Rational choice of inotropes and vasopressors in intensive care unit
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The presentation introduces commonly used interpose and vasopressors; their classification; and how to choose the drug in ICU. Clinical scenarios - cariogenic shock; neurocritical care; septic shock and anaphylactic shock are elaborated.
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Rational choice of inotropes and vasopressors in intensive care unit
- 1. inotropes vasopressors INOTROPES VASOPRESSORS R A T I O N A L E O F C H O I C E Sultan Qaboos University Hospital, Muscat
- 2. inotropes vasopressors INOTROPES VASOPRESSORS SHOCK SEPSIS CARDIAC FAILURE VASST NOREPINEPHRINE DOBUTAMINE DOPAMINE RENAL DOSE HYPOVOLEMIA RECEPTORS LEVOSIMENDAN CATECHOLAMINES PHENYLEPHRINE VASOPRESSIN
- 3. inotropes vasopressors INOTROPES & VASOPRESSORS Basics Patient – clinical features Pathophysiology Monitoring Equipments Drugs Shock CO, SV SVR Preload Afterload
- 5. inotropes vasopressors Hemodynamics in Shock Low SVR (arteriolar tone) Low CO
- 6. inotropes vasopressors Hemodynamics in Shock • Inadequate CO • Comp. vasoconstriction • Elevated SVR COLD SHOCK • Inadequate SVR • Pathologic vasodilatation • Comp. elevated CO WARM SHOCK Fluid resuscitation Myocardial dysfunction
- 7. inotropes vasopressors Planning your strategy
- 8. inotropes vasopressors Adrenergic receptors and vasoactive agents α βα =β EpinephrinePhenylephrine Norepinephrine Dopamine IsoproterenolDobutamine Epinephrine Phenylephrine Norepinephrine Dopamine Isoproterenol Dobutamine High dose Low dose
- 9. inotropes vasopressors Direct inotropic effectsPeripheralvasculareffects YESNOVasodilatationVasoconstriction INOTROPES VASOPRESSORS
- 10. inotropes vasopressors Direct inotropic effectsPeripheralvasculareffects YESNOVasodilatationVasoconstriction INOTROPES VASOPRESSORS Inoconstrictors Norepinephrine Epinephrine Dopamine Inodilators Dobutamine Milrinone Vasoconstrictors Phenylephrine Vasopressin Vasodilators Nitroglycerine Nitroprusside Nesiritide
- 11. inotropes vasopressors Vasoconstriction Vasodilation Positive Inotropy Vasopressin Phenylephrine Norepinephrine LD Epinephrine/Dopamine Dobutamine HD Dopamine HD Epinephrine Nitroprusside
- 13. inotropes vasopressors HOW DO I MAKE MY CHOICE?
- 14. inotropes vasopressors Rationale of choice
- 15. inotropes vasopressors Rationale of choice Vasopressor Rx Restoration of adequate BP BP does NOT always equate to blood flow
- 16. inotropes vasopressors Rationale of choice Inotrope Rx Increase Cardiac Output To determine whether CO is adequate in patients with shock is a thorny problem.
- 17. inotropes vasopressors Hypotension – reduced perfusion pressure Abnormal shunting of blood flow within organs Cellular alterations – inability to use delivered substrates Down-regulation of adrenergic receptors
- 18. inotropes vasopressors Volume status Vasopressors Inotropes Monitors • Restore effective tissue perfusion • Normalise cellular metabolism
- 21. inotropes vasopressors INOTROPES VASOPRESSORS Ventricular arrhythmias Contraction- band necrosis Infarct expansion Compromised myocardial perfusion Elevated LV filling pressures Increased myocardial O2 reqrmt Further reduction in CPP Critical hypotension
- 23. inotropes vasopressors SBP 70-100mmHgNo S/S of Shock S/S of Shock + Moderate doses of these agents maximize inotropy and avoid excessive α1-adrenergic stimulation that can result in end-organ ischemia.
- 24. inotropes vasopressors SBP <70 mmHg; Inadequate response to medium dose DOPAMINE or DOPAMINE/DOBUT + antithrombotic effects
- 25. inotropes vasopressors SBP <70 mmHg; Inadequate response to medium dose DOPAMINE or DOPAMINE/DOBUT Promote thrombosis in coronary vasculature Exacerbate lactic acidosis
- 26. inotropes vasopressors NOREPINEPHRINE-resistant vasodilatory shock Improve MAP, Cardiac index LV stroke work Reduce NorEpi dose Improve Coronary blood flow (catecholamine sparing)
- 27. inotropes vasopressors TRAUMATIC BRAIN INJURY ACUTE NEUROLOGIC INJURY
- 29. inotropes vasopressors September 2008 - Volume 36 - Issue 9 - pp 2641-2650 doi: 10.1097/CCM.0b013e3181847af3 After 2hrs of resuscitation of TBI, phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure >70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure >12 mm Hg plus glucose to maintain normoglycemia. Vasopressin Phenylephrine ICP Brain tissue PO2 Peripheral tissue PO2 +10mmHg +6mmHg +10%
- 30. inotropes vasopressors Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock. Intensive Care Med 2013; 39(2): 165-228 and Crit Care Med 2013; 41(2): 580- 637
- 31. inotropes vasopressors Vasopressor therapy initially to target MAP 65mmHg
- 32. inotropes vasopressors • Improves systemic blood pressure • Does not substantially worsen end-organ ischemia in most studies of crystalloid-resuscitated septic shock patients • Equivalent efficacy in increasing mean arterial pressure, oxygen consumption, and oxygen delivery compared with other catecholamine pressors • Gastric pH has been observed to increase (not decrease)
- 33. inotropes vasopressors • Epinephrine is added to and potentially substituted for NE when an additional agent is needed to maintain adequate MAP • DOPAMINE is an alternative agent to NE only in highly selected patients (eg, patients with low risk of tachyarrhythmias and absolute or relative bradycardia)
- 34. inotropes vasopressors • NOT recommended in the Rx of shock except: a) NE associated with serious arrhythmias b) CO is known to be high and BP persistently low c) As salvage Rx when combined inotrope/vasopressor drugs and low dose vasopressin have failed to achieve MAP target
- 35. inotropes vasopressors • VP 0.03U/min can be added to NE with intent of either raising MAP or decreasing NE dosage • Low dose VP is NOT recommended as the single initial vasopressor • VP doses higher than 0.03-0.04U/min should be reserved for salvage Rx
- 36. inotropes vasopressors • 778 patients with septic shock randomly assigned to either low dose vasopressin (0.01 to 0.03 units per minute) norepinephrine (5 to 15 mcg per minute) • similar 28-day and 90-day mortality rates, similar incidence of serious adverse events VasopressinandSepticShockTrial(VASST) Russell JA, Walley KR, Singer J, Gordon AC, Hébert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D, VASST Investigators. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358(9):877
- 37. inotropes vasopressors • Annane et al, Lancet 2007; 370: 676–84, 330 patients with septic shock in French ICU’s • Titrated to maintain MAP at 70mmHg, Primary outcome 28 day mortality
- 39. inotropes vasopressors Potentially lifesaving Antagonizes the effects of the released mediators Maintains blood pressure
- 42. inotropes vasopressors Drug Mechanism Action Enoximone, milrinone Phosphodiesterase III (PDE III) inhibitor, prevent hydrolysis of intracellular cyclic AMP, augmenting its effects. Many isoenzymes of phosphodiesterase – PDE III is the target for inotropic actions Increased cardiac contractility and stroke volume, vasodilatation Levosimendan Calcium sensitizer. Increases the sensitivity of myocardial troponin to intracellular calcium, possible inhibition of PDE III Increased cardiac contractility without increasing myocardial oxygen demand, effect on mortality unclear Vasopressin Endogenous hormone, also called antidiuretic hormone, V1 receptor activity in vascular smooth muscle increasing intracellular calcium Vasoconstriction increasing systemic vascular resistance and blood pressure
Editor's Notes
- Trend towards increased survival however not significant
- At day 28, there were 64 (40%) deaths in the epinephrine group and 58 (34%) deaths in the norepinephrine plus dobutamine group (p=0·31; relative risk 0·86, 95% CI 0·65–1·14). There was no significant difference between the two groups in mortality rates at discharge from intensive care (75 [47%] deaths vs 75 [44%] deaths, p=0·69), at hospital discharge (84 [52%] vs 82 [49%], p=0·51), and by day 90 (84 [52%] vs 85 [50%], p=0·73), time to haemodynamic success (log-rank p=0·67), time to vasopressor withdrawal (log-rank p=0·09), and time course of SOFA score. Rates of serious adverse events were also similar. Interpretation There is no evidence for a difference in efficacy and safety between epinephrine alone and norepinephrine plus dobutamine for the management of septic shock.