VasopressorsJennifer & Joshua Chalk Talk

1/17/2014Go Hawks!

Vasopressors

What?When?Why?Wprecautions?

Vasopressors

Definitions

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

Definitions

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

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

PathophysiologyCardiac output Heart Rate

Sympathetic and Parasympathetic toneCirculating chatecolamines

Preload Changes in venous returnChanges in plasma volume

ContractilitySympathetic toneCirculating catecholamines

Progression to Late Shock

Septic Shock

Hypotension despite adequate fluid resuscitationPresence 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*

Hemorrhagic Shock

Rapid reduction in blood volumeHeart rate and blood pressure responses can be variableVasopressors may be harmful if pt is hypovolemic; Despite improvement in blood pressure, renal blood flow decreases and renal vascular resistance rises

Cardiogenic Shock

Pump failureResults when more than 40% of myocardium damagedSimilar circulatory and metabolic changes to hemorrhagic shock

Treatment

1. Fluids / Procedures2. DRUGS!

Vasopressors Inotropes

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

Pharmacology

Pharmacology

Adrenergic System Alpha adrenergic

Increases vascular toneMay decrease cardiac outputMay decrease regional blood flow (renal, spleen, cutaneous)

Beta adrenergicMaintains blood flowMay increase cellular metabolismMay decrease immune system

Pharmacology

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

hormone

Vasopressors

NorepinephrineDopamineEpinephrineVasopressinPhenylephrine

Vasopressors

Phenylephrine

Vasopressors

Vasopressors

Vasopressin

Receptors

Receptors

Norepinephrine

Historically considered a poor choice in shock due to excessive vasoconstriction and end-organ hypoperfusionThis opinion began to change recentlyBenefits: raise arterial pressure and systemic vascular resistanceMaintain cardiac function / improve renal function

Dopamine

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

Epinephrine

Epi often used as 3rd line after NE and DA failedEpi always first line in Anaphylactic Shock

Vasopressin

Vasopressin works on V1,V2,V3 receptorsIncreases bp / may improve mortalityMay decrease NE requirementsMay improve renal functionAvoid in MI; in cardiac ischemia may decrease contractility/lower CO/increase mortalityAt doses > 0.04 units/hr may decrease GI blood flow

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

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 ORNE added at 0.5mcg/kg/min

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

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)

DeBacker et al

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

Practical Considerations

• Vascular Access• Access to drug• Compatibilities• Titration• Adverse effects

Central vs. Peripheral lineCentral always preferred Peripheral

LineMust flush wellAs big as possiblePreferred 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

Central vs. Peripheral lineJean-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”

http://emcrit.org/podcasts/peripheral-vasopressors-extravasation/Ricard JD, et al. Central or peripheral catheters for initial venous access of ICU patients: a randomized controlled trial. Crit Care Med. 2013 Sep;41(9):2108-15

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

ExtravasationPhentolamine

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)

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

Getting a Drip Up and OnDopamine, Dobutamine

Premixed and in PYXIS!

Epinephrine, Phenylephrine, Norepinephrine, Vasopressin

Mixed by technician after order received in inpatient pharmacy

Getting a Drip Up and OnPersistent 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 doseOtherwise MD must place order in ORCA before drip is sent

Request pharmacy to notify PSS when drip sent

Compatibilities

Variable – Call pharmacyMost likely to be compatible: Epinephrine, dobutamine, dopamine, vasopressin

Maybe: Phenylephrine

Generally not tested: Norepinephrine

Titration

Starting a drip 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 drugIf different:

Call pharmacy to convert Start in the low to mid range of dosing and titrate

Adverse Reactions

Epinephrine Norepinephrine Dopamine Dobutamine VasopressinPhenylephrine

Tachycardia x High doses xArrhythmias x High doses x x (ventricular)Increased myocardial O2 demand x x xDecreased perfusion to vital organs x x x (less) xNausea/vomiting x xMetabolic acidosis x x

Hypersensitivity

x (contains sulfites)

Extravasation x x x x x x

References

De Backer D et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010;362:779-89.Martin C et al. Effect of norepinephrine on the outcome of shock. Crit Care Med 2000; 28:2758 –2765Perel A. The initial hemodynamic resuscitation of the septic patient according to Surviving Sepsis Campaign guidelines – does one size fit all? Critical Care 2008, 12:223Russel J. Vasopressin in the management of septic shock. Critical Care 2011, 15:226Russell JA, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008, 358:877-887.Ricard JD, et al. Central or peripheral catheters for initial venous access of ICU patients: a randomized controlled trial. Crit Care Med. 2013 Sep;41(9):2108-15