Michael D Schmidt, PharmD Critical Care Clinical Pharmacist Belleville Memorial Hospital Belleville, IL

I have no conflicts of interest to disclose

1. Understand hemodynamic variables used to classify shock syndromes 2. Classify 4 different types of shock based on etiology 3. Compare vasoactive drugs commonly used to treat shock 4. Develop a treatment plan for a patient presenting with shock

What is shock? – Inadequate perfusion – Leading to inadequate oxygen delivery Is it hypotension? – Commonly – Be aware of patient specific variables

Altered Mental Status – Anywhere from confusion to coma Skin findings – Cool/Cold – Clammy – Poor turgor Renal function – Low urine output – Elevated creatinine?

Mean Arterial Pressure (MAP) mmHg – An estimation of peripheral arterial blood flow – Essential for tissue/organ perfusion Heart Rate (HR) BPM – The rate at which the heart is beating SBP + (2 x DBP) MAP = 3

Cardiac Output (CO) L/min – A measure of the amount of blood being pumped by the heart CO = SV x HR Systemic Vascular Resistance (SVR) – Measures constriction/dilation of the circulatory system (afterload) MAP - CVP SVR = 80 x CO

Central Venous Pressure (CVP) mmHg – Measures blood volume returning to the heart (preload) – May be helpful in determining volume status – However, not an accurate predictor of volume responsiveness Pulmonary Capillary Wedge Pressure (PCWP) – Measures pressure in pulmonary artery – Indirect measure of left atrial pressure

Contractility Preload (CVP) Afterload Stroke Volume Heart Rate Cardiac Output Mean Arterial Pressure Systemic Vascular Resistance

Pulmonary Artery (PA) catheter – Advantage: Directly measures CO – Disadvantages: Difficult to place No superiority data May be arrhythmogenic

Central Venous Catheter (CVC) – Advantages: Easier and safer than PA catheter Can measure CVP Can measure ScvO 2 – Unless femoral CVC * * Chest 2010;138(1):76-83

Arterial pulse pressure waveform analysis – Many different brand names – Advantages: Continuous CO measurement Assessment of stroke volume and pulse pressure – As well as variation in these parameters – Disadvantages: Valve dysfunction and arrhythmias decrease accuracy SVV is only validated in intubated patients

Lactate – Product of anaerobic metabolism Elevation is a good marker of tissue hypoperfusion – Trending may be useful to grade, or possibly guide, resuscitation in septic shock – Can cause anion-gap metabolic acidosis

Central Venous Oxygen Saturation (ScvO 2 ) – Accurate measure of peripheral oxygen delivery Assuming patient is not profoundly anemic – When oxygen delivery is appropriate: SaO 2 – ScvO 2 = 25% (100% - 75% = 25%) 25% is the normal extraction ratio (ERO 2 ) – When oxygen delivery is inadequate: ERO 2 increases ScvO 2 decreases – Continuous monitoring is more appropriate than occasional

4 main types of shock: – Hypovolemic “Not enough blood” – Cardiogenic “Heart not working” – Obstructive “Something’s in the way” – Vasodilatory/Distributive “No pressure”

Shock State CVPPCWPCOSVR Hypovolemic Cardiogenic Obstructive Vasodilatory/Distributive

Hypovolemic shock – Characterized by inadequate blood volume – Causes: Hemorrhage (trauma, GI, post-partum, etc.) Burns Diarrhea/Vomiting Excessive perspiration – Treatment: Fix the underlying cause Replace volume lost Support BP if necessary

Cardiogenic shock – Inability of the heart muscle to adequately pump blood – Causes: Damage to the heart – Myocardial infarction, decompensated heart failure, mycordial/septal/valve rupture, arrhythmia (tachy or brady) – Treatment: Fix the underlying cause Stimulate the heart muscle Optimize fluid and BP

Obstructive shock – Interference with normal pumping by an outside force – Causes: Pulmonary embolism Cardiac tamponade Tension pneumothorax – Treatment: Fix the underlying cause Optimize fluid and BP

Vasodilatory/Distributive shock – Relative deficiency of volume due to loss of tone in vasculature – Causes: Sepsis Anaphylaxis Spinal cord injury Poisoning/Overdose – Treatment: Fix the underlying cause Increase blood volume Increase blood pressure

Definition: Drugs that cause either constriction or dilation of blood vessels – Inotropic drugs often lumped in as well Mostly analogues of naturally occurring chemicals within the body – Specifically chemicals that impact the adrenergic system – “Fight or Flight” response All should be run through a central line

BRAIN EXERTIONSTRESS HEART ADRENAL GLAND SPINALCORDSPINALCORD SPINALCORDSPINALCORD NOREPINEPHRINE BLOODSTREAM NOREPINEPHRINE EPINEPHRINE

Three primary receptor subtypes of concern – Alpha 1 Vasoconstriction – Beta 1 Increased heart rate and contractility – Beta 2 Bronchial and vascular dilation

DrugReceptors PhenylephrineAlpha 1 NorepinephrineAlpha 1 > Beta 1 EpinephrineAlpha 1 = Beta 1 DopamineBeta 1 > Alpha 1 DobutamineBeta 1 > Beta 2 VasopressinVasopressin receptors

Phenylephrine – Alpha 1 specific agent Increased SVR is primary action May decrease CO due to increased afterload – At normal doses may be less potent than other agents – Generally only recommended as salvage therapy

Norepinephrine – Primarily alpha 1 but some beta 1 activity Increased SVR May increase HR and contractility – Often not notable due to increased afterload – Preferred first line therapy in Septic Shock * – Less likely to cause tachycardia/arrhythmia than agents with more beta 1 activity – Effective in other vasodilatory shock states * Crit Care Med 2013;41(2):

Epinephrine – Equivocal alpha 1 and beta 1 activity Increased SVR Increased heart rate Increased contractility – May be considered as first or second line in septic shock * – Preferred therapy in anaphylactic shock * Crit Care Med 2013;41(2):

Dopamine – Receptor preference is dose dependent < 5 mcg/kg/min Primarily dopamine receptors Increased renal blood flow Small increase in contractility 5 – 10 mcg/kg/min Beta1 > Alpha1 Increased contractility Small increase in HR and SVR > 10 mcg/kg/min Alpha1 > Beta1 Increased SVR Increased HR and contractility

Dopamine (cont.) – Only recommended in septic shock when low risk of tachyarrhythmia or absolute or relative bradycardia * – Useful in certain cardiogenic shock populations Bradyarrhythmias – Not recommended for renal protection – Safer to administer peripherally than other agents * Crit Care Med 2013;41(2):

Dobutamine – Beta selective agent with mostly beta 1 activity Increased contractility Increased heart rate May decrease SVR, but usually not notable – First line agent for many cardiogenic shock patients Especially heart failure or bradyarrhythmia – May consider in septic shock if ScvO 2 persistently low after volume and MAP optimized * * Crit Care Med 2013;41(2):

Vasopressin – Most notable activities at V 1 a & V 2 receptors V 1 a receptor = direct vasoconstriction V 2 receptor = increased water resorption by kidneys – Usually second line agent (rarely used as monotherapy) – In septic shock low dose may decrease norepinephrine requirements – In hemorrhagic stroke (specifically variceal hemorrhage) high dose can be considered to decrease bleeding – Can be useful in difficult to wean patients

1.Identify the etiology of the shock 2.Treat the underlying cause 3.Target drugs to treat the dysfunctional circulation

83 y/o F found unresponsive at nursing home. Recent tx for UTI with levofloxacin Skin: Cold to the touch, poor turgor HR 122 BP 74/40 RR 25 Temp 102F WBC 15.6 Lactate 4.3 UA: + nitrites, gross pyuria Blood cults: 2/2 positive for GNR

What is the most likely etiology of shock? – Vasodilatory (septic) What is the optimal treatment? – Follow sepsis algorithm… – Early effective antibiotics (Fix underlying cause) – Fluids & vasopressors Norepinephrine preferred first line

77 y/o M with lightheadedness and fatigue 2 day history of increasing melena No history of liver disease HR 124 BP 88/54 RR 18 Temp 98.3 F Hgb 5.4 Hct 29% Stool guaiac positive

What is the most likely etiology of shock? – Hypovolemic (hemorrhagic) What is the optimal treatment? – Replace blood lost – Get him to the GI lab (Fix underlying cause) – May consider vasopressor if shock progressing despite blood/too unstable for GI lab

67 y/o F with shortness of breath and swelling Just returned from 7 day Mexican vacation History of AHA Stage C congestive heart failure Skin: Cool to touch, +3 pitting edema HR 72 BP 80/46 RR 24 Temp 99.0 F Chest Xray: Diffuse pulmonary edema

What is the most likely etiology of shock? – Cardiogenic (heart failure exacerbation) What is the optimal treatment? – Dobutamine to increase contractility and heart rate Attempt to mobilize fluid – Diuresis if blood pressure will tolerate – Fix underlying cause? LVAD or transplant

43 y/o M w/ chest pain and shortness of breath Acute onset today, returned from Dubai 3 days ago No past medical history HR 56 BP 70/53 RR 27 Temp F CT chest: large saddle pulmonary embolism TTE: severe RV dilation

What is the most likely etiology of shock? – Obstructive (pulmonary embolism) What is the optimal treatment? – Thrombectomy or thrombolysis (fix underlying cause) – Vasopressors unlikely to provide much benefit May increase stress on heart with marginal improvement in circulation

Early recognition and classification of shock syndrome can help to guide therapy Determining the underlying cause and rapidly fixing it (if possible) is the most effective therapy Commonly used vasopressors have different hemodynamic effects and should be selected based on goals of therapy

Michael D Schmidt, PharmD Critical Care Clinical Pharmacist Belleville Memorial Hospital Belleville, IL