BAGAS - PBL 3

A. Klarifikasi Istilah

1. Akral dingin

Suhu tubuh ekstremitas yang dibawah suhu normal (Guyton, 2006).

B. Batasan Masalah

1. Identitas pasien

a. Jenis kelamin : laki-laki

b. Usia : 58 tahun

c. Jenis pasien : rujukan

2. Keluhan utama saat ini : panas tinggi, mual, muntah

3. Keluhan sebelumnya : lemas, tak nafsu makan

4. Onset : 1 minggu

5. Faktor peringan : tidur dengan posisi setengah duduk (Posisi

Fowler)

6. Keluhan lain : mual tanpa muntah, nafsu makan berkurang

separuhnya, batuk tidak berdahak, demam (-),

terkadang sesak, keterbatasan aktivitas sehari-

hari

7. Riwayat penyakit : diabetes mellitus (sejak 5 tahun yang lalu,

rutin berobat), penyakit jantung coroner

8. Pemeriksaan fisik

a. Keadaan umum : tampak lemah dan gelisah

b. Denyut nadi : teraba lemah

c. Ekstremitas : akral teraba dingin

C. Analisis Masalah

1. Patofisiologi demam

Demam berawal dari adanya pirogen di dalam tubuh. Pirogen

merupakan agen yang menyebabkan demam. Pirogen dapat berasal dari luar

tubuh atau disebut sebagai pirogen eksogen misalnya toksin bakteri dan

mikroba lain, ada juga yang berasal dari dalam tubuh atau disebut sebagai

pirogen endogen misalnya mediator interleukin-1 (IL-1), IL-6, dan TNF.

Pirogen yang dilepaskan di dalam sirkulasi darah menyebabkan sel endothel

di kapiler hypothalamus melepaskan metabolit asam arakidonat (Prewitt,

2005).

Asam arakidonat akan dimetabolisme sebagai Prostaglandin E2

(PGE2) yang dapat melewati sawar darah otak dan menuju ke area

termoregulasi di hypothalamus. Hal ini memicu peningkatan thermal set point

menjadi titik suhu tubuh yang baru. Maka akan terjadi tiga fase demam yaitu

(Prewitt, 2005):

a. Fase inisiasi

Tubuh berusaha mencapai thermal set point yang baru dengan cara

vasokonstriksi, kontraksi otot polos m. erector pylorus, dan menggigil

yang bertujuan menjaga panas tubuh tidak keluar dan memproduksi panas

tubuh (Prewitt, 2005).

b. Fase plateau

Tubuh berhasil mencapai suhu tubuh yang baru sehingga proses

menggigil berhenti (Prewitt, 2005).

c. Fase devervescence

Tubuh membuang panas tubuh dengan cara vasodilatasi sehingga kulit

terlihat kemerahan (flushing), peningkatan sekresi keringat (diaphoresis),

dan merasa hangat (Prewitt, 2005).

2. Patofisiologi batuk

Terdapat dua reseptor yaitu yang sensitif terhadap benda asing (carina

dan laring) serta yang sensitif terhadap iritan dan korosif (bronkiolus

terminalis dan alveolus). Keduanya akan mengirimkan impuls nervus afferent

(mayoritas nervus vagus) menuju medulla oblongata dan dilanjutkan melalui

sirkuit saraf. Kemudian akan dikirimkan melalui nervus efferent menuju

organ efektor dan menghasilkan urutan efek seperti berikut (Guyton, 2006):

a. inspirasi udara 2,5 L secara cepat

b. penutupan epiglottis dan plica vocalis untuk menjebak udara dalam pulmo

c. kontraksi musculus abdominalis untuk mendorong diafragma ke atas yang

dibantu kontraksi m. intercostalis internus yang menyebabkan tekanan

intrapulmoner meningkat hingga 860 mmHg

d. secara tiba-tiba plica vocalis dan epiglottis membuka dengan lebar

e. udara keluar dari pulmo secara cepat dengan kecepatan 75-100 mil/jam

f. gerakan udara yang cepat akan membawa zat asing dan iritan keluar

sehingga tujuan refleks batuk tercapai.

DAFTAR PUSTAKA

Guyton AC, Hall JE. 2006. Textbook of Medical Pysiology 11th Edition. Philadelphia: Elsevier Saunders.

Prewitt EM. 2005. Fever: Facts, Fiction, Physiology. Crit Care Nurse Suppl: 8-10,

12, 14.

Approach ConsiderationsCardiogenic shock is an emergency requiring immediate resuscitative therapy before shock irreversibly damages vital organs. The key to a good outcome in patients with cardiogenic shock is an organized approach, with rapid diagnosis and prompt initiation of pharmacologic therapy to maintain blood pressure and cardiac output.

All patients require admission to an intensive care setting, which may involve emergent transfer to the cardiac catheterization suite, critical care transport to a tertiary care center, or internal transfer to the intensive care unit (ICU).

Early and definitive restoration of coronary blood flow is the most important intervention for achieving an improved survival rate. At present, it represents standard therapy for patients with cardiogenic shock due to myocardial ischemia.

Correction of electrolyte and acid-base abnormalities, such as hypokalemia, hypomagnesemia, and acidosis, is essential in cardiogenic shock.

Cardiogenic shock may be prevented with early revascularization in patients with myocardial infarction (MI) and with required intervention in patients with structural heart disease.

ProceduresPlacement of a central line may facilitate volume resuscitation, provide vascular access for multiple infusions, and allow invasive monitoring of central venous pressure. Central venous pressure may also be used to guide fluid resuscitation.

Although not necessary for the diagnosis of cardiogenic shock, invasive monitoring with a pulmonary artery catheter may be helpful in guiding fluid resuscitation in situations in which left ventricular preload is difficult to determine.

Pulmonary artery catheter pressure measurements may also be useful in prognosis. Retrospective evaluation of these measurements from the SHOCK trial demonstrated that stroke volume index (SVI) and stroke work index (SWI) vary inversely with mortality.[10]

An arterial line may be placed to provide continuous blood pressure monitoring. This is particularly useful if the patient requires inotropic medications.

An intra-aortic balloon pump may be placed in the emergency department as a bridge to percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG), to decrease myocardial workload and to improve end-organ perfusion.

PCI and coronary artery bypassClinicians should be alert to the fact that the SHOCK trial demonstrated that either PCI or coronary artery bypass is the treatment of choice for cardiogenic shock and that each has been shown to markedly decrease mortality rates at 1 year. PCI should be initiated within 90 minutes of presentation; however, it remains helpful, as an acute intervention, within 12 hours of presentation.

If such a facility is not immediately available, thrombolytics should be considered. However, this treatment is second best. An increased mortality is seen in situations in which thrombolytics are used instead of PCI. This is due to the relative ineffectiveness of the thrombolytic medications to lyse clots in low-blood pressure situations.[11, 1]

Consultations

Consult a cardiologist at the earliest opportunity because his or her insight and expertise may be invaluable for facilitating echocardiographic support, placement of an intra-aortic balloon pump (IABP), and transfer to more definitive care (eg, cardiac catheterization suite, ICU, operating room). In severe cases, also consider discussing the case with a cardiothoracic surgeon.

Deterrence and preventionAlthough cardiogenic shock is not entirely preventable, measures can be taken to minimize the risk of occurrence, recognize it at earlier stages, and begin corrective therapy more expeditiously. Deterrence and prevention require a high degree of suspicion and heightened awareness.

Care is required in treating patients with acute coronary syndromes who are not yet in cardiogenic shock. Careful use of beta blockers and ACE inhibitors in these patients is essential to avoid hypotension leading to cardiogenic shock.[1]

Prehospital CarePrehospital care is aimed at minimizing any further ischemia and shock. All patients require intravenous access, high-flow oxygen administered by mask, and cardiac monitoring.

Twelve-lead electrocardiography performed in the field by appropriately trained paramedics may be useful in decreasing door-to-PCI times and/or time to the administration of thrombolytics because acute ST-segment elevation myocardial infarctions (STEMIs) can be identified earlier. The emergency department (ED) can thus be alerted and may mobilize the appropriate resources.

Inotropic medications should be considered in systems with appropriately trained paramedical personnel.

When clinically necessary, positive pressure ventilation and endotracheal intubation should be performed. Continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) support can be considered in appropriately equipped systems.

Resuscitation, Ventilation, and Pharmacologic InterventionInitial management includes fluid resuscitation to correct hypovolemia and hypotension, unless pulmonary edema is present. Central venous and arterial lines are often required. Swan-Ganz catheterization and continuous percutaneous oximetry are routine.

Oxygenation and airway protection are critical; intubation and mechanical ventilation are commonly required. However, although positive pressure ventilation may improve oxygenation, it may also compromise venous return, preload, to the heart. In any event, the patient should be treated with high-flow oxygen. Studies in patients with acute cardiogenic pulmonary edema have shown noninvasive ventilation to improve hemodynamics and reduce the intubation rate. Mortality is, however, unaffected.

A study by Shin et al suggested that patients who receive extracorporeal cardiopulmonary resuscitation (CPR) versus conventional CPR for longer than 10 minutes following in-hospital arrest have a greater chance of survival.[12]

All patients with cardiogenic shock require close hemodynamic monitoring, volume support to ensure adequate sufficient preload, and ventilatory support.

Pharmacologic therapy

Patients with myocardial infarction (MI) or acute coronary syndrome are given aspirin and heparin. Both of these medications have been shown to be effective in reducing mortality in separate studies. Before initiating therapy, however, care should be taken to ensure that the patient does not have a myocardial wall rupture that is amenable to surgery.

There is no need to start clopidogrel until after angiography, since angiography may demonstrate that there is a need for urgent coronary bypass.[1]

The glycoprotein IIb/IIIa inhibitors improve the outcome of patients with non–ST-segment elevation acute coronary syndrome (NSTACS). They have been found to reduce recurrent MI following percutaneous coronary intervention (PCI) and in cardiogenic shock.

Hemodynamic SupportDopamine, norepinephrine, and epinephrine are vasoconstricting drugs that help to maintain adequate blood pressure during life-threatening hypotension and help to preserve perfusion pressure for optimizing flow in various organs. The mean blood pressure required for adequate splanchnic and renal perfusion (mean arterial pressure [MAP] of 60 or 65 mm Hg) is based on clinical indices of organ function.

In patients with inadequate tissue perfusion and adequate intravascular volume, initiation of inotropic and/or vasopressor drug therapy may be necessary. Dopamine increases myocardial contractility and supports the blood pressure; however, it may increase myocardial oxygen demand. Dobutamine may be preferable if the systolic blood pressure is higher than 80 mm Hg; it has the advantage of not affecting myocardial oxygen demand as much as dopamine does. However, the resulting tachycardia may preclude the use of this inotropic agent in some patients.

Dopamine is usually initiated at a rate of 5-10 mcg/kg/min intravenously, and the infusion rate is adjusted according to the blood pressure and other hemodynamic parameters. Often, patients may require high doses of dopamine (as much as 20 mcg/kg/min).

If the patient remains hypotensive despite moderate doses of dopamine, a direct vasoconstrictor (eg, norepinephrine) should be started at a dose of 0.5 mcg/kg/min and titrated to maintain an MAP of 60 mm Hg. The potent vasoconstrictors (eg, norepinephrine) have traditionally been avoided because of their adverse effects on cardiac output and renal perfusion.

Vasopressor supportive therapyThe following is a brief review of the mechanism of action and indications for drugs used for hemodynamic support of cardiogenic shock.[13, 14]

Dopamine

Dopamine is a precursor of norepinephrine and epinephrine and has varying effects according to the doses infused. A dose of less than 5 mcg/kg/min causes vasodilation of renal, mesenteric, and coronary beds. At a dose of 5-10 mcg/kg/min, beta1-adrenergic effects induce an increase in cardiac contractility and heart rate.

At doses of approximately 10 mcg/kg/min, alpha-adrenergic effects lead to arterial vasoconstriction and an elevation in blood pressure. The blood pressure increases primarily as a result of the inotropic effect. The undesirable effects are tachycardia and increased pulmonary shunting, as well as the potential for decreased splanchnic perfusion and increased pulmonary arterial wedge pressure.

Norepinephrine

Norepinephrine is a potent alpha-adrenergic agonist with minimal beta-adrenergic agonist effects. Norepinephrine can increase blood pressure successfully in patients who remain hypotensive following dopamine. The dose of norepinephrine may vary from 0.2-1.5 mcg/kg/min, and large doses, as high as 3.3 mcg/kg/min, have been used because of the alpha-receptor down-regulation in persons with sepsis.

Epinephrine

Epinephrine can increase the MAP by increasing the cardiac index and stroke volume, as well as systemic vascular resistance (SVR) and heart rate. Epinephrine decreases the splanchnic blood flow and may increase oxygen delivery and consumption.

Administration of this agent is associated with an increase in systemic and regional lactate concentrations. The use of epinephrine is recommended only in patients who are unresponsive to traditional agents. The undesirable effects are an increase in lactate concentration, a potential to produce myocardial ischemia, the development of arrhythmias, and a reduction in splanchnic flow.

Levosimendan

Levosimendan, though not approved for use in the United States, can be considered for use in conjunction with vasopressors. It should be used with caution, however, as it can cause hypotension. Used with vasopressors, levosimendan may improve hemodynamics and improve coronary blood flow.[15, 16]

Inotropic supportive therapyDobutamine

Dobutamine (sympathomimetic agent) is a beta1-receptor agonist, although it has some beta2-receptor and minimal alpha-receptor activity. Intravenous dobutamine induces significant positive inotropic effects, with mild chronotropic effects. It also induces mild peripheral vasodilation (decrease in afterload). The combined effect of increased inotropy and decreased afterload induces a significant increase in cardiac output.

In the setting of acute myocardial infarction (MI), dobutamine use could increase the size of the infarct because of the increase in myocardial oxygen consumption that may ensue. In general, avoid dobutamine in patients with moderate or severe hypotension (eg, systolic blood pressure < 80 mm Hg) because of the peripheral vasodilation.

Phosphodiesterase inhibitors

Phosphodiesterase inhibitors (PDIs), which include inamrinone (formerly amrinone) and milrinone, are inotropic agents with vasodilating properties and long half-lives. The hemodynamic properties of PDIs are (1) a positive inotropic effect on the myocardium and peripheral vasodilation (decreased afterload) and (2) a reduction in pulmonary vascular resistance (decreased preload).

PDIs are beneficial in persons with cardiac pump failure, but they may require concomitant vasopressor administration. Unlike catecholamine inotropes, these drugs are not dependent on adrenoreceptor activity; therefore, patients are less likely to develop tolerance to these medications.

PDIs are less likely than catecholamines to cause adverse effects known to be associated with adrenoreceptor activity (eg, increased myocardial oxygen demand, myocardial ischemia). They are also associated with less tachycardia and myocardial oxygen

consumption. However, the incidence of tachyarrhythmias is greater with PDIs than with dobutamine.

Thrombolytic TherapyAlthough thrombolytic therapy (TT) reduces mortality rates in patients with acute myocardial infarction (MI), its benefits for patients with cardiogenic shock secondary to MI are disappointing. When used early in the course of MI, TT reduces the likelihood of subsequent development of cardiogenic shock after the initial event.

In the Gruppo Italiano Per lo Studio Della Streptokinase Nell'Infarto Miocardio trial, 30-day mortality rates were 69.9% in patients with cardiogenic shock who received streptokinase, compared to 70.1% in patients who received a placebo.

Similarly, other studies employing a tissue plasminogen activator did not show reductions in mortality rates from cardiogenic shock. Lower rates of reperfusion of the infarct-related artery in patients with cardiogenic shock may help to explain the disappointing results from TT. Other reasons for the decreased efficacy of TT are the existence of hemodynamic, mechanical, and metabolic causes of cardiogenic shock that are unaffected by TT.

Thrombolytic therapy plus IABPA prospective cohort study demonstrated the potential survival benefit of combining TT with IABP counterpulsation in patients with MI complicated by cardiogenic shock. [17]

Out of 1190 patients enrolled, the treatments were (1) no TT and no IABP counterpulsation (33%, n = 285), (2) IABP counterpulsation only (33%, n = 279), (3) TT only (15%, n = 132), and (4) TT and IABP counterpulsation (19%, n = 160).

Patients in cardiogenic shock who were treated with TT had lower in-hospital mortality rates than did those who did not receive TT (54% vs 64%), and patients selected for IABP counterpulsation had lower in-hospital mortality rates than did those who did not receive IABP counterpulsation (50% vs 72%).

Furthermore, a significant difference was noted in inhospital mortality rates among the 4 treatment groups; ie, TT plus IABP counterpulsation (47%), IABP counterpulsation only (52%), TT only (63%), no TT and no IABP counterpulsation (77%).

Revascularization influenced in-hospital mortality rates significantly (39% with revascularization vs 78% without revascularization).

Patients who are unsuitable for invasive therapy should be treated with a thrombolytic agent in the absence of contraindications. This is a class I recommendation by American College of Cardiology (ACC)/American Heart Association (AHA) guidelines.

Intra-Aortic Balloon PumpThe use of the IABP reduces systolic left ventricular afterload and augments diastolic coronary perfusion pressure, thereby increasing cardiac output and improving coronary artery blood flow. The IABP is effective for the initial stabilization of patients with cardiogenic shock. However, an IABP is not definitive therapy; the IABP stabilizes patients so that definitive diagnostic and therapeutic interventions can be performed.[18, 19]

The IABP also may be a useful adjunct to thrombolysis for initial stabilization and transfer of patients to a tertiary care facility. Some studies have shown lower mortality rates in patients with myocardial infarction (MI) and cardiogenic shock treated with an IABP and subsequent revascularization, as previously mentioned.

Complications may be documented in up to 30% of patients who undergo IABP therapy; these relate primarily to local vascular problems, embolism, infection, and hemolysis.

The impact of treatment with an IABP on long-term survival is controversial and depends on the patient’s hemodynamic status and the etiology of the cardiogenic shock. Patient selection is the key issue; inserting the IABP early, rather than waiting until full-blown cardiogenic shock has developed, may result in clinical benefit.

Ramanathan et al found that rapid and complete reversal of systemic hypoperfusion with IABP counterpulsation in the SHOCK trial and SHOCK registry was independently associated with improved inhospital, 30-day, and 1-year survival, regardless of early revascularization. This suggests that complete reversal of systemic hypoperfusion with IABP counterpulsation is an important early prognostic feature.[20]

In the IABP-SHOCK II study, 600 patients with cardiogenic shock complicating acute myocardial infarction were randomized to intraaortic balloon counterpulsation or no intraaortic balloon counterpulsation. All patients were expected to undergo early revascularization. Use of intraaortic balloon counterpulsation did not significantly reduce 30-day mortality in these patients.[21]

Ventricular Assist DevicesIn recent years, left ventricular assist devices (LVADs) capable of providing complete short-term hemodynamic support have been developed. The application of LVAD during reperfusion, after acute coronary occlusion, causes reduction of the left ventricular preload, increases regional myocardial blood flow and lactate extraction, and improves general cardiac function. The LVAD makes it possible to maintain the collateral blood flow as a result of maintaining the cardiac output and aortic pressure, keeping wall tension low and reducing the extent of microvascular reperfusion injury.[18, 19, 22]

A pooled analysis from 17 studies showed that the mean age of this group of patients with LVADs was 59.5 ± 4.5 years and that mean support duration was 146.2 ± 60.2 hours. In 78.5% of patients (range, 53.8-100%), adjunctive reperfusion therapy, mainly percutaneous transluminal coronary angioplasty (PTCA), was used. Mean weaning and survival rates were 58.5% (range, 46-75%) and 40% (range, 29-58%), respectively. [18]

In any case, comparing studies is difficult because important data are usually missing, mean age of patients were different, and time to treatment is not standardized. Hemodynamic presentation seems to be worse compared with data reported in the SHOCK trial, with lower cardiac index, lower systolic aortic pressure, and higher serum lactates. Taking these considerations into account, LVAD support seems to give no survival improvement in patients with cardiogenic shock complicating acute myocardial infarction (MI), compared with early reperfusion alone or in combination with IABP.

In a randomized, controlled trial in which 129 patients with end-stage heart failure who were ineligible for cardiac transplantation were assigned either to receive an LVAD (68 patients) or to undergo optimal medical management, survival rates were higher in the LVAD group. The rates of survival at 1 year were 52% in the device group and 25% in the medical therapy group, while the rates at 2 years were 23% and 8%, respectively. In addition, the quality of life was significantly improved at 1 year in the device group.[23]

Implantable LVADs are being used as a bridge to heart transplantation for patients with acute MI and cardiogenic shock.[24] According to the HeartMate Data Registry[25] , from 1986-1998, 41 patients (5% of the total number of HeartMate IP patients) were supported with this implantable pneumatic device for acute MI, and 25 (61%) were successfully bridged to heart transplantation.

However, LVADs as a bridging option for patients with cardiogenic shock must be considered cautiously and must be avoided in patients who are unlikely to survive or are not likely to be transplant candidates. Further investigations are required to better define indications, support modalities, and outcomes.

The indications for insertion of a ventricular assist device are controversial. Such an aggressive approach to support the circulatory system in cardiogenic shock is appropriate (1) after the failure of medical treatment and an IABP, (2) when the cause of cardiogenic shock is potentially reversible, or (3) if the device can be used as a bridging option.

Percutaneous Transluminal Coronary AngioplastyThe retrospective and prospective data favor aggressive mechanical revascularization in patients with cardiogenic shock secondary to myocardial infarction (MI).

Reestablishing blood flow in the infarct-related artery may improve left ventricular function and survival following MI. In acute MI, studies show that percutaneous transluminal coronary angioplasty (PTCA) can achieve adequate flow in 80-90% of patients, compared with 50-60% of patients after thrombolytic therapy (TT).

Several retrospective clinical trials have shown that patients with cardiogenic shock due to myocardial ischemia benefitted (reduction in 30d mortality rates) when treated with angioplasty. A study of direct (primary) PTCA in patients with cardiogenic shock reported lower mortality rates in patients treated with angioplasty combined with the use of stents than in patients treat with medical therapy.

A study by Antoniucci et al found that mortality rates increase in relation to the length of time to treatment in patients with acute MI who are not considered to be at low risk. To study the relationship of time to treatment and mortality in patients with acute MI, a series of 1336 patients who underwent successful primary PTCA were stratified into low-risk and not ̶ low risk patient groups. The 6-month mortality rate was 9.3% for not–low risk patients and 1.3% for the low-risk patients. An increase in the mortality rate from 4.8% to 12.9% with increasing time to reperfusion was observed in the not low–risk group. A delay from symptom onset to treatment resulted in higher mortality rates for the not low–risk patients. [26]

Coronary Artery Bypass GraftingCritical left main artery disease and 3-vessel coronary artery disease are common findings in patients who develop cardiogenic shock. The potential contribution of ischemia in the noninfarcted zone contributes to the deterioration of already compromised myocardial function.

Coronary artery bypass grafting (CABG) in the setting of cardiogenic shock is generally associated with high surgical morbidity and mortality rates. Because the results of percutaneous interventions can be favorable, routine bypass surgery is often discouraged for these patients.

A 2004 task force of the ACC and the AHA gave a class I recommendation to the performance of primary PCI or emergent CABG in patients younger than 75 years who have STEMI who develop shock within 36 hours of myocardial infarction (MI) and can be treated within 18 hours of shock onset. Performance of primary PCI or emergent CABG was considered reasonable in patients older than 75 years (class IIa recommendation).

Revascularization in the SHOCK TrialResults from the SHOCK trial supported the superiority of a strategy that combines early revascularization with medical management in patients with cardiogenic shock. In the study,

patients were assigned to receive either optimal medical management, including an IABP and TT, or cardiac catheterization followed by revascularization using PTCA or CABG.[27, 11, 28]

The mortality rates at 30 days were 46.7% in the early intervention group and 56% in patients treated with optimal medical management. Although these 30-day results did not reach statistical significance, the mortality rate at 6 months was significantly lower in the early intervention group (50.3% vs 63.1%).[27]

The 1-year survival rates were also reported from the SHOCK trial. [11] The survival rate at 1-year was 46.7% for patients in the early revascularization group and 33.6% in the conservative management group. The treatment benefit was apparent only for patients younger than 75 years (51.6% survival rate in early revascularization group vs 33.3% in patients treated with optimal medical management).

Based on the outcome of this study, the recommendation is that patients with acute myocardial infarction (MI) complicated by cardiogenic shock, particularly those younger than 75 years, should be rapidly transferred to a center with personnel capable of performing early angiography and revascularization procedures.

Patient TransferImmediately transfer a patient who develops cardiogenic shock to an institution at which invasive monitoring, coronary revascularization, and skilled personnel are available to provide expert care.

Patients with cardiogenic shock who are admitted to a hospital without facilities for revascularization should be immediately transferred to a tertiary care center with such facilities. If time to PCI is more than 1 hour and onset of symptoms has been within 3 hours, rapid administration of TT is recommended.

It should be kept in mind, however, that attempts to transfer a patient with cardiogenic shock must be made only when everything possible has been done to stabilize his or her condition and when the level of care during the transfer will not significantly decrease.

Medication SummaryVasopressors augment the coronary and cerebral blood flow during the low-flow state associated with shock. Sympathomimetic amines with both alpha- and beta-adrenergic effects are indicated for persons with cardiogenic shock. Dopamine and dobutamine are the drugs of choice to improve cardiac contractility, with dopamine the preferred agent in patients with hypotension.

Vasodilators relax vascular smooth muscle and reduce the SVR, allowing for improved forward flow, which improves cardiac output.

Diuretics are used to decrease plasma volume and peripheral edema. The reduction in extracellular fluid and plasma volume associated with diuresis may initially decrease cardiac output and, consequently, blood pressure, with a compensatory increase in peripheral vascular resistance. With continuing diuretic therapy, the plasma volume and peripheral vascular resistance usually return to pretreatment values.

Inotropic AgentsClass Summary

These agents augment coronary and cerebral blood flow during the low-flow state associated with cardiogenic shock. They also improve cardiac output in refractory hypotension and shock.

View full drug informationDopamine 

Dopamine stimulates adrenergic and dopaminergic receptors. Its hemodynamic effect depends on the dose. Lower doses primarily stimulate dopaminergic receptors that produce renal and mesenteric vasodilation. Higher doses produce cardiac stimulation and vasoconstriction.

View full drug informationDobutamine 

Dobutamine is a sympathomimetic amine with stronger beta effects than alpha effects. It produces systemic vasodilation and increases the inotropic state. Higher doses may cause an increase in heart rate, exacerbating myocardial ischemia.

View full drug informationNorepinephrine (Levophed) 

Norepinephrine is a naturally occurring catecholamine with potent alpha-receptor and mild beta-receptor activity. It stimulates beta1- and alpha-adrenergic receptors, resulting in increased cardiac muscle contractility, heart rate, and vasoconstriction. Norepinephrine increases blood pressure and afterload. Increased afterload may result in decreased cardiac output, increased myocardial oxygen demand, and cardiac ischemia.

Norepinephrine is generally reserved for use in patients with severe hypotension (eg, systolic blood pressure < 70 mm Hg) or hypotension unresponsive to other medication.

View full drug informationMilrinone 

Milrinone is a selective phosphodiesterase inhibitor in cardiac and vascular tissue with positive inotropic and vasodilator effects; it has little chronotropic activity. This agent's mode of action differs from that of either digitalis glycosides or catecholamines.

View full drug informationInamrinone 

Formerly known as amrinone, inamrinone is a phosphodiesterase inhibitor with positive inotropic and vasodilator activity. It produces vasodilation and increases the inotropic state. Inamrinone is more likely to cause tachycardia than is dobutamine, and it may exacerbate myocardial ischemia.

VasodilatorsClass SummaryVasodilators decrease preload and/or afterload.

View full drug informationNitroglycerin IV 

This agent causes relaxation of vascular smooth muscle by stimulating intracellular cyclic guanosine monophosphate production. The result is a decrease in preload and blood pressure (ie, afterload).

Antiplatelet Agents, CardiovascularClass SummaryAgents that irreversibly inhibit platelet aggregation may improve morbidity.

View full drug informationAspirin (Anacin, Ascriptin Regular Strength, Bayer Aspirin Regimen Regular, Bufferin, Ecotrin) 

Aspirin is an odorless, white, powdery substance available in 81 mg, 325 mg, and 500 mg, for oral use. When exposed to moisture, aspirin hydrolyzes into salicylic acid and acetic acids. It is a stronger inhibitor of prostaglandin synthesis and platelet aggregation than are other salicylic acid derivatives. The acetyl group is responsible for inactivation of cyclo-oxygenase via acetylation. Aspirin is hydrolyzed rapidly in plasma, and elimination follows zero order pharmacokinetics.

Aspirin irreversibly inhibits platelet aggregation by inhibiting platelet cyclo-oxygenase. This, in turn, inhibits the conversion of arachidonic acid to prostaglandin 12 (a potent vasodilator and inhibitor of platelet activation) and thromboxane A2 (a potent vasoconstrictor and platelet aggregate). Platelet-inhibition lasts for the life of the cell (approximately 10 d).

Aspirin may be used at a low dose to inhibit platelet aggregation and improve complications of venous stases and thrombosis. It reduces the likelihood of myocardial infarction (MI) and is also very effective in reducing the risk of stroke. Early administration of aspirin in patients with acute MI may reduce cardiac mortality in the first month.

Opioid AnalgesicsClass SummaryAnalgesics reduce pain, which decreases sympathetic stress and provides some preload reduction.

View full drug informationMorphine sulfate (Duramorph, Astramorph, MS Contin, Kadian, Oramorph SR) 

Morphine sulfate is the drug of choice for narcotic analgesia due to its reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Various intravenous doses are used; the drug is commonly titrated until the desired effect is achieved.

Diuretics, LoopClass SummaryThese drugs cause diuresis to decrease plasma volume and edema and thereby decrease cardiac output and, consequently, blood pressure. The initial decrease in cardiac output causes a compensatory increase in peripheral vascular resistance. With continuing diuretic therapy, extracellular fluid and plasma volumes return almost to pretreatment levels. Peripheral vascular resistance decreases below that of the pretreatment baseline.

View full drug informationFurosemide (Lasix) 

Furosemide increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and the distal renal tubule.

Individualize the dose to the patient. Depending on the response, administer furosemide at increments of 20-40mg no sooner than 6-8 hours after the previous dose, until the desired diuresis occurs. When treating infants, titrate the drug in increments of 1mg/kg/dose until a satisfactory effect is achieved.

Cardiovascular, OtherClass SummaryThese drugs cause arterial and venous dilation by binding to the cyclic guanosine monophosphate (GMP) receptors on vascular smooth muscle, causing smooth muscle relaxation. Natriuretic peptides produce dose-dependent decreases in pulmonary capillary wedge pressure and systemic arterial pressure.

View full drug informationNesiritide (Natrecor) 

Nesiritide is a recombinant deoxyribonucleic acid (DNA) form of human B-type natriuretic peptide (hBNP), which dilates veins and arteries.

Human BNP binds to the particulate guanylate cyclase receptor of vascular smooth muscle and endothelial cells. Binding to the receptor causes an increase in cyclic GMP, which serves as a second messenger to dilate veins and arteries. Pulmonary capillary wedge pressure is reduced and dyspnea is improved in patients with acutely decompensated congestive heart failure.

Nesiritide may be considered in the treatment of patients with cardiogenic shock. Although nesiritide has been shown to increase mortality and renal dysfunction, it continues to be studied as a treatment for acute congestive heart failure and currently retains US Food and Drug Administration (FDA) approval. However, it should be used with caution in the setting of cardiogenic shock because it has been shown to cause hypotension.