INOTROPES

+
ELECTROLYTE
IMBALANCE
Presented by: Asya Ameen
INOTROPES
 INOTROPIC EFFECT = CONTRACTILITY
CHRONOTROPIC EFFECT = HEART RATE/RHYTHM
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 ISOPROTERENOL

Primarily an inotropic and chronotropic agent rather than a vasopressor.

It acts upon beta-1 adrenergic receptors and has a prominent chronotropic effect.

The drug's high affinity for the beta -2 adrenergic receptor causes vasodilation and a
decrease in MAP.

Therefore, its utility in hypotensive patients is limited to situations in which hypotension

results from bradycardia.

Adverse effects: similar to epinephrine.

 DOBUTAMINE

Not a vasopressor but rather is an inotrope that causes vasodilation.

Dobutamine's predominant beta -1 adrenergic receptor effect increases inotropy and

chronotropy and reduces left ventricular filling pressure.

The net effect of its minimal alpha -1 and beta-2 adrenergic receptor is increased CO, with
decreased SVR with or without a small reduction in blood pressure.

It used most frequently in severe, medically refractory heart failure and cardiogenic shock
and should not be routinely used in sepsis because of the risk of hypotension.

Adverse effects: similar to epinephrine, in addition, it increases AV conduction, thus, should

be used with cation on Afib .
 DOPAMINE

This drug is dose dependent . It is most often used as a second -line alternative to
norepinephrine in patients with absolute or relative bradycardia and a low risk of
tachyarrhythmias.

At doses < 5 mcg/kg per minute, acts predominantly on dopamine -1 receptors in the renal,
mesenteric, cerebral, and coronary beds, resulting in selective vasodilation.

At 5 to 10 mcg/kg per minute, stimulates beta-1 adrenergic receptors and increases cardiac
output.

At doses >10 mcg/kg per minute, stimulates alpha -adrenergic receptors and produce
vasoconstriction with an increased SVR.

Adverse effects: sympathetic stimulation, in addition to nausea, hypertension and arrhythmia.

 EPINEPHRINE

Has potent beta-1 adrenergic receptor activity and moderate beta-2 and alpha-1 adrenergic
receptor effects.
Clinically, low doses of epinephrine increase CO because of the beta -1 adrenergic receptor
inotropic and chronotropic effects, while the alpha -adrenergic receptor -induced vasoconstriction
is often offset by the beta -2 adrenergic receptor vasodilation. The result is an increased CO, with
decreased SVR and variable effects on the MAP. However, at higher doses the alpha -adrenergic
receptor effect predominates, producing increased SVR in addition to an increased CO.
Epinephrine is most often used for the treatment of anaphylaxis, and as a second line in septic
shock.
Adverse effects: CNS disturbances, anxiety, fear tension, headache and tremor , cerebral
hemorrhage (because it increases blood pressure), Cardiac dysrhythmias, splanchnic
vasoconstriction and Pulmonary edema.
 NOREPINEPHRINE

Acts on both alpha-1 and beta-1 adrenergic receptors, thus producing potent
vasoconstriction as well as a modest increase in cardiac output.

A reflex bradycardia usually occurs in response to the increased mean arterial pressure
(MAP), such that the mild chronotropic effect is canceled out and the heart rate remains
unchanged or even decreases slightly.

Norepinephrine is the preferred vasopressor for the treatment of septic shock.

Adverse effects: Similar to epinephrine, in addition, norepinephrine is potent

vasoconstrictor, if extravasation occurs , it can cause tissue necrosis.
 PHENYLEPHRINE

Purely alpha-adrenergic agonist activity and therefore results in vasoconstriction with

minimal cardiac inotropy or chronotropy. MAP is augmented by raising systemic vascular
resistance (SVR).

The drug is useful in the setting of hypotension with low SVR (e.g., hyperdynamic sepsis,
neurologic disorders, anesthesia -induced hypotension).

A potential disadvantage of phenylephrine is that it may decrease stroke volume, so it is

reserved for patients in whom norepinephrine is contraindicated due to arrhythmias or who
have failed other therapies.

Adverse effects: Large doses can cause hypertension and cardiac irregularities.
 ELECTROLYTE
DISTURBANCES
HYPONATREMIA
h yponatremia: serum
[N a+] < 135 mmol/L
 Concentration of [Na+] in Common Infuses

• [Na+] in 0.45% NaCl = 77 mmol/L

• [Na+] in 0.9% NaCl = 154 mmol/L

• [Na+] in 3% NaCl = 513 mmol/L

• [Na+] in 5% NaCl = 855 mmol/L

• [Na+] in Ringer ’s lactate = 130 mmol/L

• [Na+] in D5W = 0
 Important points

• hyponatremia and hypernatremia are disorders of water balance.

■ hyponatremia = too much water in the ECF relative to Na+ content

■ hypernatremia = too little water in the ECF relative to Na+ content

• solutes (Na+, K+, glucose) that cannot freely traverse the plasma membrane contribute to effective
osmolality and induce transcellular shifts of water

■ Increased ECF osmolality → water moves out of cells. (volume expansion)

■ Decreased ECF osmolality → water moves into cells. (volume contraction)

clinical signs and symptoms of hyponatremia and hypernatremia are secondary to cells (especially
brain cells) shrinking (hypernatremia) or swelling (hyponatremia)
Corrected sodium (mmol/L) = measured sodium (mmol/L) + 0.024 {(glucose [mmol/L] × 18)-100}.
 Signs & Symptoms

• depend on degree of hyponatremia and more importantly, velocity of progression

from onset

• hyponatremia = swollen cells

• neurologic symptoms predominate (secondary to cerebral edema): headache,

nausea, malaise, lethargy, weakness, muscle cramps, anorexia, somnolence,
disorientation, personality changes, depressed reflexes, decreased LOC.

• acute hyponatremia (<24-48 h) more likely to be symptomatic

• chronic hyponatremia (> 24-48 h) less likely to be symptomatic due to adaptation

 Complication

seizures, coma, respiratory arrest, permanent brain damage, brainstem herniation,

death.

• risk of brain cell shrinkage with rapid correction of hyponatremia

■ can develop osmotic demyelination of pontine and extrapontine neurons; may be

irreversible (e.g. central pontine myelinolysis)

■ symptom onset may be delayed 2-6 d; begins as dysarthria, dysphagia, paresis,

movement disorders

→ later on, seizures, lethargy, confusion, disorientation, obtundation, coma

 Treatment

Four important goals:

• prevent further declines in the serum sodium concentration,

• to prevent brain herniation,

• to relieve symptoms of hyponatremia, and

• to avoid overcorrection of hyponatremia in patients at risk for osmotic

demyelination syndrome
Acute onset (<48 hours)

Symptomatic (Acute or Chronic) Asymptomatic

correct rapidly with 100 mL bolus
of hypertonic 3% NaCl.
followed, if symptoms persist, with
up to two additional 100 mL doses
(to a total dose of 300 mL); each
bolus is infused over 10 minutes.
treat with a 50 mL bolus of
hypertonic 3% NaCl, to prevent
further deterioration in serum
sodium
• do not give 3% NaCl if
hyponatremia is autocorrecting
due to water diuresis

The goal of therapy is to rapidly increase the serum sodium by 4 to 6 mEq/L

over few hours, This should generally alleviate symptoms and prevent
herniation.
Chronic onset (≥48 hours)

Specific treatment depends on the volume status of the patient and the
underlying cause.
Hypervolemia & euvolemia Hypovolemia
- Fluid restriction to <1 L/day Isotonic intravenous fluids (e.g.,
fluid intake. normal saline 0.9% or a balanced
- Diuresis (in hypervolemia) solution such as lactated Ringer's
solution)
If fluid restriction fails:
- vasopressin receptor 2
antagonists (e.g. tolvaptan)
- oral urea (osmotic aquaresis)
A rate of <8 mmol/L/day is recommended to prevent myelinolysis.
Treatment of Overly-
Rapid Correction

• give water (IV D5W)

• give ADH to stop water diuresis

(DDAVP 1-2 μg IV)
HYPERNATREMIA
h y p ernatremia: seru m
[N a+] > 145 mmol/L
 DILUTED URINE

REMEMBER: WHEN TREATING HYPONATREMIA, WE CAN

OVERCORRECT AND SHIFT THE PATIENT TO HYPERNATREMIA.
VERY CONCENTRATED
URINE, (APPROPRIATE DILUTED URINE
RESPONSE TO
DEHYDRATION)

REMEMBER: WHEN TREATING HYPONATREMIA, WE CAN

OVERCORRECT AND SHIFT THE PATIENT TO HYPERNATREMIA.
 Signs & Symptoms

hypernatremia = shrunken cells

• acute hypernatremia (<24-48 h) & chronic hypernatremia (> 24-48 h),

• symptoms due to brain cell shrinkage: altered mental status, weakness,

neuromuscular irritability, focal neurologic deficits, seizures, coma, death

• ± polyuria, thirst, signs of hypovolemia

nearly all cases of hypernatremia will be due to chronic hypernatremia

acute hypernatremia primarily presents in patients with diabetes insipidus

 Complication

• Brain shrinkage induced by hypernatremia can cause vascular rupture, with

cerebral bleeding, subarachnoid hemorrhage, and permanent neurologic damage
or death.

• patients with prolonged hyperosmolality, aggressive treatment with hypotonic

fluids may cause cerebral edema, which can lead to coma, convulsions, and death

• osmotic demyelination syndrome may result from hyperosmolar hyperglycemia or

acute hypernatremia.
 Treatment

Correction of hypernatremia requires the administration of dilute fluids to both

correct the water deficit and replace ongoing water losses and, also, when
appropriate, interventions to limit further water loss.
Acute onset (< 48 hours)

• D 5 W i n t rav e n o u s l y, a t a ra t e o f 3 t o 6 m L / k g / h o u r.

• O n c e t h e s e r u m s o d i u m c o n c e n t ra t i o n h a s re a c h e d 1 4 5 m Eq / L , t h e ra t e o f i n f u s i o n i s re d u c e d t o 1
m L / k g / h o u r a n d c o n t i n u e d u n t i l a n o r m a l s e r u m s o d i u m ( 1 4 0 m Eq / L ) i s re s t o re d .

• T h e g o a l o f t h i s re g i m e n i s t o l o w e r t h e s e r u m s o d i u m b y 1 t o 2 m Eq / L p e r h o u r a n d t o re s t o re a
n o r m a l s e r u m s o d i u m i n l e s s t h a n 2 4 h o u rs .

• I f hy p o v o l e m i a a n d hy p e rg l y c e m i a p re s e n t , w i t h o n g o i n g l o s s e s o f s o d i u m a n d w a t e r d u e t o g l y c o s u r i a ,
f re e w a t e r i s u s u a l l y a d m i n i s t e re d a s 0 . 4 5 % N S ra t h e r t h a n D 5 W; i n f u s i o n o f 0 . 4 5 % N S a t 6 t o 1 2 m L / k g
p e r h o u r w i l l p ro v i d e t h e s a m e a m o u n t o f e l e c t ro l y t e - f re e w a t e r a s 3 t o 6 m L / k g p e r h o u r o f D 5 W.

• C o r re c t i o n o f hy p e rg l y c e m i a a n d hy p o v o l e m i a i n c re a s e s t h e s e r u m s o d i u m c o n c e n t ra t i o n b e c a u s e
w a t e r s h i f t s i n t o c e l l s a s hy p e rg l y c e m i a re s o l v e s a n d b e c a u s e w a t e r i s e x c re t e d i n u r i n e w i t h e x c e s s
g l u c o s e . I n p a t i e n t s w i t h s e v e re hy p e rg l y c e m i a w h o s e s e r u m s o d i u m c o n c e n t ra t i o n i s n o r m a l o r h i g h
o n p re s e n t a t i o n , s e v e re hy p e r n a t re m i a i s l i ke l y t o e m e rg e d u r i n g t h e c o u rs e o f t h e ra p y.
Chronic onset (≥ 48 hours)

• D5W intravenously, at a rate of (approximately 1.35 mL/hour x patient's

weight in kg) or approximately 70 mL/hour in a 50 kg patient and 100
mL/hour in a 70 kg patient.

• The goal of water repletion in patients with chronic hypernatremia is to

lower the serum sodium by approximately 10 mEq/L in 24 hours but to
avoid correcting the serum sodium by more than 12 mEq/L in 24 hours.

• To achieve the target rate of correction when ongoing losses are present,
the fluid repletion regimen must also consider replacement of ongoing
free water losses.
HYPERKALEMIA

seru m [K+] > 5.0 m Eq/L

 Signs & Symptoms

• usually asy mptomatic but may develop nausea, palpitations, muscle weakness, muscle stiffness,

• paresthes ia, areflexia, as c ending paralys is , and hy poventilation

• impaired renal ammoniagenesis and metabolic acidosis

ECG c hanges and cardiotoxic ity ( do not correlate well with serum [K+])

• peaked and narrow T waves

• dec reas ed amplitude and eventual los s of P waves

• prolonged P R inter val

• widening of QRS and eventual merging with T wave (sine -wave pattern)

• AV bloc k

• ventricular fibrillation, asystole

 Treatment

• C alcium gluconate 1-2 amps (10 mL of 10% solution) IV, onset within minutes and lasts 30-60
min.

• regular insulin 10-20 units IV, with 1-2 amp D50W, onset of action 15-30 min and lasts 1-2 h.

• NaHCO 3 1-3 ampules (given in 1 L D 5W), ons et of action 15-30 min, transient effect, drives K+
into cells in exchange for H+, effective if patient has metabolic acidosis

• β2-agonist (Ventolin) in nebulized form (dos e = 2 cc or 10 mg inhaled) or 0.5 mg IV, onset of

action 30-90 min, stimulates Na+/K+ ATPase

• furos emide ( ≥40 mg IV), may need IV NS to avoid hy povolemia

• cation-exchange resins: calcium resonium or sodium polysty rene sulfonate (Kayexalate)

• dialys is (renal failure, life threatening hy perkalemia unresponsive to therapy )

 Goals of therapy

• Heart stabilization

• Shift K+ into cells

• Enhance K+ removal via urine or GIT.

C BIG K DROP
C – Calcium gluconate

BIG – β-agonist, Bicarbonate, Insulin, Glucose

K – Kayexalate

DROP – Diuretics, Dialysis

HYPOKALEMIA
serum [K+] < 3.5 mEq/L
URINE K+ < 20
MMOL/L URINE K+ > 20
MMOL/L
 Signs & Symptoms

us ua lly a sympto m a t ic , pa rtic u la rl y whe n mild ( 3. 0- 3. 5 mmo l/L)

• na us e a /vo m i t i n g , fatigue , ge ne ra lize d we a kne s s , mya lgia , mus c le c ra mps , a nd c o nstipat io n. if s e ve re :

a rrhyt hm ia s , rha bdo myo l ys is , myo glo bi n u r ia , a nd ra re ly pa ra lys is with e ve ntu a l re s pira to ry impa irme nt

ECG c ha nge s a re m o re pre dic ti ve o f c linic a l pic ture tha n s e rum [ K + ]

• U wave s mo st impo rta nt ( lo w a mplit u de wave fo llo wing a T wave )

• f latte ne d o r inve r te d T wave s

• de pre s s e d S T s e gme nt

• pro lo nga t io n o f Q - T inte r va l

• s inus bra dyc a rdi a

with s e ve re hypo ka l e m ia : P - R pro lo nga t io n , wide Q RS a nd a rrhyth m ia s ; c o mmo n a rrhyth m ia s s e e n with

hypo ka le mi a : ve ntric u la r f ibrill a t io n , ve ntric u la r ta c hyc a rdi a
 Goals of therapy

• to prevent or treat life-threatening complications (arrhythmias, paralysis,

rhabdomyolysis, and diaphragmatic weakness),

• to replace the potassium deficit, and

• to diagnose and correct the underlying cause.

The urgency of therapy depends upon the severity of hypokalemia, associated

and/or comorbid conditions, and the rate of decline in serum potassium
concentration.

The risk of arrhythmia from hypokalemia is highest in older patients, patients with
organic heart disease, and patients on digoxin or antiarrhythmic drugs
 Chronic onset (≥48 hours)

Treat underlying cause, restore Mg 2+ before correcting K+.

Mild to moderate hypokalemia Symptomatic or severe Hypokalemia

(serum potassium 3.0 to 3.4 (serum potassium 2.5 to 3.0 mEq/L)
mEq/L) - KCL administered orally in doses of 40 mEq, 3-4
oral administration of 10 to 20 times per day or 20 mEq particularly in
mEq of potassium given two to - patients treated with intravenously, every 2-3
four times per day (20 to 80 hours.
mEq/day) - Intravenously in non-dextrose saline solutions.
- max 40 mmol/L via peripheral vein, 60 mmol/L via
central vein, max infusion 20 mmol/h.

Usage of ACE inhibitor or ARB for CHF (reduces angiotensin II action and therefore
reduces aldosterone production)
HYPERCALCEMIA
total corrected serum Ca 2+ > 2.6 mmol/L OR
ionized Ca2+ > 1.35 mmol/L
Symptoms depend on the absolute Ca2+ value and
the rate of its rise (may be asymptomatic)
Treatment
Asymptomatic or Mild
hypercalcemia
asymptomatic or mildly
symptomatic hypercalcemia (3
mmol/L) do not require immediate
treatment.
monitor and avoid: thiazide,
volume depletion, high Ca2+ diet,
lithium and bed rest
Moderate hypercalcemia
Asymptomatic or mildly
symptomatic individuals with
chronic moderate hypercalcemia
(3 to 3.5 mmol/L) may not require
immediate therapy. However, IV
hydration is suitable. And same
precautions described for mild
hypercalcemia are applied.
Severe hypercalcemia
 HYPOCALCEMIA
total correct ed seru m Ca 2+ < 2.2
mmol/L or i on ized cal cium l e v el l ess
t han 1.0 m m ol/L
 Treatment

Rapidity of treatment depends on severity of symptoms and serum calcium level

• mild, asymptomatic, calcium supplementation (elemental calcium 1 g then 500 mg PO

TID)

• severe and/or symptomatic (MEDICAL EMERGENCY)

IV calcium gluconate 1-2 g over 10-20 min, followed by slow infusion Ca 2+ IV drip at 1-2
mg /kg /h

✓ vitamin D replacement, needed for GI absorption of calcium; use 1,25 vitamin D If PTH
level low

✓ treat concurrent hypomagnesemia or calcium will not normalize

RECOURSES:
- UP TO DATE
- BMJ BEST PRACTICE
- TORONTO NOTE 2021
- LIPPINCOTT PHARMACOLOGY

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