Management of Severe Pneumonia in Children · itbtdintubated pati ttients with community‐acquidired pneumonia Survival graph for severe CAP c ventilator Survival graph for sepsis/septic

ffManagement of Management of Severe Pneumonia in ChildrenSevere Pneumonia in ChildrenSevere Pneumonia in ChildrenSevere Pneumonia in Children

Sorasasak Lochindarat, M.D.Queen Sirikit National Institute of Child Health

E id i lEpidemiology

Figure1: Distribution of 10.5 million deaths among children less than 5 years old in all developing countries, (WHO)

Bull World Health Organ 2008;86:408-416.

Bull World Health Organ 2008;86:408-416.

Bull World Health Organ 2008;86:408-416.

Etiologygy

Figure : Etiology of severe pneumonia in children in developing countries

J Clin Invest 2008;118(4):1291-300.

Figure : Etiology of severe pneumonia in children in developing countries

Progressive Primary Pulmonary Tuberculosis : ARDS

Aetiology of pneumonia in children with severe malnutrition

(Trop Med Int Health 2009;14:1173‐1189.)

VIRUSES ASSOCIATED WITH PNEUMONIAIN CHILDREN IN CHILDREN

Age Group

Viruses Infants Preschool School Age

Respiratory syncytial +++ ++ +

Parainfluenza type 1,3 ++ + +

I fl AInfluenza A + ++ ++

Influenza B + + ++

Parainfluenza type 2 + + +

Adenovirus + + +

Measles +* +* +

Cytomegalovirus + + +Cytomegalovirus + + +

Metapneumovirus + + +

*Important cause in developing countries.

Aetiology and epidemiologyAetiology and epidemiology

• Strep pneumoniae is the most common bacterialStrep pneumoniae is the most common bacterial 

cause of pneumoniae in children, followed by 

mycoplasma and chlamydophila pneumoniae

• Viruses are most commonly found in younger

f d f• 8‐40 % of CAP is mixed infection

• 20 60 % of CAP a pathogen is not identified• 20‐60 % of CAP, a pathogen is not identified

• 14‐35 % of CAP is caused by virus in childreny

Severity Assessment

(Pediatr Respir Rew 2011;12:52‐59.)

>

WHO/ARI/91.20

(Thorax 2002;57 suppl 1 : i1‐24.)

Indication for transfer to intensive careIndication for transfer to intensive care

• Failing to maintain SaO2 > 92 % in FiO2 > 0.6

• Shock

• Rising RR and PR with severe respiratory 

distress and exhaustion, + raised PaCO2

R l i l b hi• Recurrent apnea or slow irregular breathing 

(Thorax 2002;57 suppl 1 : i1‐24.)

I i iInvestigation

Defining Bacterial PneumoniaDefining Bacterial PneumoniaSensSens

Clinical diagnosisClinical diagnosis

Any XAny X rayray

SensSens

Any XAny X--rayrayabnormalityabnormality

Lobar consolidationLobar consolidation

C ltC ltCulture provenCulture provenbacterial pneumoniabacterial pneumonia

SpecSpec

Chest radiographyChest radiography

• CXR (PA, lateral) in all hospitalized patients 

with CAP

• Repeat CXR in children that not improve or 

deteriorate after 48 72 hrs of ATBdeteriorate after 48‐72 hrs. of ATB

(Clinical Infectious Diseases, Aug 2011)

Blood cultureBlood culture

• Should be obtained in presumed bacterial CAP 

that is moderate to severe

• Repeated blood cultures in bacteremic CAP

LabLab

• Rapid test for flu and RSV• Rapid test for flu and RSV

• Acute phase reactants (ESR CRP serum• Acute‐phase reactants, (ESR, CRP, serum 

procalcitonin), can not distinguish between p ), g

viral and bacterial CAP

• Pulse oximetry should be performed in all 

severe CAP

Atypical pathogens

• Serologic test for IgM of chlamydiphila pneomonia 

andMycoplasma pneumonia

• Quadrupling of serum IgG between acute and 

convalescent phase but limited clinical valueconvalescent phase, but limited clinical value

• Cold agglutinin for M. pneumoniae is low specificity gg p p y

and positive predictive value

• PCR for C. pneumoniae and M. pneumoniae is helpful 

f id di ifor rapid diagnosis(Curr Opin Pulm Med 2005;11:218‐225.)

Additional tests for severe/ Life‐threatening CAPAdditional tests for severe/ Life‐threatening CAP

• Tracheal aspirations/Bronchoscopic or blind bronchoalveolar larvage forg

• Gram stain, culture

• Rapid test for flu and RSVp

• PCR for virus (flu, parainflu, RSV, adeno, rhino, humanMPV)

• AFB, PCR for TB, culture for TBAFB, PCR for TB, culture for TB

• Modified AFB (Nocardia)

• Fresh smear for fungus, culture for fungusFresh smear for fungus, culture for fungus

• Galacfomannan (Aspergillus)

Use of bacterial urine‐antigen detection in the diagnosis of pediatric LRTI

Urine antigen was present in

• 4 % of asymptomatic children

• 16 % of children with AOM16 % of children with AOM

• 24 % of children with CAP

The specificity is too poor for diagnosis of CAP

(P di t i 1996 78 1 9 )(Pediatrics 1996;78:1‐9.)

TreatmentTreatment

E i i Th f S CAP i P di t iEmpiric Therapy for Severe CAP in Pediatrics

To cover bacterial CAP To cover atypical CAP To cover flu CAP

f / f l h O lt i iCeftriaxone/cefotaxime plus vancomycin/clindamycin for suspected MRSA 

Azithromycin OseltamivirZanamivir

alternative for cephalosporins: Levofloxacin

alternative • Other macrolide• Levofloxacin

Anti‐infective treatment of severe CAPAnti‐infective treatment of severe CAP

• Ceftriaxone or cefotaxime for

N t f ll i i d hild• Not fully immunized children

• In region of high‐level pen resistance of invasive 

pneumococcus

• Left threatening

• empyemapy

Anti‐infective treatment of severe CAPAnti‐infective treatment of severe CAP

V i ff i h hi d• Vancomycin not more effective than third‐gen 

cephalosporins in pneumococcal pneumoniacephalosporins in pneumococcal pneumonia

• Empiric combination with a macrolide, in addition to 

a β‐lactam ATB for whom atypical pathogens can’t be 

rule out

• Vancom cin/clindam cin in addition to β lactam ATB• Vancomycin/clindamycin in addition to β‐lactam ATB 

if consistent with MRSA

General managementGeneral management • O therapy (nasal cannulae head box face mask) forO2 therapy (nasal cannulae, head box, face mask) for SpO2 < 92 % in room air

• Agitation may be a symptom of hypoxia• Agitation may be a symptom of hypoxia

• NG tube may compromise breathing

• IV fluid should be given at 80% maintenance and serum electrolytes monitored for SIADH

• Chest PT no benefit, should not be performed in children with pneumoniap

• In ill child, minimal handling may reduce metabolic and O2 requirementand O2 requirement 

Parapneumonic Effusion

Management of parapneumonic effusionsManagement of parapneumonic effusions

Size of effusion Bacteriology Chest tube drainage

Small : < 10 mm. of lat d bit ifi d

Bacterial culture and Gram stain : neg/unknown

• No thoracentesis or chest tubedecubitus or opacified

< ¼  of hemithoraxstain : neg/unknown chest tube

M d 10 i f B t i lt G Th t iMod : > 10 mm. rim of fluid but opacified < ½ hemithorax

Bacteria culture or Gram stain : neg or pos (empyema)

• Thoracentesis• Chest drain in respiratory compromise or empyema

Large : opacifies > ½ hemithorax

Bacterial culture or Gram stain : pos (empyema)

• Chest drain

Lab testing for pleural fluid Lab testing for pleural fluid 

Gram stain & bacterial culture

A i PCRAg testing or PCR

Wbc with cell differential analysis, to differentiateWbc with cell differential analysis, to differentiate 

bacterial from TB, Malignancy

Pleural fluid parameters : pH, glucose, protein, LDH 

rarely change patient management & not recommendedrarely change patient management & not recommended 

A 2 YO.girl with

pneumonia and pleural

effusion. Hemo C/S:

S.pneumoniae serotype

14 sensitive to penicillin14, sensitive to penicillin

and cefotaxime, but

clinical not improved after

ATBATB.

Chest CT scan: Loculated pleural effusion

Necrotizing Pneumonia

Necrotizing pneumonia and pneumatocelesNecrotizing pneumonia and pneumatoceles

• As a result of localized bronchiolar and alveolar necrosis

• The main cause is S. aureus, followed by 

S. pneumoniae, H. influenzae, klebsiella pneumoniaeS. pneumoniae, H. influenzae, klebsiella pneumoniae and E. coli   

• IV antibiotic until clinical improvement followed by• IV antibiotic until clinical improvement, followed by oral antibiotic for a total course of at least 3 weeks

• Most pneumotoceles disappear within 2 mo• Most pneumotoceles disappear within 2 mo, although this may take as long as 6 mo.

(Thorax 2011;66:815‐822.)

Management of pulmonary abscess or Management of pulmonary abscess or necrotizing pneumonia necrotizing pneumonia 

• can be treated with intravenous ATB

• most abscess will drain through the bronchial 

tree & healtree & heal

• well‐defined peripheral abscess without connection to bronchial tree may be drained under imagingto bronchial tree may be drained under imaging guided procedures

• aspiration• aspiration

• Drainage catheter in place

Staph Septicemia : Staph Septicemia :

septic emboli, necrotizing pneumonia, pneumothoraxp

Necrotizing pneumonia caused byMycoplasma pneumoniae in pediatricsMycoplasma pneumoniae in pediatrics

14‐year‐old girl : CXR showed consolidation RML with mod pleural effusion

Pleural fluid : wbc 690 /mm3 (N 14%, L 86%), rbc 840,000 /mm3, protein 3.8 g/dl, 

LDH 2,320 IU/L)

(Pediatr Infect Dis J 2004;23:564‐7.)

, / )

Complement fixation Ab titer =1/320

Necrotizing pneumonia caused by Mycoplasma pneumoniae in pediatricsMycoplasma pneumoniae in pediatrics

4‐year‐old boy: CXR showed total consolidation RL with pleural effusion

Pleural fluid : wbc 990 /mm3 (N 80%, L 20%), rbc 720 /mm3, protein 4.1 g/dl, LDH 3,216 IU/L)

(Pediatr Infect Dis J 2004;23:564‐7.)

Complement fixation Ab titer =1/1280

Macrolide for Very Severe PneumoniaPneumonia

Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bateremia

Prospective, multicenter, international observational study of 844 patients C bacteremic pneumococcal pneumonia

Not critically illNot critically ill

Critically illCritically illCritically illCritically ill

(Am J Respir Crit Care Med 2004;170:440-4.)

Combination antibiotic therapy with macrolides improves survival in i t b t d ti t ith it i d iintubated patients with community‐acquired pneumonia

– Prospective, observational cohort, multicenter study in 27 ICU of 9 European countries

(Intensive Care Med 2010;36:612-20.)

Combination antibiotic therapy with macrolides improves survival in i t b t d ti t ith it i d iintubated patients with community‐acquired pneumonia

Survival graph for severe CAP c ventilator Survival graph for sepsis/septic shock

(Intensive Care Med 2010;36:612-20.)

Macrolide andMacrolide andAnti-inflammatory Effect

• Macrolides and anti-inflammatory effect have been studied over the past several yearsp y

• In general, short-term (7.28 days) administration of macrolides resulted in an enhance immune response macrolides resulted in an enhance immune response, whereas long-term treatment was associated with a d d decreased response

• Most immunomodulatory effect are shared by the 14-and 15-member ring macrolides, but not 16 member ring g

Labro MT. J Antimicrob Chemother 1998;41(suppl B):37-46

Acute Respiratory Failure (ARF) /p y ( ) /

Acute Respiratory Distress SyndromeAcute Respiratory Distress Syndrome

( )(ARDS)

Respiratory Failure

• ระบบหายใจไมสามารถแลกเปลี่ยน gas ใหมีระบบหายใจไมสามารถแลกเปลยน gas ใหม

O2เพียงพอกับความตองการของรางกายO2 ง ง ง ง

และ/หรือ

• ไมสามารถกําจัด CO2 ออกจากรางกาย2

Clinical ClassificationClinical Classification

Type I failure : nonventilatory or normocapnicType I failure : nonventilatory or normocapnic respiratory failurel P O l t l P CO: low PaO2, normal to low PaCO2

Type II failure : ventilatory or hypercapnia failure:  high PaCO2 , variable PaO2

ARF criteria‐ PaO2 <  50  mm Hg2 g‐ PaCO2 >  50  mm Hg‐ absence of intracardiac shuntabsence of intracardiac shunt

Alveolar‐arterial O2 tension difference

P(A a)O = [(PB PH O) FiO PaCO /0 8] PaOP(A‐a)O2 =   [(PB ‐ PH2O) FiO2 – PaCO2/0.8] ‐ PaO2

Normal      < 30     mmHg  in  R/A

< 50     mmHg  in  FiO2 1.0

Severe RF > 450 mmHgSevere RF   > 450   mmHg

l l i l i diffAlveolar‐arterial O2 tension difference

1. ถามี hypoxemia แต P(A-a)O2 ปกติ

: alv. Hypoventilation

2 ถา P(A a)O สง : V/Q mismatch diffusion defect 2. ถา P(A-a)O2 สูง : V/Q mismatch, diffusion defect, intrapulm shunt

แกไขไดโดยให FiO2 1.0 จะทําให PaO2 สูงขึ้น ;

ยกเวน shunt

Viral Pneumonia : interstitial perihilar infiltration,hyperaeration

Human flu A(H3N2) : ARDS

Adenoviral Pneumonia : intranuclear inclusion bodybody

Invasive Pulmonary AspergillosisInvasive Pulmonary Aspergillosis

Signs of respiratory failureSigns of respiratory failure

1 Signs of resp distress1. Signs of resp. distress‐ tachypneanasal flaring‐ nasal flaring

‐ chest indrawingaccessory muscles‐ accessory muscles

‐ orthopneaadventitious sounds‐ adventitious sounds

2. Signs of tissue hypoxiacerebral hypoxia : confusion coma‐ cerebral hypoxia : confusion, coma

‐ cyanosis

Signs of respiratory failure

3. Signs of sympathetic compensationl h diearly ‐ tachycardia

‐ hypertension‐ sweating

late ‐ bradycardia‐ hypotension‐ pulsus paradoxusp p

4. Signs of respiratory muscle fatigue‐ paradoxical chest & abdominal motionparadoxical chest & abdominal motion‐ bradypneairregular breathing‐ irregular breathing

‐ apnea

Management of ARFManagement of ARF

i i & l i i1. Recognition & early interventions

‐ Respiratory distress

‐ Impending RF

‐ O2 therapy for Type I failure

‐ Mechanical ventilator for  Type II failureyp

‐ Nonconventional methods of ventilatory support

‐ Nonventilatory methods of respiratory support

Methods of O therapMethods of O2 therapy

FiO2 O2 Flow Rate

(L/min)(L/min)

Nasal cannula 0.22-0.4 0.25-4

Simple mask 0.4-0.5 6-10

Partial rebreathing mask 0.6-0.9 6-10

Non-rebreathing mask 0.95 10-15g

Head box 0.95 >10

The Harriet Lane Handbook: sixth edition

Nasal cannula Head boxNasal cannula Head box

A B

(A) P i l b hi k (B) N b hi(A) Partial rebreathing mask (B) Non-rebreathingmask

(From Kacmarek)

N b thi kNon-rebreathing mask

Management of ARF (con’t)Management of ARF (con’t)

2. Treat underlying causes

P i ti i bi l‐ Pneumonia :  antimicrobial

‐ Cardiogenic pulm edema : diuretic, inotropicCardiogenic pulm edema :  diuretic, inotropic

‐ Drug intox :  antidote

‐Massive effusion :  thoracocentesis, ICD

‐ Pneumothroax :  ICD

Management of ARF (con’t)Management of ARF (con’t)

3. Supportive care 

‐ Fluid & electrolyte Rx

CHO‐ ลด CHO

Sedative / analgesic‐ Sedative / analgesic

‐ Inotropic drugsp g

Acute Respiratory Distress SyndromeAcute Respiratory Distress Syndrome

( )(ARDS)

The American - European Consensus Conference on ARDS

ARDS characteristics :

1. Acute onset of respiratory symptoms2 Frontal chest radiograph with bilateral infiltrates2. Frontal chest radiograph with bilateral infiltrates3. No clinical evidence of left atrial hypertension (PAWP <

18 mmHg)4. PaO2/FiO2 < 200 mmHg (regardless of the PEEP level)2 2 g ( g )

(Am J Respir Crit Care Med 1994;149:818)(Am J Respir Crit Care Med 1994;149:818)

ARDS / Acute hypoxemic respiratory failureABG: PH 7.3 PaO2 60 PaCO2 45 HCO3 25 BE +2 (FiO2=0.6)ABG: PH 7.3 PaO2 60 PaCO2 45 HCO3 25 BE +2 (FiO2 0.6)

PaO2/FiO2 = 60/0.6 = 100

(Semin Pediatr Infect Dis 2006;17:65‐71.)

Prevention for CAPPrevention for CAP

• Immunization with PCV, Hib, Measles, pertussis, flu 

vaccinesvaccines

• Parents/caretakers of infants < 6 mo., including g

pregnant adolescents, should be immunized with flu & 

pertussis vaccines to protect infants from exposure 

h k f h ld b d d• High‐risk infants should be provided immune 

prophylaxis with RSV‐specific monoclonal Ab.prophylaxis with RSV specific monoclonal Ab.

ConclusionConclusion

• Pneumonia in children is the most serious illness and

difficult to diagnose

• Associated with severe morbidity, enormous burden, y, ,

both economically and public health worldwide

• Future challenges include • Future challenges include

• implementation of effective intervention

strategies

production of simple diagnostic tools• production of simple diagnostic tools

• development of effective vaccines

Thank You Very MuchThank You Very Much