Jennifer & Joshua Chalk Talk 1/17/2014 Go Hawks! Vasopressors Jennifer & Joshua Chalk Talk 1/17/2014 Go 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 6

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

Progression to Late Shock

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*

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

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

Treatment Fluids / Procedures 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 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

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

Vasopressors Norepinephrine Dopamine Epinephrine Vasopressin Phenylephrine

Vasopressors Phenylephrine

Vasopressors

Vasopressors Vasopressin

Receptors

Receptors

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

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

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

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

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 OR NE 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 pressor Subgroup: 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 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

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” 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

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.

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)

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 On Dopamine, Dobutamine Premixed and in PYXIS! Epinephrine, Phenylephrine, Norepinephrine, Vasopressin Mixed by technician after order received in inpatient pharmacy

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

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

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

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

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 –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, 358:877-887. 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