Uploaded on

 

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
No Downloads

Views

Total Views
2,963
On Slideshare
0
From Embeds
0
Number of Embeds
0

Actions

Shares
Downloads
200
Comments
0
Likes
6

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide

Transcript

  • 1. Vasoactive Agentsin Emergency CareSusan P. Torrey, M.D., FACEPBaystate Medical CenterTufts University School of Medicine
  • 2. Vasopressors for shockCochrane Database of Systematic Reviews • “The current available evidence is not suited to inform clinical practice.” • Mullner, et al. 2005
  • 3. Vasopressors for shockCochrane Database of Systematic Reviews • “there is not sufficient evidence to prove that any of the vasopressors…were superior to others” • Havel, et al. 2011
  • 4. Adrenergic receptorphysiology• α1 adrenergic receptors• β1 adrenergic receptors• β2 adrenergic receptors
  • 5. Adrenergic receptorphysiology• α1 adrenergic receptors – vasoconstriction of many vascular beds – smooth muscle in arterioles • skin, mucosa, skeletal muscle, kidneys • not cerebral and cardiac – positive inotropic response in myocardium • with little effect on heart rate  norepinephrine, epinephrine, +/- dopamine
  • 6. Pressure-dependent vascular beds• Heart and brain (without α-receptors) – ↑blood flow as MAP increases• Gut and kidney (with α-receptors) – ↑blood flow as MAP ↑ to some minimal level – then vasoconstriction  gut and renal ischemia• Two primary principles of vasopressor use – a minimal MAP is imperative (MAP 65) – excessive vasopressors  vital organ compromise
  • 7. Adrenergic receptorphysiology• β1 adrenergic receptors – predominant adrenergic receptor in myocardium – positive inotropic and chronotropic response  dobutamine, isoproterenol, epinephrine
  • 8. Adrenergic receptorphysiology• β2 adrenergic receptors – vasodilation in muscles (bronchial, uterine)  terbutaline (bronchodilator, tocolytic)
  • 9. Effects of adrenergic agents vasopressor β1 β2 α1 expected effectsDopamine ++ + ++ ↑CI,↑MAP,↑SVRDobutamine +++ + + ↑↑CI, -/↑ MAPIsoproterenol +++ +++ 0 ↑↑HRNorepinephrine ++ 0 +++ ↑↑MAP, ↑↑SVREpinephrine +++ ++ +++ ↑↑CI, ↑MAPPhenylephrine 0 0 +++ ↑↑MAP, ↑↑SVR
  • 10. Dopamine• Dose-dependent stimulation – Low-dose (< 5 μg/kg/min) • dopaminergic receptors – Moderate dose (5-10 μg/kg/min) • β1 stimulation  ↑cardiac output – High dose (> 10 μg/kg/min) • α1 stimulation  ↑ SVR
  • 11. Dopamine• Expect ↑ MAP of ~ 25%• Adverse effects – tachycardia, tachyarrhythmias – vasoconstriction-induced myocardial ischemia – ↓ splanchnic perfusion  multiple organ failure
  • 12. Dobutamine• Potent nonselctive β- and mild α-stimulation – ↑ cardiac contractile force – +/- ↑ heart rate – ↓ cardiac-filling pressure• Indications – decompensated CHF – with norepinephrine if CI ≤ 3 L/min/m2• Dosage: 2 – 20 μg/kg/min
  • 13. Epinephrine• Potent α- and β-agonist – vasoconstriction  ↑ MAP – ↑contractility and heart rate  ↑cardiac output• Indications  for low cardiac output states – cardiovascular resuscitation – anaphylaxis
  • 14. Norepinephrine• Potent α1 and β1 agonist with little β2 activity – α stimulation  vasoconstriction – β1 effects balanced by reflex activity  little effect on heart rate and cardiac output• Indications – an excellent vasopressor• Dosage: 0.5 – 30 μg/min
  • 15. Phenylephrine• Selectively stimulates α1 receptors – vasoconstriction  ↑SVR – as BP increases, vagal reflexes  ↓heart rate• Pure α-adrenergic agent – no ↑inotropy – distributive shock often  cardiac depression – restoring MAP without ↑inotropy  ↓C.O.
  • 16. Phenylephrine • Indications – anesthesia-induced hypotension – spinal shock – useful with tachycardia • arrhythmias with other vasopressors
  • 17. Isoproterenol• Potent nonselective β activity – inotropic and chronotropic effects  ↑CO• Indications – temporary treatment of bradycardia – overdrive “pacing” for torsade de pointes
  • 18. Vasopressin• Antidiuretic hormone – V2 receptors on renal tubules  water resorption• An important stress hormone – V1 receptors on vessels  vasoconstriction – V3 receptors in pituitary  ACTH production – ↑ BP only with relative hypovolemia • SIADH does not cause hypertension
  • 19. Vasopressin• Indications – catecholamine resistance in sepsis – cardiac arrest unresponsive to epinephrine – may be useful for “irreversible” shock• Dosage – Shock – 0.01 to 0.05 U/min by infusion – ACLS – 40 U as IV bolus
  • 20. Push-dose Pressors• Phenylephrine – In 3ml syringe, draw up 1ml from vial 10mg/ml – Inject this into 100ml bag normal saline – Thus 100ml phenylephrine of 100μg/ml – Draw solution into syringe; each ml = 100μg – Dose: 0.5 – 2 ml every 2-5 min (50 – 200 μg)• Epinephrine – Draw 9ml of NS into 10ml syringe – Add 1 ml of 1:10,000 epinephrine (100μg/ml) – Thus 10 ml of epi at 10 μg/ml – Dose: 0.5 – 2 ml every 2-5 min (5 – 20 μg)
  • 21. Case #150-year-old man with urticaria after bee-sting.VS: 78/40, 130, 26, 90% O2Rx: epinephrine 0.3 mg SQ anddiphenhydramine 50 mg IM continued hypotension with confusion
  • 22. Anaphylaxis• Epinephrine 0.3 – 0.5 mg (0.3 –0.5 ml of 1:000) – SQ absorption slow – give IM – marked vasoconstriction – urticaria – β-blocker controversy • epi less effective  give more • unopposed α-effect  give less
  • 23. Unresponsiveto IM epinephrine• More epinephrine – Push-dose epinephrine (100μg over 5-10 min) – IV infusion – 0.5 to 1.0 µg/min up to 10 µg/min• Glucagon – 1 – 5 mg IV over 5 min – then 5 – 15 μg/min infusion• Vasopressin ?
  • 24. Vasopressin ?• Schummer Anesth Analg 2008 – Six cases of anesthesia-induced anaphylaxis, unresponsive to epinephrine and fluids, had prompt hemodynamic stabilization after vasopressin (2 – 8 U). – Helpful even in patients on β-blockers.
  • 25. Case #270-year-old woman with altered mental status.PMH: CAD with CHF, HTN, dementiaVS: 80/48, 110, 22, 100.8°, 88% O2Labs:  WBC,  BUN/Cr,  CO2, pyuria remains hypotensive despite 2 liters NS IV
  • 26. Current Rx of septic shock • Aggressive fluid resuscitation – 4 - 6 liters of crystalloid (or colloid) – Vasopressors to support BP (MAP ≥ 65 mmHg) • Dopamine or norepinephrine initially – Adjuncts to therapy • early antibiotics • Corticosteroid ? • Activated protein C ?? Dellinger Surviving Sepsis Campaign Crit Care Med 2008
  • 27. The Evidence• Annane Lancet 2007 – prospective, randomized, double-bind study – 330 patients with septic shock from France – epinephrine or norepinephrine plus dobutamine – titrated to MAP ≥ 70mmHg – no difference in 28-day mortality or safety
  • 28. The Evidence• Morelli Crit Care 2008 – prospective, randomized, controlled study – 32 patients with septic shock from Rome – MAP < 65mmHg despite adequate fluid – norepinephrine or phenylephrine for MAP 65-75 – over initial 12 hours, no differences in: • cardiopulmonary performance • global oxygen transport • regional hemodynamics
  • 29. The Evidence• Myburgh Intensive Care Med 2008 – Prospective, double-blind, randomized – 280 patients from Australia – norepinehrine or epinephrine for MAP ≥ 70mmHg – no difference to achieve MAP goal or mortality – Epinephrine had significant but transient metabolic effects  withdrawal of 13% epinephrine group
  • 30. The Evidence• DeBacker Lancet 2010 – Randomized trial of 1679 patients with shock – either dopamine (to 20μg/kg/min) or norepinephrine (up to 0.19μg/kg/min) – no difference in rate of death at 28 days – more arrhythmias in dopamine group (24% vs 12%)
  • 31. Initial choice of vasopressor • With cardiac index ≥ 3.0 L/min/m2 – Norepinephrine is first choice – Phenylephrine, if brief and no cardiac dysfunction • With cardiac index < 3.0 L/min/m2 – need more inotropic support… – Dopamine – Norepinephrine plus dobutamine • Another possibility – Epinephrinemm Kellum Curr Opin Crit Care 2002
  • 32. If high-dose vasopressors aren’t enough? • Addition of vasopressin may augment vasopressor treatment in septic shock • Patel Anesth 2002 – 24 patients with severe septic shock on high- dose norepinephrine – randomized and blinded to either more norepi or vasopressin (0.01 – 0.08 U/min) – Baseline norepinephrine infusion signficantly reduced in vasopressin group
  • 33. The Evidence• Russell N Engl J Med 2008 – Multicenter, randomized, double-blind trial – 778 patients with septic shock receiving norepi – received either norepinephrine (5-15μg/min) or low-dose vasopressin (0.01-0.03 U/min) – no significant difference in 28-day mortality or rates of serious adverse events – In less severe septic shock (norepi < 15 μg/min), mortality was lower in vasopressin group (26% vs 36%)…
  • 34. Case #370-year-old man collapses at home – v. fib arrest.After full pre-hospital ACLS  asystole on arrival in ED
  • 35. Vasopressin in ACLS• 2010 ACLS guidelines – pulseless arrest (v. fib, v. tach or asystole) – Epinephrine 1 mg IV Q 3 – 5 min, or – Vasopressin 40 U as IV bolus x 1 • to replace first or second dose epi• European recommendation – 1 mg epinephrine  alternate 40 U vasopressin and 1 mg epinephrine Q 3 min Krismer Crit Care Med 2004 (Wenzel, et al. in Austria)
  • 36. The Evidence• Wenzel N Engl J Med 2004- double-blind, prospective, randomized, controlled- compared epinephrine and vasopressin  similar for v. fib. and PEA  vasopressin better for asystole- epinephrine more effective after vasopressin ?
  • 37. Vasopressin in ACLSWenzel N Engl J Med 2004 VasoEpi•% Survival to Hospital Admit – Ventricular fibrillation 46 43 – PEA 33 30 – Asystole 29 20•% Survival to Discharge – Asystole 4.7 1.5
  • 38. The Evidence• Aung Arch Intern Med 2005- meta-analysis of 1519 patients with cardiac arrest from 5 randomized controlled trials- No clear advantage of vasopressin over epi- “ACLS should not recommend vasopressin in resusvitation protocols until more…data”
  • 39. The Evidence• Gueugniaud New Engl J Med 2008 – multicenter randomized trial – 2894 out-of-hospital cardiac arrest patients – epinephrine/vasopressin vs epinephine – combination of drugs was not superior for: • survival to hospital (20.7% vs. 21.3%) • survival to discharge (1.7% vs. 2.3%)
  • 40. Case #448-year-old man with upper GI bleed.PMH: cirrhosisVS: 70/50, 120, 24, 98% O2Despite aggressive Rx  hypotensionpersists
  • 41. Intractable hypotension inlate-phase hemorrhagic shock
  • 42. Vasopressin for irreversible shock69-year-old man in MVA with extensive injury - received crystalloid, colloid, hypertonic saline - hemorrhagic shock  2.5 mg epinephrine - asystole arrest  40 U vasopressin + CPR - v. fibrillation  defib with 200 J - stable BP x 20 minutes (CT and to OR) - retroperitoneal hemorrhage uncontrolledHaas (Wenzel) J Trauma 2004
  • 43. Vasopressin forirreversible shock
  • 44. Vasopressin for irreversible shock• Epinephrine – decreased effectiveness – hypercapnic acidosis – hypoxia• Vasopressin better than epinephrine – better vasopressor during severe acidosis • ? inhibition of nitric oxide vasodilation – blood from muscle, and gut  heart and brain
  • 45. Conclusions• Use norepinephrine, if you need it – Add dobutamine if need inotropic help• Dopamine is rarely enough• When all else fails, try epinephrine• Watch vasopressin