VASOPRESSORS​ ​&​ ​INOTROPES

Mark​ ​Tuttle​ ​2017

DEFINITION​ ​OF​ ​SHOCK​:​ ​Inadequate​ ​tissue​ ​perfusion​ ​that​ ​results​ ​in​ ​end-organ​ ​dysfunction

MAP​ ​=​ ​CO​ ​x​ ​TPR    TYPES​ ​OF​ ​SHOCK Type​ ​of​ ​shock  Hypovolemic Cardiogenic Distributive  

PCWP  ↓ ↑ ↓

CO  ↓ ↓ ↑

SVR  ↑ ↑ ↓

SUBTYPES​ ​OF​ ​SHOCK ● Hypovolemic:​ ​Dehydration,​ ​blood​ ​loss ● Cardiogenic:​ ​Heart​ ​failure ○ Obstructive:​ ​Pulmonary​ ​embolism,​ ​cardiac​ ​tamponade, tension​ ​pneumothorax ● Distributive:​ ​Sepsis,​ ​anaphylaxis,​ ​neurogenic,​ ​adrenal

Agent  α​1  β​1  β​2  D  V  CO  Norepinephrine​ ​(​Levophed​) ++ ++ 0 0 0 -/↑ Dobutamine 0 +++ ++ 0 0 ↑ Isoproterenol 0 +++ +++ 0 0 ↑ Milrinone* 0 ++* ++* 0 0 ↑ Epinephrine +++ +++ ++ 0 0 ↑↑ Dopamine​ ​(0.5-2) 0 0 0 + 0 ↑ Dopamine​ ​(5-10) 0 ++ 0 + 0 ↑↑ Dopamine​ ​(>10) ++ 0 0 + 0 ↑ Vasopressin 0 0 0 0 + 0 Phenylephrine​ ​(​Neosynephrine​) +++ 0 0 0 0 0 *Phosphodiesterase​ ​III​ ​inhibitor​ ​works​ ​downstream​ ​of​ ​beta​ ​receptors

SVR  ↑↑ ↓ ↓ ↓ ↑ ↓ ↑ ↑ ↑↑

Receptor  Action  α​1 Vasoconstriction β​1  Inotropy,​ ​chronotropy,​ ​dromotropy β​2  Inotropy,​ ​vasodilation D  Vasoconstriction,​ ​vasodilation​ ​of splanchinc,​ ​chronotropy V  Vasoconstriction  

VASOPRESSORS​:​ ​Indicated​ ​if​ ​fluids​ ​fail​ ​to​ ​restore​ ​MAP​ ​>​ ​60-65.​ ​ ​Distinct​ ​(mostly)​ ​from​ ​inotropes. ● Norepinephrine​ ​(​Levophed​)​:​ ​First​ ​line​ ​in​ ​cardiogenic​ ​and​ ​septic​ ​shock ○ α-agonist​ ​with​ ​less​ ​β​ ​stimulation,​ ​so​ ​predominantly​ ​increases​ ​vascular​ ​resistance ○ Better​ ​head​ ​to​ ​head​ ​versus​ ​dopamine​2 ● Dopamine​:​ ​Endogenous​ ​vasopressor​ ​and​ ​is​ ​a​ ​precursor​ ​of​ ​epinephrine​ ​and​ ​norepinephrine ○ Low​ ​doses:​ ​Acts​ ​on​ ​D​ ​receptors,​ ​selective​ ​vasodilation​ ​of​ ​coronary,​ ​renal,​ ​mesenteric​ ​beds ■ No​ ​difference​ ​in​ ​urine​ ​output,​ ​need​ ​for​ ​RRT,​ ​or​ ​survival​ ​compared​ ​with​ ​placebo​1 ○ Medium​ ​doses:​ ​β​1​​ ​stimulation​ ​increase​ ​heart​ ​rate​ ​and​ ​contractility ○ High​ ​doses:​ ​α1​​ ​ ​effects​ ​predominate,​ ​increasing​ ​vascular​ ​resistance ○ May​ ​have​ ​more​ ​chronotropic​ ​effect​ ​than​ ​others ● Epinephrine​:​ ​Potent​ ​β​1​​ ​and​ ​moderate​ ​β​2​​ ​and​ ​α​1​​ ​effects.​ ​ ​First-line​ ​in​ ​anaphylactic​ ​shock. ○ Low​ ​doses:​ ​β1​​ ​ ​effects​ ​predominate,​ ​increasing​ ​cardiac​ ​output ○ High​ ​doses:​ ​α​1​​ ​effects​ ​predominate,​ ​increasing​ ​vascular​ ​resistance. ● Phenylephrine​ ​(​NeoSynephrine​):​​ ​Pure​ ​α1​​ ​ ​effects,​ ​↑​ ​SVR​ ​without​ ​affecting​ ​inotropy​ ​or​ ​chronotropy. ○ Good​ ​choice​ ​in​ ​patients​ ​with​ ​tachyarrhythmias. ○ Less​ ​useful​ ​in​ ​cardiogenic​ ​shock​ ​since​ ​already​ ​↑​ ​SVR. ○ At​ ​increasing​ ​doses​ ​can​ ​suppress​ ​atrial​ ​arrhythmias​ ​due​ ​to​ ​increased​ ​vagal​ ​tone ● Vasopressin​:​ ​can​ ​be​ ​effective​ ​in​ ​severe​ ​sepsis​ ​and​ ​septic​ ​shock​ ​refractory​ ​to​ ​other​ ​vasopresors ○ Study​ ​showed​ ​no​ ​mortality​ ​benefit​ ​when​ ​combined​ ​with​ ​norepinephrine​1​. ● Dobutamine​:​ ​Selective​ ​β​ ​inotrope. ○ Reserve​ ​for​ ​patients​ ​with​ ​low​ ​cardiac​ ​output​ ​with​ ​adequate​ ​LV​ ​filling​ ​pressure​ ​and​ ​MAP ● Milrinone​:​ ​Phosphodiesterase​ ​III​ ​inhibitor​ ​increases​ ​cAMP​ ​levels​ ​downstream​ ​of​ ​beta​ ​receptors ○ Inodilator ○ Can​ ​treat​ ​beta​ ​blocker​ ​overdose​ ​since​ ​works​ ​downstream​ ​of​ ​beta​ ​receptor  MarkTuttleMD.com

VASOPRESSORS​ ​&​ ​INOTROPES

Mark​ ​Tuttle​ ​2017

THE​ ​EVIDENCE ● Cochrane​ ​review​3​:​ ​Insufficient​ ​data​ ​to​ ​make​ ​a​ ​recommendation ● SOAP​ ​II​ ​Trial​2​:​​ ​Dopamine​ ​versus​ ​norepinephrine​ ​in​ ​shock​ ​(cardiogenic​ ​and​ ​septic) a. ​ ​At​ ​28​ ​days,​ ​there​ ​was​ ​no​ ​difference​ ​in​ ​all-cause​ ​mortality​ ​though​ ​there​ ​was​ ​a​ ​significantly​ ​higher​ ​rate​ ​of​ ​arrhythmias in​ ​the​ ​dopamine​ ​group​ ​(24.1%​ ​vs.​ ​12.4%;​ ​P<0.001) ● Phenylephrine​ ​versus​ ​norepinephrine​ ​in​ ​sepsis​ ​RCT​:​ ​No​ ​difference​4 ● Surviving​ ​sepsis​ ​campaign​ ​guidelines​5  1. Norepinephrine 2. Epinephrine 3. Vasopressin ● Milrinone​ ​vs.​ ​placebo​ ​in​ ​acute​ ​heart​ ​failure​6​:​ ​No​ ​difference​ ​in​ ​mortality ○ Increased​ ​risk​ ​of​ ​hypotension​ ​and​ ​atrial​ ​arrhythmias​ ​with​ ​milrinone SOURCES  1. Overgaard​ ​CB,​ ​Dzavík​ ​V.​ ​Inotropes​ ​and​ ​vasopressors:​ ​review​ ​of​ ​physiology​ ​and​ ​clinical​ ​use​ ​in​ ​cardiovascular​ ​disease. Circulation.​ ​2008;118(10):1047-56. 2. De​ ​backer​ ​D,​ ​Biston​ ​P,​ ​Devriendt​ ​J,​ ​et​ ​al.​ ​Comparison​ ​of​ ​dopamine​ ​and​ ​norepinephrine​ ​in​ ​the​ ​treatment​ ​of​ ​shock.​ ​N​ ​Engl​ ​J Med.​ ​2010;362(9):779-89. 3. Müllner​ ​M,​ ​Urbanek​ ​B,​ ​Havel​ ​C,​ ​Losert​ ​H,​ ​Waechter​ ​F,​ ​Gamper​ ​G.​ ​Vasopressors​ ​for​ ​shock.​ ​Cochrane​ ​Database​ ​Syst​ ​Rev. 2004;(3):CD003709. 4. Morelli​ ​A,​ ​Ertmer​ ​C,​ ​Rehberg​ ​S,​ ​et​ ​al.​ ​Phenylephrine​ ​versus​ ​norepinephrine​ ​for​ ​initial​ ​hemodynamic​ ​support​ ​of​ ​patients​ ​with septic​ ​shock:​ ​a​ ​randomized,​ ​controlled​ ​trial.​ ​Crit​ ​Care.​ ​2008;12(6):R143. 5. Dellinger​ ​RP,​ ​Levy​ ​MM,​ ​Rhodes​ ​A,​ ​et​ ​al.​ ​Surviving​ ​sepsis​ ​campaign:​ ​international​ ​guidelines​ ​for​ ​management​ ​of​ ​severe​ ​sepsis and​ ​septic​ ​shock:​ ​2012.​ ​Crit​ ​Care​ ​Med.​ ​2013;41(2):580-637. 6. Cuffe​ ​MS,​ ​Califf​ ​RM,​ ​Adams​ ​KF,​ ​et​ ​al.​ ​Short-term​ ​intravenous​ ​milrinone​ ​for​ ​acute​ ​exacerbation​ ​of​ ​chronic​ ​heart​ ​failure:​ ​a randomized​ ​controlled​ ​trial.​ ​JAMA.​ ​2002;287(12):1541-7.

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