ACUTE PULMONARY EDEMA :

NITRATE OR DIURETIC

Dr. HenyMartini, SpJP(K)

 Epidemiology
¨ Acute Heart Failure (AHF) à clinical syndrome of new or
worsening signs and symptoms of HF (decompensated) often
leading to hospitalization to the Emergency dept.
¨ AHF represents the first reason for hospitalization in
individuals aged 65 years or older in the Western world,
accounting for >1 million hospitalizations per year in the US
¨ AHF represents a period of high risk for patients, with a
20% to 30% mortality rate within 6 months after admission
¨ Most hospitalized patients have significant volume overload
(acute lung edema), and congestive symptoms predominate

1. ESC Text book Intensive and Acute Cardiovascular Care, 2015: AHF epidemiology, classification
2. Meyer TE: Acute Heart Failure and Pulmonary Edema, in Cardiac Intensive Care 2010
ESC Text book Intensive and Acute Cardiovascular Care: AHF epidemiology, classification
 Acute Heart Failure
¨ AHF refers to rapid onset or worsening of symptoms
and/or signs of HF.
¨ It is a life-threatening medical condition requiring
urgent evaluation and treatment, typically leading
to urgent hospital admission.
¨ may present as a first occurrence (de novo) or, more
frequently, as a consequence of acute
decompensation of chronic HF

(ESC) 2016 Guidelines Diagnosis and Treatment on acute and chronic heart failure
 Clinical Presentations of Acute Heart Failure

(ESC) 2008 Guidelines Diagnosis and Treatment on acute and chronic heart failure
Precipitants Factors of Acute Heart Failure
 CARDIOGENIC PULMONARY EDEMA

Defined as pulmonary edema due to increased

capillary hydrostatic pressure secondary to
elevated pulmonary venous pressure

Murray jj 2012, Pulmonary edema: pathophysiology and diagnosis, INT J TUBERC LUNG DIS 15(2):155–160
ACS
PATHOPHYSIOLOGY ACUTE
PULM0NARY EDEMA
PATHOPHYSIOLOGY ACUTE PULMONARY EDEMA

Henson V L: Cardiogenic Pulmonary Edema, Royal collage of Emergency Medicine 2014

Acute Pulmonary Edema, NEJM 2005
 Classification severity of AHF

(ESC) 2008 Guidelines Diagnosis and Treatment on acute and chronic heart failure
Forrester Classification

Cardiac Index
18 mmHg
(L/min/m2)
5 Subset I Subset III
4 (Normal) (Congestion)
Warm and Dry Warm and Wet
3
2.2L/min/m2
2 Subset II Subset IV
(Hypoperfusion) (Congestion and
1 Cold and Dry hypoperfusion)
Cold and Wet
10 20 30
Pulmonary Capillary Wedge Pressure (mmHg) Nohria A et al. JAMA.2002:287; 628-40
 Clinical Presentation of Acute HF

ESC 2016 : Guidelines of Diagnosis and Treatment Chronic and Acute HF

 Differentiation of Noncardiogenic from Cardiogenic
Pulmonary Edema Based on Clinical Data

Meyer TE: Acute Heart Failure and Pulmonary Edema, in Cardiac Intensive Care 2010
 Differentiation Chest Radiographs from Patients with
Cardiogenic and Non-cardiogenic Pulmonary Edema.

ALO Cardiogenic ALO Non- Cardiogenic

Acute Pulmonary Edema, NEJM 2005

Acute Pulmonary Edema, NEJM 2005
 Management of patients with acute heart failure based
on clinical profile during an early phase

ESC 2016 : Guidelines of Diagnosis and Treatment Chronic and Acute HF

(ESC) 2012 Guidelines Diagnosis and Treatment on acute and chronic heart failure
M
• MORPHINE

O
• OXYGEN

Na
• NITRATE

F
• FUROSEMIDE
 Oxygen
¨ Oxygen may be given to treat hypoxaemia (SpO2
< 90%), which is associated with an increased risk
of short-term mortality
¨ Oxygen should not be used routinely in non-
hypoxaemic patients as it causes vasoconstriction
and a reduction in cardiac output

(ESC) 2012 Guidelines Diagnosis and Treatment on acute and chronic heart failure
 Morphin
¨ May be useful in some patients with acute pulmonary
oedema as they reduce anxiety and relieve distress
associated with dyspnoea
¨ Morphin are also thought to be venodilators, reducing
preload, and may also reduce sympathetic drive
¨ Intavenous boluses of morphine 2.5–5 mg may be
administered. This dosing can be repeated as required
¨ Caution in patients with hypotension, bradycardia,
advanced AV block, or CO2 retention
¨ Side effect : nausea and depress respiratory drive,
potentially increasing the need for invasive ventilation

(ESC) 2012 Guidelines Diagnosis and Treatment on acute and chronic heart failure
Guideline Heart Failure ESC 2012
Guideline Heart Failure ESC 2012
 Diuretics
¨ Diuretics are a cornerstone in the treatment of patients
with AHF and signs of fluid overload and congestion
(acute pulmonary edema)
¨ Diuretics increase renal salt and water excretion and
have some vasodilatory effect
¨ In patients with AHF and signs of hypoperfusion,
diuretics should be avoided before adequate perfusion
is attained
¨ The initial approach to congestion management involves
i.v. diuretics with the addition of vasodilators for
dyspnoea relief if blood pressure allows

ESC 2012 & 2016 : Guidelines of Diagnosis and Treatment Chronic and Acute HF
 Diuretics
¨ In patients with resistant peripheral oedema (and ascites), a
combination of a loop and a thiazide (e.g. bendroflumethiazide) or
thiazide-like diuretic (metolazone) may be needed to achieve an
adequate diuresis
¨ However, this combination requires careful monitoring to avoid
hypokalaemia, renal dysfunction and hypovolaemia
¨ The optimum dose and route of administration (bolus or continuous
infusion) are uncertain
¨ DOSE study à compared 12-hourly bolus injection with continuous
infusion and low-dose (equal to pre-existing oral dose) with high
dose (×2.5 times previous oral dose)
¨ the high-dose strategy was associated with greater improvement in
a number of secondary outcomes (including dyspnoea) but at the
expense of more transient worsening of renal function

1. ESC 2012 & 2016 : Guidelines of Diagnosis and Treatment Chronic and Acute HF
2. Felker GM, LeeKL,et al. NEJM 2011 : Diuretic strategies in patients with ADHF
(ESC) 2008 Guidelines Diagnosis and Treatment on acute and chronic heart failure
 Vasodilators (NITRAT)
¨ Intravenous vasodilators are the second most often used
agents in AHF for symptomatic relief
¨ however, there is no robust evidence confirming their
beneficial effects (reduced preload and afterload, increase
stroke volume)
¨ Most useful in patients HTN, and should be avoided in
patients with SBP <90 mmHg
¨ Vasodilators should be used with caution in patients with
significant mitral or aortic stenosis
¨ Nesiritide à a human BNP that acts mainly as a vasodilator
was recently shown to reduce dyspnoea by a small but
statistically significant amount when added to conventional
treatment (mainly diuretic)
1. ESC 2012 & 2016 : Guidelines of Diagnosis and Treatment Chronic and Acute HF
2. Cotter G et al. Lancet 1998 : A RCT oh high dose ISDN plus low dose furosemid in severe pulmonary edema
3. JAMA 2002 : IV nestiride Vs nitroglyserine for treatment decomp congestive HF
 Intravenous Vasodilators Used To Treat Acute
Heart Failure /Acute Pulmonary Edema

(ESC) 2012 Guidelines Diagnosis and Treatment on acute and chronic heart failure
 Action of Nitrates on Circulation

The major effect is on

the venous
capacitance vessels,
with additional
coronary and
peripheral arteriolar
vasodilatory benefit

Opie LH & Horowitz JD. Nitrates and newer antianginals. In: Drugs for the Heart. 7th ed. Saunders Elsevier. China
 Nitrates Mechanism

Effects of nitrates in
generating NO and
stimulating guanylate
cyclase to cause a
vasodilation

Opie LH & Horowitz JD. Nitrates and newer antianginals. In: Drugs for the Heart. 7th ed. Saunders Elsevier. China
Mode of action NTG
release NO- SMC of vessel
NTG NO-

Guanylyl cyclase activation

GTP cGMP
(Guanosine-5'-triphosphate)

Myosin LC –PO4 Myosin LC

Actin

Contraction Relaxation Vasodilation

Nitroglycerin
¨ Mode of action : SMC of vessel relaxation è dilation of
venous, artery and arteriol.
¨ Maximum venodilation occurs at very low plasma
concentration (<0.2 ng ml-1) of nitroglycerin
Arteriol vasodilator
Venodilator
(Max dose)
• Pooling of blood in capacitance vessels • Decrease SVR
• Decrease venous return to RV • Decrease afterload
• Decrease in intracardiac pressures and • Decrese blood pressure
volumes
• Reduction in left ventricular preload
• May cause a decrease in stroke volume
and cardiac output if left ventricular
filling pressure is low..
CLINICAL INDICATION OF NITROGLYCERIN

¨ Acute coronary syndrome

¨ Acute heart failure
¨ Hypertension emergency (crisis hypertension)
 Acute Coronary Syndrome
Algorithm
Ischemic chest pain

Initial management: Immediate check up: (<10 menit)

• oxygen • Vital sign
• Aspirin • ECG
• NTG (sublingual/spray/IV)
• Morphine iv if chest pain still Hasil EKG
persist

Non-ST elevation
Elevation ST
High risk patient
NSTEMI/UAP

Anticoagulan +/- • NTG

reperfusi • Beta-adrenergik receptor
blocker
• Clopidogrel
• Heparin
NTG is used for overcoming chest • Gp IIb/IIa
pain caused by cardiac ischemia
monitoring
DRUGS FOR ACUTE HEART FAILURE
 DRUGS FOR HYPERTENSION EMERGENCY

NTG administration in hypertension emergency caused

by coronary ischemia
ANTIHYPERTENSION TREATMENT FOR CRISIS
HYPERTENSION

NTG was recommended to be combined with other

antihypertension drugs in crisis hypertension with acute lung
edema and acute miocard infarct
Thomas Münzel et al. Circulation. 2011;123:2132-2144
 Pharmacokinetic of Nitroglycerin

¨ Wide distribution
¨ Plasma therapeutic concentration 0,1-3 ng/ml (sd 5
ng/ml)
¨ Nitroglycerin bound 60% plasma protein, metabolit
1,3-glyceryl dinitrate 60%, 1,2-glyceryl dinitrate
30%
¨ Onset of action 1-2 minutes IV
¨ Duration 3-5 minutes
¨ Half time 1-4 minutes

Opie LH & Horowitz JD. Nitrates and newer antianginals. In: Drugs for the Heart. 7th ed. Saunders Elsevier. China
 NTG versus vasodilator

Nicardipine Nitroprusside Nitrogliserin

Class of treatment CCB Vasodilator Vasodilator
Onset ++++ ++++ ++++
Decrease of Afterload ++++ ++++ +
Decrease of Preload 0 ++ ++++
Coronary steal 0 + 0
Coronary vasodilation +++ + ++++
Takicardia + ++ ++
Hypotension + ++ +++
Toxicity of sianida 0 ++++ 0
Easy of using ++++ ++ +++
 Nitroglycerin Vs Isosorbid Dinitrate

Nitroglycerin Isosorbide
Dinitrat
Type of Nitrates Trinitrates Dinitrates
(glyceryl
trinitrates)
Onset Fast: 1 minutes Delayed due to
bioconversion to
mononitrate in liver
Duration 3-5 minutes
Half life 1-4 min 10 mins
Opie LH & Horowitz JD. Nitrates and newer antianginals. In: Drugs for the Heart. 7th ed. Saunders Elsevier. China
 Indication NTG vs ISDN
NTG injection
Indication • NTG is indicated for treatment of
peri-operative hypertension
• for induction of intraoperative
hypertension.
• for control of congestive heart
failure in the setting of acute
myocardial infarction
• for treatment of angina pectoris in
patients who have not responded to
sublingual nitroglycerin and ß-
blockers
ISDN injection
• Severe angina pectoris (e.g. unstable or
vasospastic angina)
• Acute myocardial infarction
• Acute left ventricular failure
• To facilitate or prolong
revascularization procedures and to
prevent or relieve coronary spasm
during percutaneous transluminal
coronary angioplasty (PTCA)
NTG versus ISDN

ISDN was successful in treating hypertension in 63% of the events, whereas

NTG had an 83% success.
THANK YOU

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