1. MANAGEMENT OF PATIENTS ON INOTROPIC SUPPORT OUTSIDE ICU
Sonia Cherian
AHNS DH

2. Objectives: At the end of this session the nurses will be able to:
Define the meaning and types of inotropes
Understand the commonly used inotropes and their effect on human body.
Familiarize with their use in general wards outside ICU
Enlighten on various study implications worldwide
Survey done in DH and efforts made towards improving management of patients on inotrope infusions outside the intensive care areas.
Elaborate on the various nursing implications

3. Introduction:
Inotropic and vasopressor agents have increasingly become a therapeutic cornerstone for the management of several important cardiovascular syndromes.
In broad terms, these substances have excitatory and inhibitory actions on the heart and vascular smooth muscle, as well as important metabolic, central nervous system, and presynaptic autonomic nervous system effects.
They are generally administered with the assumption that short- to medium-term clinical recovery will be facilitated by enhancement of cardiac output (CO) or vascular tone that has been severely compromised by often life- threatening clinical conditions.

4. Definition: What are inotropes?
Inotropic agents, or inotropes, are medicines that change the force of your heart's contractions. : Increases myocardial contractility and cardiac index
There are 2 kinds of inotropes: positive inotropes and negative inotropes.
Positive inotropes strengthen the force of the heartbeat.
Negative inotropes weaken the force of the heartbeat.
Texas heart Institute, July 2015

5. Positive chronotropy Positive inotropy Positive dromotropy
Heart rate is increased
Positive chronotropy
Contractility is increased
Positive inotropy
Conduction of impulse (velocity) is increased
Positive dromotropy
Rate of myocyte relaxation is increased
Positive Lusitropy

6. Purpose:
Improve cardiac output and distribute blood flow appropriately
Reduce symptoms and improve quality of life
Increase organ perfusion
Overall, they function to rapidly correct affected systems through the enhancement of cardiac output (CO) or vascular tone that has been severely compromised by often life-threatening clinical conditions.
CO = SV x HR

7. Positive Inotropes Negative inotropes
Congestive heart failure
Cardiomyopathy
Recent myocardial infarction.
Post heart surgery
Cardiogenic Shock
Negative inotropes
Hypertension,
Chronic heart failure,
Arrhythmias
Angina.
MI patients to reduce stress, prevent further infarctions
Positive inotropes strengthen the heart's contractions, so it can pump more blood with fewer heartbeats.
Negative inotropes weaken the heart's contractions and slow the heart rate. Calcium channel blockers Diltiazem Verapamil Procainamide

8. Indications for Vasopressors and Inotropes
Shock
Congestive heart failure (CHF)
Postoperative support
Forms of Shock*
Hypovolemic shock
Cardiogenic shock
Obstructive shock (extracardiac)
Distributive shock

9. Side effects Low blood pressure (hypotension)
An irregular heartbeat palpitations, sweating, or fainting
blurry eyesight, double vision, or seeing halos around objects
Dizziness or lightheadedness
Headache
A loss of appetite
Vomiting
Fatigue
Diarrhea
Erectile dysfunction
Breast enlargement in men
Decreased sex drive
Skin rash or hives
Eye sensitivity to light
Nosebleeds and bleeding gums 

10. Catecholamines
The most commonly used inotropes are the catecholamines; these can be endogenous (eg, adrenaline, noradrenaline) or synthetic (eg, dobutamine, isoprenaline).
Most catecholamines have a short half-life (about two minutes) and steady-state blood concentrations are reached within 10 minutes. They are therefore usually given by continuous infusion.

11. Location and action of sympathetic or adrenergic receptorsα1
Peripheral, renal and coronary circulation
Vasoconstriction
smooth muscle contraction and an increase in systemic vascular resistance stimulation ß1
Heart
Increase in contractility (inotropic) and heart rate (chronotropic) ß2
Lungs; peripheral and coronary circulation
Vasodilation, bronchodilation
Dopaminergic (D1/D2)
Mesenteric, renal, coronary arteries
Vasodilation (eg:Renal)

12. Forms of Catecholamines
Sympathomimetic amines: Dobutamine and Isoproterenol
Pure alpha agents: Phenylephrine
Mixed alpha and beta receptor agents: Norepinephrine
Mixed alpha and beta receptor effects: Dopamine and Epinephrine

13. Dopamine Low doses (0.5 to 3 μg/kg/min)
Stimulation of dopaminergic D1 receptors in the coronary, renal, mesenteric, and cerebral beds
D2 receptors in vasculature and renal tissues promotes vasodilation and increased blood flow to these tissues.
Low doses (0.5 to 3 μg/kg/min)
Dopamine weakly binds to β1 adrenergic receptors, promoting NE release
Results in increased inotropy and chronotropy, with a mild increase in SVR.
Intermediate doses (3 to 10 μg/kg/min)
α1adrenergic receptor–mediated vasoconstriction dominates
Higher infusion rates (10 to 20 μg/kg/min)

14. Dobutamine Dobutamine is a synthetic catecholamine
With a strong affinity for both β1- and β2-receptors
With its cardiac β1-stimulatory effects,
dobutamine is a potent inotrope, with weaker chronotropic activity.
Despite its mild chronotropic effects at low to medium doses,
Dobutamine significantly increases myocardial oxygen consumption.
This exercise-mimicking phenomenon is the basis for Dobutamine Stress echo tests
At higher infusion rates.
Vasoconstriction progressively dominates
Tolerance can develop after just a few days of therapy and malignant ventricular arrhythmias can be observed at any dose.
This exercise-mimicking phenomenon is the basis upon which dobutamine may be used as a pharmacological stress agent for diagnostic perfusion imaging, but conversely, it may limit its utility in clinical conditions in which induction of ischemia is potentially harmful.

15. Prolonged NE infusion can induce apoptosis of cardiac myocytes.
Norepinephrine, is a potent α1-adrenergic receptor agonist with modest β-agonist activity, which renders it a powerful vasoconstrictor with minimal Inotropic & chronotropic effects
NE primarily increases SVR & CO -systolic pressure, MAP, pulse pressure.
Coronary flow is increased owing to elevated diastolic blood pressure too.
Often used with other inotropes, like Dobutamine to maintain adequate perfusion
Prolonged NE infusion can induce apoptosis of cardiac myocytes.
genetically regulated cell self destruction

16. Phenylephrine
Potent synthetic α-adrenergic activity and virtually no affinity for β-adrenergic receptors - Used primarily as a rapid bolus for immediate correction of sudden severe hypotension.
Used to raise mean arterial pressure (MAP) and has no HR effects.
severe hypotension and concomitant aortic stenosis
the simultaneous ingestion of sildenafil and nitrates
to decrease the outflow tract gradient in patients with obstructive hypertrophic cardiomyopathy
Vagally mediated hypotension during percutaneous diagnostic or therapeutic procedures.

17. Side Effects and Adverse Reactions to Catecholamines
Changes in heart rate
Arrhythmias secondary to increased myocardial oxygen consumption
Hypertension, which may lead to reflex bradycardia (vasoconstrictors)
Reduced cardiac index (high doses)
Hypotension (vasodilators and inotropes)
Myocardial ischemia from increased oxygen demand
Tremors, restlessness, confusion, delirium from nervous system stimulation
Hyperglycemia
Extravasation and subsequent tissue necrosis (beta1 stimulators)
Increased white blood cell count secondary to the autonomic stress response (sympathomimetic amines)

18. Intensive Care Med (2004) 30:1276–1291
Vasopressin
Vasopressin is a potent vasopressor. It causes arterial smooth muscle cell contraction through a non- catecholamine receptor pathway, thus it represents an attractive adjunct for improving organ perfusion during the management of septic shock, especially when catecholamines are ineffective.
Growing evidence suggests that low dose (<0.04 U/min) vasopressin is safe and effective for the treatment of vasodilatory shock.
Side Effects:
Extravasation and subsequent tissue necrosis
Myocardial ischemia
Intensive Care Med (2004) 30:1276–1291

19. KENYATTA NATIONAL HOSPITAL, Nairobi, June 2014
A total of 70 patients recruited in the study. Majority were female patients. Age distribution was from as young as month old to as old as 75yr, this is because there is currently no separate paediatric critical care unit.
Dopamine was the most used inotrope (41.4%) followed by norepinephrine (23.7%). This is comparable to a study on inotropes and vasopressors in Scandinavian intensive care units where dopamine was used most (47%) followed by norepinephrine (40%).
Vasopressin is useful in septic shock that is resistant to dopamine, norepinephrine and epinephrine.
Phenylephrine is the drug of choice in neurogenic shock.
KENYATTA NATIONAL HOSPITAL, Nairobi, June 2014

20. Prospective, observational, cohort study.
SETTING: Intensive care unit of a university hospital.
PATIENTS: Ninety-seven adult patients with septic shock.
The 57 patients who were treated with norepinephrine had significantly lower hospital mortality (62% vs. 82%, p < .001; relative risk = 0.68; 95% confidence interval = ) than the 40 patients treated with vasopressors other than norepinephrine (high-dose dopamine and/or epinephrine).
Results indicate that the use of norepinephrine as part of hemodynamic management may influence outcome favorably in septic shock patients. The data contradict the notion that norepinephrine potentiates end-organ hypoperfusion, thereby contributing to increased mortality.
Martin C, Viviand X, Leone M,Thirion X, ‘Effect of norepinephrine on the outcome of septic shock’ Critical care medicine 2000 Aug;28(8):

21. SURVEY in DH
Objective
To survey the use of vasopressor and inotropic agents over two months at DH.
Study design
An observational, descriptive study.
Setting
General Wards excluding ED, pediatric units and critical units.
Study population
Patients who were initiated on inotrope or vasopressor agent in the above units at DH.
Sample size = 50
Sampling procedure
Convenient sampling was used to select the patients. The eligible patients were recruited consecutively into the study using the inclusion criteria

22. Inclusion Criteria:
Adult patients who were initiated on inotropes/vasopressors in general ward
Exclusion Criteria:
Critical areas (MICU, SICU, CCU, HDMU)
Pediatric units (3E, 4E/4C)
Neonatal ICU
Study Definitions:
Inotropes: Dopamine/Dobutamine/Noradrenaline/Phenylephrine infusions
Basic monitoring: Includes monitoring heart rate, pulse oximeter, central venous pressure and non-invasive blood pressure.
Advanced Monitoring: Includes any of the following - continuous ECG monitoring, Invasive BP monitoring, CO monitoring, PA monitoring

23. Study variables The types of inotropic/vasopressor agents available
Their indications
Modes of haemodynamic monitoring
Techniques used to administer the agents.
Nurses knowledge
Nurses skills

24. Survey Tool: Ward Age Male/Female Type of Inotropes used
Medical
Oncology
Surgical
Others
Age
Male/Female
Type of Inotropes used
Single/Double inotrope used
Indications/Diagnosis
Mode of Access IV/Jugular/Central line
Mode of hemodynamic Monitoring
basic
advanced
Technique of administration
Syringe pumps
Infusion pumps
Side effects if any
Arrhythmias/Hypotension/Extravasation
Nurses views & anxieties
Nurses Knowledge gaps
Nurses Skill gaps

25. Frequency of Inotropic Use outside ICU
38% Medical wards
25% Oncology wards
25% surgical wards
12% Others

26. Results: Age Male/Female Single/Double inotrope used
Most of the patients ranged between the age of 55 to 70 yrs
Male/Female
66 % Male
34% Female
Single/Double inotrope used
Mostly single 92%
8% double
Indications/Diagnosis
The leading cause for initiating inotropes was septic shock - (48.6%).
Mode of Access IV/Jugular/Central line
50% IV
40% External jugular
10% central
Mode of hemodynamic Monitoring
Basic 97%
Advanced 3%
Technique of administration
Syringe pumps
100% Infusion pumps

27. Nor-Epinephrine and Dopamine Nor-Epinephrine and Dobutamine
Results
Leading cause
Septic shock (48.6%)
Septic shock
Nor-Epinephrine and Dopamine
Cardiogenic shock
Nor-Epinephrine and Dobutamine
Mode of hemo-dynamic monitoring
Basic monitoring
Mixed venous sample if low , if Hb low correct that then NE

28. Nurses’ skill & knowledge Gaps
Inotropic effects & toxic effects
Preparation of infusion
Titration of infusions
Hemodynamic monitoring
Nursing Implications

29. Policy formulated: Purpose & Scope Policy statements
Procedure & Responsibility
Preparation & administration (IV line)
Preparation & administration (Central line)
Titration tables (IV Line)
Titration tables (Central line)
The weaning regime. Precautions while ceasing infusion, nursing implications & some salient key points

30. Color coded Titration Tables

31. Nursing Sessions on Nursing Implications
Monitor blood pressure
Monitor pulse and EKG
Monitor blood glucose Continuous Pulse oximetry
Short half life permits for rapid titration
Monitor Fluid intake and output
Monitor labs, serum K levels, detect early signs of impeding arrhythmias
Monitor signs of extravasation, as vasoconstrictors can cause tissue necrosis.
Monitor LOC (restlessness, confusion, delirium)
Short half life and dosage stability in 10 min by infusion, permitting for rapid titration

32. Nursing Implications – key points
Inotropes have an extremely short half-life. Consequently, they can be given only as continuous infusions and should never be stopped abruptly, but should be decreased gradually;
The clinical features of hypotension, tachycardia, oliguria and decreased perfusion can be the result of hypovolaemia, inadequate cardiac function or a combination of both. Before starting inotrope therapy, hypovolaemia must be excluded and if necessary the patient should be fluid resuscitated;
When starting inotrope therapy, the dose should be increased until the desired effect is achieved, as opposed to starting with a high dose and decreasing it until the effect is maintained;
As the drugs are titrated to the effect on blood pressure and perfusion, the method of administration has to be accurate and requires an infusion device and a dedicated infusion line;

33. Key points contd… SV X HR = CO CO X SVR = BP Oxygen Delivery
If peripheral extravasation occurs, can cause local tissue necrosis.
Dilution and peripheral administration may result in the patient receiving an unwanted volume of fluid merely to deliver the drug
When the heart is required to work harder, by increasing contractility and/or heart rate with inotropes, there is increased myocardial oxygen demand.
Maintain arterial oxygen saturations, with respiratory interventions if necessary
Ensure adequate haemoglobin levels to transport the oxygen.
SV X HR = CO
CO X SVR = BP
Oxygen Delivery
Arterial CO
oxygen
content

34. Key points contd…
Blood-pressure monitoring - minimum of non-invasive blood pressure (NIBP) but some patients may require continuous arterial blood-pressure monitoring; Record baseline BP.
The patient’s acceptable cardiovascular parameters (SBP, MAP) are to be documented in the medical records by the doctor.
Observe peripheral perfusion and temperature and level of consciousness; Pulse oximetry (to be used with caution if the patient has reduced peripheral perfusion)
Both dopamine and dobutamine infusions are incompatible with alkaline solutions eg Na HCO3 and many medications e.g. antibiotics.

35. CONCLUSION:
Despite widespread use, the evidence base for the use of inotropes and vasopressors in critically ill patients is limited. Clearly, many patients would not survive without inotropic support, but there is, nonetheless, considerable variation in clinical practice.
Infusions of inotropes should be administered in areas outside ICU in a manner that maximises patient care and minimizes potential complications.
Current practice can be improved through a more detailed understanding of the diverse actions of these agents and the potential toxic effects, formulation of an evidence based policy that is practical in the existing settings

36. REFERENCES:
Practice Guideline ‘Dopamine or Dobutamine Infusions Outside ICU’ Sydney Children’s hospital, December 2014 accessed from
Overgaard C & Dzavik V, Contemporary Reviews in Cardiovascular Medicine -Inotropes and Vasopressors . AHA 2008; 118:
Heart Information Centre, Texas Heart institute, July 2015
Berry W, & McKenzie C, ‘Use of inotropes in critical care’, The Pharmaceutical journal, Jan 2010
Mansoor B, Long M & Pearse R, ‘Use of inotropes and vasopressor agents in critically ill patients’ British journal of pharmacology 165;7, April 2012
Sheppard M. ‘Positive Inotrope Therapy’ Nursing Times April 2001, 97; 17:36
Martin C, Viviand X, Leone M,Thirion X, ‘Effect of norepinephrine on the outcome of septic shock’, Critical care medicine Aug;28(8):
Review and Update on Inotropes and Vasopressors ttp://
Gokhan M, Philip F. Intensive Care Med (2004) 30:1276–1291
Vasopressors and Inotropes Pharmacology

37. REFERENCES contd..
Reynolds I G (2006) “Calculating IV drip rates with confidence” American Nurse Today Available at /6190/6208/0d39b2a0e 79043daa93d29d73cf4681a.pdf Accessed on
Orlando Regional Medical Center [2011]. “Vasopressor and inotrope usage in shock”. Orlando Regional Medical Center: Orlando. Available at d%20Inotropes%20in% 20Shock.pdf Accessed on
Dellinger, R., Levy, M., Carlet, J. et al. [2008]. “Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock”. Crit Care Med. 36, 1,
The American Heritage® New Dictionary of Cultural Literacy, Third EditionCopyright © 2005 by Houghton Mifflin Company.
Davies, N. [2001]. “Administration of inotropes”. Nursing Times. 97, 29, Available at
.%20Evidence%20Based% 20Nursing%20Policy.pdf accessed on