1. Jennifer & Joshua Chalk Talk 1/17/2014 Go Hawks!
Vasopressors
Jennifer & Joshua Chalk Talk
1/17/2014
Go Hawks!

2. Vasopressors
What?
When?
Why?
Wprecautions?

3. Vasopressors

4. Definitions
Pressor: Increases blood pressure by stimulating constriction of blood vessels
Increases vascular tone

5. Definitions Inotrope: Alters force or energy of muscular contractions
Positive: Increases myocardial contractility

6. Definitions
Shock: Inability of oxygen delivery to meet tissue oxygen requirements
Hypovolemia (decreased circulating volume)
Cardiac function impairment (decreased myocardial contractility)
Inappropriate distribution of cardiac output secondary to abnormal vasodilatation 6

8. Pathophysiology Cardiac output Heart Rate Preload Contractility
Sympathetic and Parasympathetic tone
Circulating chatecolamines
Preload
Changes in venous return
Changes in plasma volume
Contractility
Sympathetic tone
Circulating catecholamines

9. Progression to Late Shock

10. Septic Shock Hypotension despite adequate fluid resuscitation
Presence of hypoperfusion or organ dysfunction
Acidosis / alteration in mental status
Sepsis: temp >38°C or <36°C; HR> 90 bpm*
respiratory rate>20 breaths/min, need for mechanical ventilation; WBC 12,000*

11. Hemorrhagic Shock Rapid reduction in blood volume
Heart rate and blood pressure responses can be variable
Vasopressors may be harmful if pt is hypovolemic; Despite improvement in blood pressure, renal blood flow decreases and renal vascular resistance rises

12. Cardiogenic Shock Pump failure
Results when more than 40% of myocardium damaged
Similar circulatory and metabolic changes to hemorrhagic shock

13. Treatment
Fluids / Procedures
DRUGS!
Vasopressors
Inotropes

14. Fluid Requirements
“There is no evidence-based support for one fluid-type over another”(surviving sepsis)
Early fluid administration more important than fluid type
HES/Albumin/Gelatin/LR; Rivers et al

15. Pharmacology

16. Pharmacology Adrenergic System Alpha adrenergic Beta adrenergic
Increases vascular tone
May decrease cardiac output
May decrease regional blood flow (renal, spleen, cutaneous)
Beta adrenergic
Maintains blood flow
May increase cellular metabolism
May decrease immune system

17. Pharmacology Dopaminergic Increases splanchnic and renal perfusion
Facilitates resolution of lung edema
Associated with harmful immunological effects
May decrease prolactin, human growth hormone

18. Vasopressors Norepinephrine Dopamine Epinephrine Vasopressin
Phenylephrine

19. Vasopressors
Phenylephrine

20. Vasopressors

21. Vasopressors
Vasopressin

22. Receptors

23. Receptors

24. Norepinephrine
Historically considered a poor choice in shock due to excessive vasoconstriction and end-organ hypoperfusion
This opinion began to change recently
Benefits: raise arterial pressure and systemic vascular resistance
Maintain cardiac function / improve renal function

25. Dopamine More potential for arrhythmias/increased heart rate
May increase both blood pressures and flow; may be best used in patient with low heart rate and inadequate fluid resuscitation

26. Epinephrine Epi often used as 3rd line after NE and DA failed
Epi always first line in Anaphylactic Shock

27. Vasopressin Vasopressin works on V1,V2,V3 receptors
Increases bp / may improve mortality
May decrease NE requirements
May improve renal function
Avoid in MI; in cardiac ischemia may decrease contractility/lower CO/increase mortality
At doses > 0.04 units/hr may decrease GI blood flow

28. Studies VASST Vasopressin (0.03 un/hr) v. NE in septic shock
No significant difference in mortality at 28 days
Decreased mortality in patients with less severe septic shock (lowest quartile of arterial lactate)
Vaso + corticosteroids decreased mortality v. NE + corticosteroids
Conclusion: May be effective in patients with less severe septic shock already receiving NE

29. Studies Martin: Norepi in Septic Shock 97 patients in septic shock
Dopamine started at 5mcg/kg/min, titrated to 15mcg/kg/min
If hypotension persisted:
DA increased to 25mcg/kg/min OR
NE added at 0.5mcg/kg/min

30. Martin et al
Patients receiving NE had best survival rate on all days of hospital stay (p<0.001)
Mortality strongly associated with high lactate and low urine output
“NE was associated with a highly significant decrease in hospital mortality. The data contradict the notion that norepinephrine potentiates end organ hypoperfusion through excessive vasoconstriction

31. Studies De Backer: Norepi v Dopamine in Shock.
Multicenter study, 1679 patients
DA with 52.5% mortality
NE with 48.5% mortality (p=0.10)
More arrhythmic events with DA (207v102)

32. DeBacker et al
Included Septic (62.2%), Cardiogenic (16.7%), and Hypovolemic (15.7%) shock.
More patients in DA group required 2nd pressor
Subgroup: DA in cardiogenic shock increased mortality significantly (p=0.03)
Conclusion: “This study raised serious concern about the safety of Dopamine”

33. Practical Considerations
Vascular Access
Access to drug
Compatibilities
Titration
Adverse effects

34. Central vs. Peripheral line
Central always preferred
Peripheral
Line
Must flush well
As big as possible
Preferred infusion site = forearm (basilic, cephalic, and median antebrachial)
Caution with dorsum of hand, wrist, feet
Decision: life vs. limb
MD must be aware
Guardrails alert: pressor must go through central line
Override with MD approval documented
Slower titration with obese patients

35. Central vs. Peripheral line
Jean-Damien, R et al. Central or peripheral catheters for initial venous access of ICU patients
Patients randomized: peripheral (N=128) or central access (N=135)
Included epinephrine/norepinephrine doses up ~0.4 mcg/kg/min (for 75 kg patient); Dopamine/dobutamine doses up to 10 mcg/kg/min
Less major complications with central rather than peripheral access (0.64 vs. 1.04, p<0.02)
Majority of complications in PIV group were inability to insert PIV
Subcutaneous diffusion (aka extravasation)
More with peripheral rather than central access
19/128 (~15%) vs. 2/135 (~1.5%)
Average length of stay ~12 days
All patients managed with “observation and conservative management”
Ricard JD, et al. Central or peripheral catheters for initial venous access of ICU patients: a randomized controlled trial. Crit Care Med Sep;41(9):

36. Mechanism(s) of tissue injury
Extravasation
Drug
Effect
Mechanism(s) of tissue injury
Dobutamine
Irritant; Rare reports of vesicant effects
Cytotoxicity, acidic pH
Dopamine, Epinephrine, Phenylephrine Norepinephrine, Vasopressin
Vesicants
Vasoconstriction
Irritants – This type of drugs acts on irritating the vein.  They usually yield out symptoms such as warmth, redness, tenderness, pain at the site of insertion or along the vein. The symptoms last only a short time and do not cause damage to the surrounding tissues.
Vesicants – This type of drugs causes blister to the tissue which is known as the chemical cellulitis. This extravasation reaction can result to excruciating damage to the skin and the severity of the injury may last for days.

37. Extravasation Phentolamine
Short-term alpha-adrenergic blocking activity
Administration →vasodilatation of vascular smooth muscle
Administer ASAP
Infiltrate area of extravasation with phentolamine: 5 mg diluted in 9 mL NS
Should see near immediate effects; otherwise consider additional dose (Max = 10 mg)

38. Getting a Drip Up and On Sequence of events Hypotensive patient
Recognize pressor needed
Physician orders
Order recognized in ORCA
Pharmacy technician makes drip
Pharmacist checks drip
Pharmacy technician tubes drip
Nurse collects from tube station
Nurse starts drip

39. Getting a Drip Up and On Dopamine, Dobutamine
Premixed and in PYXIS!
Epinephrine, Phenylephrine, Norepinephrine, Vasopressin
Mixed by technician after order received in inpatient pharmacy

40. Getting a Drip Up and On
Persistent hypotension → Ask MD if drip should be sent to bedside
Cost to hospital per bag: $1.56 – 7.23
Call pharmacy
Ask for pharmacist STAT (state you are calling from ED)
State patient scenario briefly
Request pharmacy to start making drip
ONLY Physician may give verbal order with U#, drug and dose
Otherwise MD must place order in ORCA before drip is sent
Request pharmacy to notify PSS when drip sent

41. Compatibilities Variable – Call pharmacy
Most likely to be compatible: Epinephrine, dobutamine, dopamine, vasopressin
Maybe: Phenylephrine
Generally not tested: Norepinephrine

42. Titration Starting a drip Switching a patient from OSH MD must order
Generally best to start low and increase
Adverse effects frequently dose related
Switching a patient from OSH
Check patient weight and dosing UNITS
If the same, transition to UW pump and drug
If different:
Call pharmacy to convert
Start in the low to mid range of dosing and titrate

43. Adverse Reactions x High doses x (less) x (contains sulfites)
Epinephrine
Norepinephrine
Dopamine
Dobutamine
Vasopressin
Phenylephrine
Tachycardia x
High doses
Arrhythmias
x (ventricular)
Increased myocardial O2 demand
Decreased perfusion to vital organs
x (less)
Nausea/vomiting
Metabolic acidosis
Hypersensitivity
x (contains sulfites)
Extravasation

44. References
De Backer D et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010;362:
Martin C et al. Effect of norepinephrine on the outcome of shock. Crit Care Med 2000; 28:2758 –2765
Perel A. The initial hemodynamic resuscitation of the septic patient according to Surviving Sepsis Campaign guidelines – does one size fit all? Critical Care 2008, 12:223
Russel J. Vasopressin in the management of septic shock. Critical Care 2011, 15:226
Russell JA, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008, 358:
Ricard JD, et al. Central or peripheral catheters for initial venous access of ICU patients: a randomized controlled trial. Crit Care Med Sep;41(9):