Global trends of neonatal, infant and child mortality

Global trends of neonatal, infant and child mortality: implications for child survival
By:Dr KANUPRIYA CHATURVEDI & Dr S.K CHATURVEDI

When are child deaths occurring?

What are under-fives dying of?
(excluding neonatal causes of death)

* Pneumonia
* Diarrhoea
* Malaria
* Measles
* HIV/AIDS

Malnutrition contributes to more than half of all under-five deaths
What are neonates dying of?
* Preterm births
* Severe infection
* Asphyxia
* Congenital anomalies
* Tetanus

INDIA’S SHARE OF GLOBAL BURDEN
SOLUTIONS EXIST

* A mix of community and facility-based interventions
* A mix of integrated child health approaches
* Integrated management of neonatal and child hood illnesses is proven tool

Goals of IMNCI
* Standardized case management of sick newborns and children
* Focus on the most common causes of mortality
* Nutrition assessment and counselling for all sick infants and children
* Home care for newborns to
o promote exclusive breastfeeding
o prevent hypothermia
o improve illness recognition & timely care seeking

Essential components of IMNCI
* Improve health and nutrition workers’ skills
* Improve health systems
* Improve family and community practices
Home visits for young infants: Schedule
Colour Coded Case Management Strategy
Other innovations in case
Innovations in therapy
* Single daily dose gentamycin
* How to treat at home when hospital admission is not feasible
* Counselling the mother to give oral drugs at home
* Clear recommendations for follow up
* Negotiated feeding counselling
What does IMNCI not provide at all or fully
* Antenatal care
* Skilled birth attendance
* Birth asphyxia management
* Improved health system management
* What can be rapidly added to IMNCI
* Inpatient care modules for first level referral hospitals
IMNCI Experience--Milestones
* Early 2002, GOI constituted an Adaptation Group
* In joint GOI-UNICEF review meeting in April 2002 GOI requested to experiment IMNCI in BDCS districts
* July 2002, First national 2 days planning meeting
* December 2002, pre-tested 8-days physician course material
* Early 2003 - adaptation of H&N workers module
* May 2003 – First field testing in Osmanabad followed by one in Shivpuri & content & methodology frozen
* Implementation started in Andoor PHC, Osmanabad in June 03 followed by Valsad district
* Follow-up training of supervisors in April 04 in Osmanabad
* Field trial for case registers initiated in late 2004
* Physicians courses from 2005 included community visit, facilitation technique and briefing on Health workers’ course
* First Facilitation technique course in Orissa in June 2005

Training Flow
Training: Strengths -- Contents Doable
Training Limitations: Contents
Key messages

* Maternal and newborn care and support is essential to achieve a substantial reduction in neonatal mortality
* Improving child survival requires coordinated action between maternal and child health, and other programme areas (e.g. EPI, NUT, RBM, HIV)
* IMCI is an effective delivery strategy for multiple child survival interventions (India has already incorporated newborn care)
* For substantive impact, strong community component must accompany the health system strengthening

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Angioedema

Angioedema

Overview
* Self-Limited, subcutaneous edema resulting from increased vascular permeability
* Generally resolves over 24-48 hours
* Mast Cell / Kinin related etiologies
* Involvement of the lips, pharynx and bowel common (potentially life-threatening)
* Treated with CCS and H1/H2 blockers

Etiology
* Immunologic / IgE mediated
* Hereditary and Acquired (non-mast cell)
Ace-Inhibitors
* ACE (Kininase II) degrades bradykinin
* ACE-I results in inc levels bradykinin
* Pts with genetic deficiencies in bradykinin degradation could be at higher risk
* 0.1-0.7% of patients tx with ACE-I
* Intestinal edema may develop

ACE-I
Hereditary/Acquired
* Kinin-mediated angioedema that may be unmasked with use of ACE-I
* C1-Inh deficiency (level or fx) - Inc BKinin
Summary

* Angioedema is potentially life-threatening
* Associated pruritis and hives points to anaphylaxis
* Absence of pruritis and hives think ACE-I and/or C1-Inh deficiency
* Use caution when switching from an ACE-I to an ARB

Angioedema

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Congestive Heart Failure

Congestive Heart Failure
By:Chris Hague, PhD
Technical Advisor: Seth Goldenberg, PhD

Outline

1. What is congestive heart failure?
2. Cardiac Glycosides
3. Phosphodiesterase inhibitors
4. Beta-adrenergic receptor antagonists
5. Sympathomimetics
6. ACE inhibitors/angiotensin receptor antagonists
7. Vasodilators
8. Diuretics
9. Aldosterone antagonists

Congestive Heart Failure
Patient Classification
* Class I (asymptomatic)
* Class II (mild)
* Class III (moderate)
* Class IV (severe)

Factors contributing to CHF
* Ischemic Heart Disease: most prevalent
* CAD: less blood flow to heart, increased damage
* Myocardial Infarct: damaged tissue
* Hypertension: “overworked” heart
* Diabetes
* Lung Disease
* Cardiomyopathies: heart muscle disease
o dilated - enlarged chambers (ventricle/atria)
o hypertrophic - thickened ventricle walls
* Abnormal heart valves: inefficient pumping
o causes are genetic, infection or disease
* Congenital heart defects: present at birth
* Severe Anemia
* Hyperthyroidism
* Cardiac Arrhythmia

Effect on Cardiac Output
Overall decrease in Frank-Starling curve with CHF
Examples of CHF factors
Hypertrophic Cardiomyopathy
Congenital Heart Defects
Types of Heart Failure

* include left, right or both sides
* left ventricular heart failure
* right ventricular heart failure
Onset of disease

* chronic disease: can take years to develop
* endogenous compensatory mechanisms

Compensatory Mechanisms
Symptoms of CHF
* shortness of breath
* persistent coughing/wheezing
* edema (or excess fluid buildup in body tissues)

Symptoms of CHF
* tiredness/fatigue
* lack of appetite/nausea
* confusion/impaired thinking
* increased heart rate

Problems
* Reduced force of contraction
* Decreased cardiac output
* Increased TPR
* Inadequate organ perfusion
* Development of edema
* Decreased exercise tolerance
* Ischemic heart disease
* Sudden death

Therapeutic Overview
Goals
* alleviate symptoms
* improve quality of life
* arrest cardiac remodeling
* prevent sudden death
Drug
* Chronic heart failure
o ACE inhibitors
o Beta-blockers
o ATII antagonists
o aldosterone antagonists
o digoxin
o diuretics
* Acute heart failure
o diuretics
o PDE inhibitors
o vasodilators

Therapies
Non-drug
* Reduce cardiac work
* Rest
* Weight loss
* low Na+ diet
Cardiac Glycosides
* discovered by William Withering
* published “An Account of Foxglove and some of Its Medical Uses” in 1785
* Foxglove plant
Cardiac Glycosides
* derived from plants
o Strophanus - Ouabain
o Digitalis lanata - Digoxin, Digitoxin
* increase force of myocardial contraction
* alters electrophysiological properties
* toxic side-effects
* Digoxin most common used in USA

Digitalis lanata
Mechanism of Action
* inhibitor of Na+/K+ ATPase pump
* increased [Na+]i
* increased Ca2+ influx through Na+/Ca2+ exchanger
* new Ca2+ steady-state: increased Ca2+ release during cardiac action potential
Electrophysiological Effects
* Direct effects
o spontaneous depolarization of atrial cardiomyocytes at high doses

Electrophysiological Effects
Overall Effect on Cardiac Function

Foxglove
Therapeutic Uses
* only orally effective inotropic agent approved in US
* also for CHF secondary to ischemic heart disease
* contraindicated in patients with Wolff-Parkinson-White syndrome
* does not stop disease progression or prolong life in CHF patients

Pharmacokinetics
* long half-life (24-36 h): once daily dosing
* high bioavailability from oral dosing
* large volume of distribution
* digoxin excreted in kidneys
* digitoxin metabolized in liver, active metabolites
* intestinal flora cause variations in toxicity

Side Effects
* extremely low therapeutic index (~2)
* most effects caused by inhibition of Na+/K+ ATPase in extracardiac tissues
* CNS: malaise, confusion, depression, vertigo, vision
* GI: anorexia, nausea, intestinal cramping, diarrhea
* Cardiac: bradycardia, arrhythmias
* anti-digoxin antibody in toxic emergencies

Serum Electrolytes affect Toxicity
* Ca2+
* hypercalcemia: increases toxicity
* K+
* digitalis competes for K+ binding site on Na+/K+ ATPase
* contraindicated with K+ depleting diuretics or patients with hypo/hyperkalemia
* hypokalemia: increased toxicity
* hyperkalemia: decrease toxicity

Example of cardiac side effects
* action potential recordings from purkinje fiber cells
* toxic doses produce oscillatory after depolorizations
* leads to ventricular tachycardia (C)

Vision Effects
* yellow-tinted vision or yellow corona-like spots

Phosphodiesterase Inhibitors
* primarily used for management of acute heart failure
* positive inotropic effects
* increase rate of myocardial relaxation
* decrease total peripheral resistance and afterload

Mechanism of Action
* inhibitor of type III cAMP phosphodiesterase
* increased [cAMP]
* increased PKA phosphorylation of Ca2+ channels in cardiac muscle
* increased cardiac contraction
* relaxes vascular smooth muscle

Therapeutic Use
* Amrinone (Inocor) and Milrinone (Primacor)
* administered IV
* milrinone is ~1o fold more potent
* T 1/2 = 2.5 h for amrinone and 30-60 min for milrinone
* effective in patients taking Beta-blockers
* does not stop disease progression or prolong life in CHF patients
* prescribed to patients non-responsive to other therapies

Side Effects
* sudden death secondary to ventricular arrhythmia
* hypotension
* thrombocytopenia
* long term clinical trials associated with increased adverse effects and increased mortality
* now only prescribed for acute cardiac decompensation in patients non-responsive to diuretics or digoxin

β-adrenergic receptor antagonists
* “β-blockers”
* standard therapy for treatment of CHF
* cheap!
* reduce sudden death caused by other drugs
* Propranolol: prototype
* Carvedilol: combination effects

Propranolol
Carvedilol
Mechanism of Action
* mechanism still unclear
* antagonizes β-adrenergic receptors on cardiac myocytes
* counterbalances increased SNS activity in CHF
* prevents development of arrhythmias
* reduces cardiac remodeling
* prevents renin release

Therapeutic Use
* administered orally
* usually given in conjunction with other therapy
* effective in patients with chronic systolic heart failure in Class II (mild) to Class III (moderate)
* prevents remodeling and cardiac damage

Side Effects
* cardiac decompensation
* bradycardia
* hypoglycemia
* cold extremeties
* fluid retention
* fatigue

Direct acting sympathomimetics
* cause immediate increases in cardiac inotropy
* goal: to increase cardiac output but not effect total peripheral resistance
* used in treatment of acute life-threatening CHF

Dopamine
Dobutamine
Mechanism of Action
* Norepinephrine/epinephrine: increase CO, increase TPR
* Dopamine:
* Dobutamine:

Therapeutic Use
* administered IV, very short T 1/2
* Dopamine
o used in cardiogenic, traumatic or hypovolemic shock
o used with furosemide in diuretic resistant patients (volume overload)
* Dobutamine
o used in patients with low cardiac output and increased left ventricular end-diastolic pressure
o not for use in hypotensive patients

Side Effects
* restlessness
* tremor
* headache
* cerebral hemorrhage
* cardiac arrhythmias
* used with caution in patients taking β-blockers
* can develop dobutamine tolerance

ACE inhibitors/AT1 receptor antagonists
* Goal: to reduce afterload/preload, reduce workload on heart
* generates positive cardiac inotropy
* used in treatment of chronic CHF

ACE inhibitors/AT1 receptor antagonists
* orally active
* ACE inhibitors
* Captopril
* Enalopril
* AT1 antagonists
* Losartan
* Valsartan

Mechanism of Action
* ACE inhibitors
* AT1 receptor antagonists
* selectively inhibits ATI receptor activation
* decreased preload
* decreased afterload
* decreased cardiac remodeling
* decreased SNS effects

Therapeutic Uses
* drugs of choice in heart failure
* increase survival in long term CHF
* ACE inhibitors
* AT1 receptor antagonists
Side Effects
* ACE inhibitors
+ cough
+ angioneurotic edema
+ hypotension
+ hyperkalemia
* ACE inhibitors and ATI receptor antagonists are both teratogenic

Vasodilators
* Goal: reduce TPR without causing large decrease in BP
* reduce preload
* reduce afterload
* relieves symptoms
* increase exercise tolerance

Drugs Used
* NO Donors
o Nitroglycerin
+ acute ischemia or acute heart failure
+ orally active
+ also administered I.V. for peripheral vasodilation
+ quick onset for acute relief
o Isosorbide dinitrate/hydralazine
+ chronic administration for long-term symptom relief
+ administered I.V.

Drugs Used
* Nesiritide
o recombinant brain-natriuretic peptide (BNP)
o BNP is secreted from ventricular myocytes in response to stretch
o vasodilator: increases cGMP in SMCs
+ decrease afterload/preload
o inhibits cardiac remodelling
o suppresses aldosterone secretion
o administered IV for acute decompensated CHF
o adverse effects: hypotension, renal failure (?)

Diuretics
* used in CHF to reduce extracellular fluid volume
* primarily used in patients with acute CHF with volume overload
* IV infusion causes immediate and predictable diuresis for immediate relief
* Goal: reduce preload/afterload
* overdosing can result in excessive reduction in preload, overreduction in stroke volume
* thiazide and loop diuretics (i.e. Furosemide) commonly used as adjunct therapies in CHF

Aldosterone Antagonists

* elevated AngII levels increase production of aldosterone in the adrenal cortex (~20X increase)
* aldosterone activates mineralocorticoid receptors in renal epithelial cells in kidney
* aldosterone promotes
o Na+ retention, Mg2+ and K+ loss
o increased SNS activity
o decreased PSNS activity
o myocardial/vascular fibrosis

Therapeutic Use
* Goal: inhibit aldosterone negative effects in CHF
* aldosterone receptor antagonists
o spironolactone
o eplerenone
* both antagonists reduce mortality in patients with moderate to severe CHF
* only use in patients with normal renal function and K+ levels
* use with K+ sparing diuretic

Side Effects
* hyperkalemia
* agranulocytosis
* anaphylaxis
* hepatoxicity
* renal failure
* Spironolactone: gynecomastia, sexual dysfunction
* Eplerenone: arrhythmia, myocardial infarct/ischemia

Congestive Heart Failure

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