state. It is more likely to cause tachycardia than dobutamine. This may exacerbate myocardial ischemia.
Adult Dose	Administer a 0.75 mg/kg IV bolus slowly over 2-3 min. The maintenance infusion is 5.0-10 mcg/kg/min. Do not exceed 10 mg/kg The dose should be adjusted according to patient response.
Pediatric Dose	Administer the same regimen as in adults. However, safety and efficacy have not been established.
Contraindications	Avoid use in patients with documented hypersensitivity to amrinone, lactate, sulfites, or related products.
Interactions	Diuretics may cause significant hypovolemia and a decrease in filling pressure. Amrinone also has additive effects when used concurrently with cardiac glycosides.
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Causes thrombocytopenia in 2-3% of patients. Hypotension may occur following the loading dose and thus it requires adequate preload. Ventricular dysrhythmias may occur, however, it may be related to the underlying condition. It should not be used in patients with cardiac outlet obstruction (e.g., aortic stenosis, pulmonic stenosis, and idiopathic hypertrophic subaortic stenosis/hypertrophic cardiomyopathy). Discontinue therapy if clinical symptoms of liver toxicity occur. Correct hypokalemic states before using amrinone.

Drug Category: Vasodilators - These agents are smooth muscle relaxers and vasodilators that can reduce SVR, allowing more forward flow, improving cardiac output.

Drug Name	Nitroglycerin - It causes relaxation of the vascular smooth muscle via stimulation of intracellular cyclic guanosine monophosphate production.
Adult Dose	Administer a continuous 10-20 mcg/min IV infusion
Pediatric Dose	Administer a continuous 0.1-1.0 mcg/kg/min IV infusion
Contraindications	Avoid use in patients with documented hypersensitivity to this medication or related products and those diagnosed with severe anemia, closed angle glaucoma, postural hypotension, head trauma or cerebral hemorrhage.
Interactions	Aspirin may increase nitrate serum concentrations and actions may occur. Marked symptomatic orthostatic hypotension may occur when administered concurrently with calcium channel blockers and an adjustment in the dose of either agent may be necessary.
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Exercise caution in patients with coronary artery disease, and low systolic blood pressure.

Drug Category: Analgesics - Pain control is essential to quality patient care. It ensures patient comfort, and promotes pulmonary toilet. Most analgesics have sedating properties, which are beneficial for patients who have sustained painful skin lesions.

Drug Name	Morphine Sulfate - It is the DOC for narcotic analgesia due to its reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Morphine sulfate administered iv may be dosed in a number of ways and is commonly titrated until the desired effect is obtained.
Adult Dose	Starting dose: 0.1 mg/kg IV, IM, sc Maintenance dose: 5-20 mg/70 kg q4h IV, IM, sc Relatively hypovolemic patients: Start with 2 mg IV, IM, sc, and reassess the hemodynamic effects of the dose
Pediatric Dose	Administer the same regimen as in adults. Do not exceed 15 mg/dose IV Children: 0.1-0.2 mg/kg dose q2-4h prn Neonates: 0.05-0.2 mg/kg dose prn
Contraindications	Avoid use in patients with documented hypersensitivity to morphine and those diagnosed with hypotension or a potentially compromised airway where establishing rapid airway control would be difficult.
Interactions	Phenothiazines may antagonize the analgesic effects of morphine and other opiate agonists.
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Should be used with caution in patients with unstable blood pressure. May cause hypotension and respiratory depression. It is rapidly reversible with naloxone.

Drug Category: Diuretics - These are used to decrease plasma volume and edema by causing diuresis. The reduction in plasma volume and stroke volume associated with a diuresis decreases cardiac output and, consequently, blood pressure.

The initial drop in cardiac output produced by the diuresis causes a compensatory increase in peripheral vascular resistance. With continuing diuretic therapy, the extracellular fluid volume and plasma volume return almost to pretreatment levels, and peripheral vascular resistance falls below its pretreatment baseline.

Drug Name	Furosemide - It inhibits the reabsorption of sodium and chloride in the ascending loop of Henle and distal renal tubule. This interferes with the chloride-binding cotransport system, causing increased excretion of water, sodium, chloride, magnesium, and calcium.
Adult Dose	IM, IV: 40-80 mg/d
Pediatric Dose	IV or IM: 1 mg/kg slowly under close supervision. Do not exceed 6 mg/kg
Contraindications	Avoid use in patients with documented hypersensitivity to this drug, sulfonylureas, or related products and those diagnosed with anuria, hepatic coma, or in states of severe electrolyte depletion until the condition is improved or corrected.
Interactions	Metformin decreases furosemide concentrations. Conversely, furosemide interferes with the hypoglycemic effect of antidiabetic agents and antagonizes the muscle relaxing effect of tubocurarine. Auditory toxicity appears to be increased with concurrent use aminoglycosides and furosemide. Hearing loss of varying degrees may occur. The anticoagulant activity of warfarin may be enhanced, when taken concurrently with this medication. Increased plasma lithium levels and toxicity are possible when taken concurrently with this medication.
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Observe for blood dyscrasias, liver or kidney damage or idiosyncratic reactions. Perform frequent serum electrolyte, CO 2 , glucose, uric acid, calcium, creatinine, and BUN determinations during the first few months of therapy and periodically thereafter. Loop diuretics may increase the urinary excretion of magnesium and calcium.

FOLLOW-UP

Further Inpatient Care:

All patients require admission to an intensive care setting. This may occur in the form of emergent transfer to the cardiac catheterization suite, critical care transport to a tertiary care center or internal transfer to the ICU.

Transfer:

These patients are, by definition, in shock and unstable. Any attempts at transfer must be predicated on the assumption that everything possible has been done to make them as stable as possible, that there is no significant decline in the level of care during the transfer, and that the reasons for transfer are based upon the ability of the patient to receive some higher level of care at the designated transfer location.

Deterrence/Prevention:

Although cardiogenic shock is not entirely preventable, there are certainly things that can be done to minimize its risk of occurrence, recognize it at earlier stages and begin corrective therapy more expeditiously. It requires a high degree of suspicion and a heightened level of awareness.

Complications:

Cardiopulmonary arrest

Dysrhythmia

Renal failure

Multisystem organ failure

Ventricular aneurysm

Thromboembolic sequelae

Stroke

Deat

Prognosis:

Even in the best of hands, the prognosis is universally poor.

The mortality is over 70% in patients treated medically and at best, 30-50% in those achieving surgical reperfusion.

Patient Education:

Patients should be educated regarding the early warning signs of AMI and how to access EMS (911).

Patients also must be educated regarding cardiac risk factors, particularly those that are reversible and subject to volitional change (e.g., smoking, diet, and exercise).

MISCELLANEOUS

Medical/Legal Pitfalls:

Failure to recognize cardiogenic shock in the earlier stages before severe decompensation has already occurred.

Failure to obtain early consultation with a cardiologist.

Failure to focus on revascularization resulting in an undue delay in achieving reperfusion.

Failure to give sufficient volume (RV infarct without evidence of pulmonary edema).

Failure to consider other potentially reversible or contributory causes of shock (valvular dysfunction, tamponade).

Failure to adequately resuscitate patient prior to transfer.

Failure to have appropriately trained team transporting the patient.

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