1. Vasopressors and Inotropes Critical Care Lecture Series

2. ICU Objectives What are the different classes of shock and give examples of each. What are the different classes of shock and give examples of each. Discuss how to investigate and the management principles behind each of the causes of shock. Discuss how to investigate and the management principles behind each of the causes of shock. What are the different crystalloids and colloids available for resuscitation? What are the different crystalloids and colloids available for resuscitation? Have knowledge of the mechanism of action of commonly used vasopressors and inotropes, including dopamine, dobutamine, milnerone, levophed, phenylephrine, epinephrine, vasopressin Have knowledge of the mechanism of action of commonly used vasopressors and inotropes, including dopamine, dobutamine, milnerone, levophed, phenylephrine, epinephrine, vasopressin Discuss adverse events associated with the above agents. Discuss adverse events associated with the above agents.

3. ICU Is My Patient in Shock? Definition of shock Definition of shock Inadequate end organ perfusion leading to inadequate oxygen delivery Inadequate end organ perfusion leading to inadequate oxygen delivery N.B. a patient in shock does not have to be hypotensive N.B. a patient in shock does not have to be hypotensive

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5. Treatment of Shock Basic Resuscitation: ABCDE’s Basic Resuscitation: ABCDE’s A: Airway establishment A: Airway establishment B: Breathing: control WOB B: Breathing: control WOB C(a): Circulation Optimization C(a): Circulation Optimization C(b): Control O2 consumption C(b): Control O2 consumption D: Delivery of O2 adequately D: Delivery of O2 adequately E Extraction of O2 E Extraction of O2

6. ICU Fluid resuscitation Very important…. Very important…. Therapy with least detrimental effects Therapy with least detrimental effects Fluid therapy may be beneficial in any type of shock Fluid therapy may be beneficial in any type of shock Even cardiogenic shock/pulmonary edema Even cardiogenic shock/pulmonary edema

7. ICU Fluid Resusitation Must “test the patient” Must “test the patient” Give volume and look for response/improvement Give volume and look for response/improvement Always start with NS of RL Always start with NS of RL ? Need blood ? Need blood Must always look for the effect of treatment Must always look for the effect of treatment Re-evaluate patient after fluid Re-evaluate patient after fluid If no improvement, and no adverse effects, repeat If no improvement, and no adverse effects, repeat If adverse effect, needs inotropes/vasopressor if still in shock If adverse effect, needs inotropes/vasopressor if still in shock Too much: pulmonary edema (O 2 sats) Too much: pulmonary edema (O 2 sats)

8. ICU A: Airway establishment Indications for intubation: 1. Failure of oxygenation or ventilation 2. Failure to protect airway 3. Condition present or procedure needed that will require intubation “shock” is an indication for intubation Hypotension common after intubation

9. ICU B: Breathing: control WOB Respiratory muscles are significant consumers of oxygen Respiratory muscles are significant consumers of oxygen Control will allow better O2 delivery to other tissues Control will allow better O2 delivery to other tissues Sedation after intubation Sedation after intubation

10. ICU C(a): Circulation Optimization Most causes of shock require some volume re-expansion – even cardiogenic shock Most causes of shock require some volume re-expansion – even cardiogenic shock - Starling curve Crystalloid as good as colloid Crystalloid as good as colloid Vasopressors ineffective if hypovolemic Vasopressors ineffective if hypovolemic “double edged sword” “double edged sword”

11. ICU C(b): Control O2 consumption Reduce hyper-adrenergic state Reduce hyper-adrenergic state Analgesia/sedation/muscle relaxation Analgesia/sedation/muscle relaxation temperature temperature

12. ICU D: Delivery of O2 adequately Follow sats (keep > 92%) Follow sats (keep > 92%) ? Transfusion (Hbg >80-100) ? Transfusion (Hbg >80-100) Lactate Lactate SmvO2 SmvO2

13. ICU E: Extraction of O2 O2 must get from lungs to Hbg to tissues O2 must get from lungs to Hbg to tissues O2 extraction important in some types of shock O2 extraction important in some types of shock Cyanide, MetHbg, SEPSIS Cyanide, MetHbg, SEPSIS

14. ICU ABCDE’s: Summary A: Airway establishment: 02,biPap, ETT A: Airway establishment: 02,biPap, ETT B: Breathing: control WOB: Sedation, analgesia B: Breathing: control WOB: Sedation, analgesia C(a): Circulation Optimization: fluids, inotropes, pressors C(a): Circulation Optimization: fluids, inotropes, pressors C(b): Control O2 consumption: sedation, temp control, seizure control C(b): Control O2 consumption: sedation, temp control, seizure control D: Delivery of O2 adequately: Hbg, fluid, pressor, inotropes D: Delivery of O2 adequately: Hbg, fluid, pressor, inotropes E: Extraction of O2: R/O cyanide, metHbg, sepsis E: Extraction of O2: R/O cyanide, metHbg, sepsis

15. ICU Vasopressors Many different pressors/inotropes Many different pressors/inotropes Need to understand how they work to use effectively Need to understand how they work to use effectively If choose wrong one, or use inappropriately, can harm the patient If choose wrong one, or use inappropriately, can harm the patient Adrenergic precipitation of arrhythmias Adrenergic precipitation of arrhythmias Drive the heart too fast resulting in decreased filling time and decreased stroke volume Drive the heart too fast resulting in decreased filling time and decreased stroke volume Vasoconstriction of splachnic circulation and coronary arteries Vasoconstriction of splachnic circulation and coronary arteries Inotropes may make certain patients hypotensive Inotropes may make certain patients hypotensive

16. ICU Vasopressors β1 agonist/stimulation: chronitropic, inotropic β1 agonist/stimulation: chronitropic, inotropic β2 agonist/stimulation: vasodilation, bronchodilation β2 agonist/stimulation: vasodilation, bronchodilation α: vasoconstriction α: vasoconstriction D: increases renal blood flow D: increases renal blood flow

17. ICU Vasopressors and inotropes: the chart (everything you need to know) Need CO Need nothing Need BP and CO Need BP Blood pressure Cardiac Output LowNormal Low Normal

18. ICU Dopamine Dopaminergic, Beta, Alpha: ranges ? Dopaminergic, Beta, Alpha: ranges ? Dopa: 1-5 ug/kg/min Dopa: 1-5 ug/kg/min ? Renal flow ? Renal flow Beta: 5-10 ug/kg/min Beta: 5-10 ug/kg/min Inoptropy/chronotropy Inoptropy/chronotropy Alpha: >10 ug/kg/min Alpha: >10 ug/kg/min Vasoconstriction Vasoconstriction Major use: increasing HR, ? bp Major use: increasing HR, ? bp

19. ICU Dobutamine Beta (little alpha) Beta (little alpha) Inotropic/chronotropic Inotropic/chronotropic 2-20 ug/kg/min 2-20 ug/kg/min Major use: Systolic dysfunction Major use: Systolic dysfunction Caveat: can/will decrease MAP Caveat: can/will decrease MAP

20. ICU Milrinone Used as an inotrope Used as an inotrope Mechanism of Action Mechanism of Action Phosphodiesterase inhibitor Phosphodiesterase inhibitor decrease the rate of cyclic AMP degradation decrease the rate of cyclic AMP degradation increase in cyclic AMP concentration leads to enhanced calcium influx into the cell, a rise in cell calcium concentration, and increased contractility increase in cyclic AMP concentration leads to enhanced calcium influx into the cell, a rise in cell calcium concentration, and increased contractility Side Effects Side Effects can also cause vasodilatation but tends to have less chronotropy than dobutamine can also cause vasodilatation but tends to have less chronotropy than dobutamine Onset of action Onset of action 5-15 minutes 5-15 minutes Duration Duration Half life of approximately 2 hours (so its gonna last a while Half life of approximately 2 hours (so its gonna last a while Dose Dose Loading dose: 50 mcg/kg administered over 10 minutes followed by 0.375 mcg/kg/minute Loading dose: 50 mcg/kg administered over 10 minutes followed by 0.375 mcg/kg/minute

21. ICU Phenylepherine Pure alpha agonist Pure alpha agonist Vasoconstrictor with no effect on inotropy/chronotropy Vasoconstrictor with no effect on inotropy/chronotropy 0.2-3.0 ug/kg/min 0.2-3.0 ug/kg/min Major use: non-cardiogenic hypotension Major use: non-cardiogenic hypotension

22. ICU Norepinepherine Alpha and Beta Alpha and Beta 0.02-3.0 ug/kg/min 0.02-3.0 ug/kg/min Major Use: when you need A&B Major Use: when you need A&B ? Drug of choice for septic shock ? Drug of choice for septic shock

23. ICU Epinepherine Alpha and Beta Alpha and Beta 0.01 – 1.0 ug/kg/min 0.01 – 1.0 ug/kg/min Major Use: when you need A&B Major Use: when you need A&B resuscitation resuscitation

24. ICU Vasopressors and inotropes DobutamineMilrinonenothing DopamineLevophedEpinepherineOrDobutamine/phenylPhenylepherineLevophed(dopamine) Blood pressure Cardiac Output LowNormal Low Normal

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26. Overview of the Management of Shock

27. ICU Case Study 65 yo male presents to ED 65 yo male presents to ED Complaining of cough and feeling very unwell Complaining of cough and feeling very unwell HR 120, BP 100/60, RR 30, temp 39 HR 120, BP 100/60, RR 30, temp 39 Is this patient in shock? Is this patient in shock? What investigations What investigations What treatment would you start? What treatment would you start?

28. ICU The patient’s BP drops to 90/50, what would you do now? The patient’s BP drops to 90/50, what would you do now? Would you start pressors? Which one? Would you start pressors? Which one? Case Study

29. ICU Case Study The patient is on 0.8ug/kg/min of levophed through a femoral line. Why might the patient not be responding to the vasopressors? What measurement would be helpful in improving this man’s MAP? The patient is on 0.8ug/kg/min of levophed through a femoral line. Why might the patient not be responding to the vasopressors? What measurement would be helpful in improving this man’s MAP?

30. ICU Case Study The patient has been resuscitated, now has a BP of 110/90. HR 65. His JVP is 12. His lactate continues to rise however. He is also anuric. Is this patient in shock? What is your management now? The patient has been resuscitated, now has a BP of 110/90. HR 65. His JVP is 12. His lactate continues to rise however. He is also anuric. Is this patient in shock? What is your management now?

31. ICU Summary Shock can be the consequence of decreased SVR, decreased CO or both. Shock can be the consequence of decreased SVR, decreased CO or both. Management of shock should be tailored to the physiologic state of the patient of the patient. Management of shock should be tailored to the physiologic state of the patient of the patient. Drugs are available to augment SVR, HR, afterload and contractility. Drugs are available to augment SVR, HR, afterload and contractility. Remember to optimize preload and consider the oxygen carrying capacity of the blood. Remember to optimize preload and consider the oxygen carrying capacity of the blood.