Cardiogenic shock (CS), a state of tissue hypoperfusion secondary to inadequate cardiac output (CO), presents many challenges in both the pre-hospital and hospital setting. Despite many advances in both the medical and mechanical management of CS, the mortality remains relatively high at approximately 50%. (6) We aim to review the current state of evidence pertaining to the medical management in the critical care transport environment.
What is it?
The definition of CS has evolved over the years. A commonly used definition, adopted by the SHOCK trial (Table 1), is defined by the presence of three objective factors. (3) While this binary definition is necessary for research, clinically the definition of CS continues to evolve as it encompasses a continuum of disease. The CS continuum begins with decreased stroke volume, which can be due to a myriad of etiologies though most typically is caused by ischemia. Vital sign derangements should not be considered an absolute prerequisite prior to inclusion on the CS continuum. The continuum of disease encompasses patients with subtle hemodynamic alterations as well as those with complete cardiovascular collapse. In the initial stages of CS the patient may remain normotensive as a result of vasoconstriction; however any point along this continuum is subject to acute changes that require quick recognition and swift escalation of therapy. It should be noted that all patients on this continuum are susceptible to end organ failure, even if not secondary to overt ischemia.
“Heart failure” and “cardiogenic shock” do not refer to just one entity. Further classification is according to:
Portion of the cardiac cycle (systole/diastole)
Side of the heart (right/left)
While there are many recognized causes of cardiogenic shock, both ischemic and non-ischemic (Table 2), we will discuss the common causes which may alter the destination or medical management. Acute coronary syndrome is the most common cause of CS. In the CardShock study (7) ST-segment myocardial infarction (STEMI) was the identified cause in 68% of the patients, while the SHOCK trial registry (3) found myocardial ischemia to account for almost 78% of patients in acute CS. While non-ischemic causes are far less common, it is important to thoroughly consider all causes especially with nonspecific findings on EKG. Cardiac arrhythmias can also be a significant contributing cause of CS.
How to recognize Cardiogenic Shock:
The classic features of shock include clinical evidence of hypoperfusion such as altered mental status, hypotension, oliguria, and evidence of metabolic acidosis on laboratory evaluation. This will likely be seen in patients experiencing CS in addition to signs more specific, but not exclusive to, CS such as elevated JVP, coolness of the skin, and narrow pulse pressure. The "classic" patient with cardiogenic shock secondary to left ventricular dysfunction has severe systemic hypotension, signs of systemic hypoperfusion, and respiratory distress due to pulmonary congestion. Whereas, isolated right ventricular function will not have pulmonary congestion. Of note, in the SHOCK trial registry 5.2 percent did not have overt hypotension (SBP< 90 mmHg) despite signs of peripheral hypoperfusion (oliguria, cold extremities, or both). (4)
Interpretation of PAC Numbers: (8, 9)
As a critical care transport provider, you may find yourself transporting a patient out of a cath lab or ICU with a pulmonary artery catheter (Swan-Ganz catheter) and an understanding of what these numbers mean can help guide your therapy. The pulmonary artery catheter (PAC) has a balloon that when inflated allows venous blood to carry it through the right side of the heart and into the pulmonary arteries. It is a 7F catheter with two internal channels (distal/PA lumen and 30 cm proximal to the catheter tip-proximal or RA lumen). The tip of the catheter has a 1.5 ml balloon. The PAC is inserted through an 8 or 9F introducer (think your Cordis catheters) that is usually in the subclavian or IJ vein, however, femoral veins can also be used. The distal lumen is attached to a pressure transducer as the catheter is advanced. The catheter is usually inserted approximately 20 cm into the SVC where you will start to see a venous waveform and the balloon is inflated. The catheter is advanced, with the balloon inflated, until the wedge pressure is noted and the balloon is deflated. The PAC is secured in place, and the distance inserted is noted. CXR is obtained to verify PAC placement.
Waveforms of the advancement of the PAC (10):
What data can you obtain from the PAC?
Let’s break it down:
Central Venous Pressure
Remember that proximal port sitting in the right atrium? The pressure in the RA is functionally the same as the pressure in the SVC and these pressures are known as the central venous pressure. In the absence of tricuspid disease, the CVP should also equal the right ventricular end diastolic pressure (CVP=RAP=RVEDP). In many cases, CVP is used as a guide for RIGHT ventricular filling pressures.
Pulmonary Artery Wedge Pressure
Remember where the balloon migrated to- the pulmonary arteries. The PAWP is used as a surrogate measure of left atrial pressure. Just as above, in the absence of mitral valve disease, the PAWP also represents the left ventricular end diastolic pressure (PAWP=LAP=LVEDP). The PAWP is used as a guide for LEFT ventricular filling pressures.
The thermodilution cardiac output (CO) is the average stroke output of the heart in one-minute periods. It is typically adjusted for the BSA and thus becomes cardiac index (CI=CO/BSA).
We have all heard of stroke volume (SV=CO/HR). Replace cardiac output (CO) in the equation with cardiac index (CI) and you have the stroke index (SI=CI/HR). The stroke index is the measure of systolic performance during one cardiac cycle.
Systemic Vascular Resistance Index
SVR is a global measure of resistance and flow. The SVR is directly related to the pressure drop from the aorta to the RA and inversely related to CI [SVRI=(MAP-CVP)/CI]. Wood units was used in this example but multiply your number by 80 and you will find more conventional SVR numbers (800 – 1200 dynes ∙ sec/cm5).
Pulmonary Vascular Resistance Index
Just as the SVR, the PVR is a global measurement and is representative of the pressure drop from the pulmonary artery to the left atrium, divided by CI. [PVRI=(PAP-PAWP)/CI] Again, multiply by 80 if you want the more conventional units.
Oxygen Transport Parameters
These provide a global measure of oxygen supply and consumption. The rate of oxygen transport in arterial blood is the oxygen delivery (DO2) and is the product of CI and oxygen concentration in arterial blood (DO2=CIxCaO2). CaO2 is based on several factors including hemoglobin concentration and percent of hemoglobin bound to oxygen.
Oxygen uptake or consumption (VO2) is the rate at which oxygen is taken up from the capillaries into the tissues. VO2 is the difference between arterial and venous concentrations (VO2=CaO2-CvO2). The O2ER is the measure of balance between oxygen delivery and uptake. If normally is approximately 25%, this means that 25% of the oxygen delivered to the capillaries is taken up into the tissues.
Progression of Heart Failure
The earliest sign of left ventricular dysfunction is an increase in cardiac filling pressure (PAWP). Stroke volume is maintained but at the expense of the elevated filing pressure which produces venous congestion in the lungs and the sensation of dyspnea.
The next stage is decrease in stroke volume and an increase in heart rate. The tachycardia offsets the reduction in stroke volume so the CO is preserved.
The final stage is characterized by the decrease in CO and a further increase in filling pressure. As the CO begins to fall marks the transition between compensated and decompensated heart failure.
A case to illustrate the above points:
Imagine you fly out to another hospital to pick up a patient in a combined ICU. The patient is intubated, hypotensive, grey, peripherally cold… The initial story was that this elderly patient was found down at home and came into the ED unresponsive. Little is known about their medical history. The intensivist put in a PAC. You want to use these numbers to aid in:
Determining the type of shock
Directing your treatment to the type of shock
Your outside hospital patient has a CVP of 16, CI of 1.8, and a high SVR. Let’s also say the patient also has a low VO2. Your patient is in cardiogenic shock.
When CS is suspected in the critical care transport setting the initial goals are to identify the cause while restoring cardiac output and optimizing tissue perfusion. Temporal optimization of tissue perfusion in the critical care transport setting is key to prevent end-organ failure and is often accomplished through limited fluid resuscitation, vasopressor, and inotropic administration. As a critical care transport team assumes care, the patient should be placed on defibrillator pads upon transfer to your team as these patients are susceptible to many acute changes, including arrhythmias.
An EKG should be made a priority following the basic assessment as identification of a STEMI will drastically change both disposition and management. STEMI’s resulting in CS are often not subtle, however location of the infarction should be noted. While the logistical details vary among institutions, the ultimate destination of a patient in CS secondary to a STEMI should be the cath lab for percutaneous coronary intervention (PCI). Critical care transport teams should be familiar with the logistics required to facilitate both transportation to and activation of the cath lab as PCI is critical andshould be carried out expeditiously. While the American Heart Association (AHA) recommends invasive approaches (PCI) over fibrinolytic therapy in patients with STEMI complicated by CS, they recognize timely invasive intervention is not available to all patients. (6) Therefore, although evidence is lacking fibrinolytic therapy should be considered for patients with MI complicated by CS if transport to PCI capable center is not available or delayed. Additionally, according to the American College of Cardiology (ACC) and theAHA patients with NSTEMI and hemodynamic instability also mandate emergent PCI. As in any patient with myocardial ischemia, in a patient with a STEMI and CS aspirin should be administered. (6)
Intravenous fluids can be administered in patient to optimize the cardiac filling pressure and maintain euvolemia for optimal cardiac function. As observed on the Frank-Starling curve, as volume status increases, myocytes get stretched, and the cardiac index increases. However, once the patient’s volume status reaches the flattening of the Frank-Starling curve, an increase in volume does not change the cardiac index and can worsen the patient’s clinical status. Many patients in CS, however, have a diffusely flat Frank-Starling curve. Therefore, IVF fluids should not be administered prior to a prudent pulmonary exam, and should be administered with caution as additional fluid loading can cause one to venture into unfavorable regions of the Frank-Starling curve leading to an increase in an already elevated left ventricular end diastolic pressure, worsening the CS and pulmonary edema.
Volume infusion is usually the initial approach for RCA infarct and hypotension (right sided heart failure). If volume therapy is not improving BP or if CVP and PAWP are starting to equalize (if this data is available), inotropic therapy can be initiated.
While crystalloid is currently the most common fluid administered, there is little date regarding the type of IVF to administer in CS.
Norepinephrine (NE/Levophed), epinephrine (Adrenalin), and dopamine are vasoactive medications used in the acute treatment of CS. These vasoactive medications act on alpha-1 adrenergic receptors leading to activation of inositol triphosphate mediated calcium release, smooth muscle contraction, and ultimately vasoconstriction resulting in an increased mean arterial pressure (MAP). However, these medications are not without side effects as they can also increase myocardial oxygen demand and can make conditions favorable to arrhythmias. At high doses, this can lead to tissue hypoxia, ischemia, lactic acidosis, and increased mortality. (2) The increase in left ventricular afterload, resulting from increased MAPs, can often outweigh the inotropic effect of these medications and the resultant cardiac output may be further decreased giving way to the need for additional inotropes. Therefore, while often necessary, it is the unanimous consensus that these medications should be administered at the lowest dose for the shortest period. While these medications are ideally given through a central line, remember that NE and epinephrine can be run through a large bore IV cannula in the cubital fossa if needed for a short time.
NE is frequently the first line vasopressor in CS, exhibiting its predominant effects on alpha-adrenergic receptors located within the vasculature, while having a modest but lesser effect on beta-adrenergic receptors within the heart. This results in significantly increased smooth vascular resistance (SVR) while having little effect on myocardial oxygen consumption. NE increases cardiac index and mixed venous oxygen saturation, without an increase in heart rate or lactate (5). Furthermore, the SHOCK II trial showed that NE has less arrhythmic potential and decreased mortality compared with dopamine (1).
Epinephrine has potent beta-1-adrenergic receptor activity and modest alpha-1-adrenergic and beta-2-adrenergic activity. The beta-1-adrenergic receptor activity results in significantly increased inotropic effect and increased cardiac output, while alpha-1-adrenergic and beta-2-adrenergic activity on SVR are dose-dependent. At low does beta-2-adrenergic is predominant resulting in a decreased SVR, while at higher doses alpha-1-adrenergic activity predominates and SVR increases. Epinephrine is first line in anaphylactic shock, but is not frequently the initial vasopressor in CS.
Dopamine, the endogenous precursor to NE and epinephrine, has dose-dependent effects on SVR. Low doses of dopamine cause dilation of the splanchnic and renal vascular beds. Intermediate doses affect beta-2 adrenergic receptors, increasing the heart rate and cardiac contractility. Lastly, high doses affect the alpha-adrenergic receptors leading to vasoconstriction and increasing SVR. Historically dopamine found much favorability as the vasopressor of choice for CS. However, the SOAP II trial showed increased arrhythmogenic potential and mortality compared to NE, leading many to reach for NE ahead of dopamine in their cardiogenic shock armamentarium (1). The AHA suggests that while NE may be the vasopressor of choice in many patients with CS, the optimal first-line vasoactive medication in CS remains unclear secondary to major study limitations in the SOAP II trail. (6).
Although not mentioned above, vasopressin should be mentioned as it increases preload without increasing afterload and is often considered in cardiogenic shock secondary to right heart failure. Vasopressin, a neuropeptide endogenously produced by the hypothalamus, acts on multiple receptors. However, the vasopressor effects are caused by vasopressin’s effects on V1. While vasopressin may increase cardiac perfusion through increased preload, it has little effect on myocardial oxygen demand and decreased arrythmogenic potential compared to other vasopressors. Vasopressin has been found to be safe, and to decrease NE requirements, in vasodilator shock. (12) However, in cardiogenic shock recent literature, although limited, demonstrates an increased mortality when used in combination with other vasopressors. (13)
Inotropes, dobutamine and milrinone, are critical in the acute temporal medical management of CS. These agents act by increasing adenosine monophosphate, which activates protein kinase A and increases intracellular calcium, ultimately increasing contractility. While these medications increase cardiac output through increased contractility, they unfortunately also increase myocardial oxygen consumption and the risk of arrhythmias.
Dobutamine acts on beta-1 and beta-2 adrenergic receptors. Beta-1 adrenergic activity results in increased cardiac contractility and cardiac output, while beta-2 adrenergic activity can often result in vasodilation, decreasing SVR. Therefore, while dobutamine is the most common inotrope used in CS, it is typically administered with NE, and should be considered following stabilization. Simultaneous vasopressor administration is typically required due to dobutamine induced hypotension from beta-2 adrenergic stimulation. Dobutamine alone will only increase BP when the SV increase is greater than the SVR decrease so often a vasopressor will also be required.
Milrinone, a phosphodiesterase-3 inhibitor, increases cardiac contractility through increased cyclic adenosine monophosphate levels. While there is no significant change in heart rate, milrinone can cause vasodilation, takes several hours to take effect, and must be renally adjusted. You may transport patients already initiated on milrinone and should remember that onset of action with titration of the infusion will not show immediate hemodynamic effects. As such, when initiating an inotrope in the critical care transport environment, dobutamine is usually the first choice.
A word on epinephrine: push dose epinephrine and epi continuous infusions are commonly used by emergency physicians. One 2011 study compared norepinephrine/dobutamine versus epinephrine (11). Epinephrine had similar BP effects but epinephrine was associated with a transient lactic acidosis, higher heart rate and arrhythmia, and inadequate gastric mucosa perfusion so the dobutamine/norepi combination was found to be safer. Given the side effects of epinephrine, dobutamine is typically preferred, however, if no other drug is available, epinephrine is an acceptable short-term alternative.
Hypertension and Heart Failure: (9)
Rarely, you may find yourself in the position to transport a patient that is hypertensive with signs of heart failure. The hallmark of therapy will be vasodilator therapy followed by diuresis if there is evidence of volume overload (or PAWP > 20).
Nitroglycerin- start infusion 5 mcg/min and titrate by 5 mcg/min (upwards to 100 to 200 mcg/min depending on the text you read). Goal should be to initially decrease the BP by 20-25%. Tachyphylaxis can be seen 16-24 hours after initiation.
Nitroprusside- Start the infusion at 0.1 mcg/kg/min and titrate upwards every 5 min for the desired effect. The maximum dose is 5 mcg/kg/min but this is a really high dose so not typically recommended (in fact we would not titrate above 3 mcg/kg/min). In the critical care transport environment we would caution against starting this de novo without discussion with the accepting facility. Additionally, this drug should be avoided in patients with renal failure and is contraindicated post-MI. When administering this drug, cyanide toxicity is the major concern with this medication. Lastly, if you are transporting a patient on this infusion, consider placing an arterial line prior to transport, however policies will vary among institutions.
Diuresis is recommended if signs of volume overload are present. Furosemide/torsemide are usually the first line agents, even in the setting of acute kidney injury. Diuresis may result in improved cardiac output and subsequent improvement in renal function.
In addition to medication options, you may find yourself transporting patients with mechanical assist devices. Discussing specific transport considerations for these devices is outside the scope of this talk but each will be touched on briefly to provide you an overview.
VAD Patients: Patients with a LVAD in place are usually quite knowledgeable about their device, or their family members may be able to help fill in the gaps in the event the patient is not a reliable historian. Patients with an LVAD may not have a palpable pulse as their pumps are non-pulsatile. If a patient has an LVAD, the VAD coordinator on-call should be notified of admission or problems.
Intra-aortic balloon pump: Inflation of the balloon during diastole which increases peak diastolic pressure and augments coronary artery flow. Deflation reduces pressure in the aorta and augments stroke output.
Impella: This device sits in the left ventricle across the aortic valve and augments CO through the aorta. It is placed in the cath lab.
VA ECMO: Veno-arterial (VA) extracorporeal membrane oxygenation can be considered in severe cardiogenic shock with presumed reversible cause. Occasionally a transport team may encounter a patient that may benefit from VA ECMO. A multi-disciplinary team is required for this so notifications should be made early. The ECMO team is available to transport patients already cannulated at outside hospitals.
Consider possible VA ECMO in patients with:
Cardiogenic shock patients with evidence of inadequate tissue perfusion* despite :
Adequate intravascular volume administration
2 moderate/1 high dose inotropes/vasoconstrictor +/- IABP or Impella for LV failure
2 moderate/1 high dose inotropes with a pulmonary vasodilator+/-IABP or Impella for RV failure
*Indicators of inadequate tissue perfusion
CI < 2
SVO2 < 60%
MAP < 65mmHg
Lactate > 2
UOP < 0.5ml/kg/hr X 2 hours
Cool, mottled extremities
Despite the many challenges CS presents in the critical care transport, it must be recognized and treated in an expedient manner
An EKG driven final destination must be quickly determined for expedient PCI, if necessary
CardShock study (7) ST-segment myocardial infarction (STEMI) was the identified cause in 68% of the patients, while the SHOCK trial registry (3) found myocardial ischemia to account for almost 78% of patients in acute CS
Temporal optimization of cardiac output and tissue perfusion through limited fluid resuscitation, vasopressor, and inotropic administration is required to delay the CS continuum and prevent end-organ failure
NE and epinephrine can be run through a large bore IV cannula in the cubital fossa if need
SOAP II trial favors NE administration in the tachycardic CS patient or those prone to arrhythmias
Dopamine remains first-line for the bradycardic CS patient
Dobutamine is often the preferred inotrope as it has an immediate effect and does not require renal dosing.
Concomitant vasopressor administration is often required secondary to the hypotension caused by dobutamine
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