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7/30/2019 inhalational therapy in ICU
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INHALATIONAL ANTIBIOTICSIN ICU
7/30/2019 inhalational therapy in ICU
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WHY NEW ROUTE
COLONIZATIONOROPHARHYNGEAL
TRACHEOBRONCHEAL
Tracheobronchitis
Pneumonea
PROPHYLAXIS
TREATMENT
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n Higher therapeutic dose– dose delivery to target organ
higher Vd in critically ill patient
n Higher dose delivery to distal airways and lung parenchyma- lower therapeuticdose
n Lower risk of systemic side effects
WHY NEW ROUTE
Inhaled therapy
Systemic Antibiotics
INHALATIONAL ANTIBIOTICS IN ICU
ADVERSEEFFECTS
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Lung distribution and pharmacokinetics of Lung distribution and pharmacokinetics of nebulizednebulized tobramycintobramycin--Le Conte P, Am revLe Conte P, Am rev respresp dis1993, 147:1279dis1993, 147:1279--8282
IS IT EFFECTIVE
Concentration of Concentration of gentamycingentamycin in bronchial secretion after intramuscular andin bronchial secretion after intramuscular and endobronchialendobronchial
administrationadministration-- KlasterskyKlastersky J, JJ, J clinclin pharmacolpharmacol, 1975, 15, 518, 1975, 15, 518--2424
GentamycinGentamycin 2mg/kg: concentration achieved2mg/kg: concentration achieved-- endobronchialendobronchial secretion serumsecretion serum
I.M. routeI.M. route <2ug/ml >6ug/ml<2ug/ml >6ug/ml
EndobronchialEndobronchial routeroute >400ug/ml <1ug/ml>400ug/ml <1ug/mlTo prevent toxicity DESIRED TROUGH SERUM CONCTo prevent toxicity DESIRED TROUGH SERUM CONC-- < 1< 1--22 ugug /ml /ml
(( GoodmannGoodmann and Gilmanand Gilman’’s the pharmacological basis of therapeutics 11s the pharmacological basis of therapeutics 11thth ediedi--2006)2006)
Mean lung tissue conc. 5.5ug/ml after 4 hours ;Mean lung tissue conc. 5.5ug/ml after 4 hours ; 33--61ug/ml after 12 hours61ug/ml after 12 hours
InhaledInhaled amikacinamikacin achieves high epithelial lining fluid concentration in Gramachieves high epithelial lining fluid concentration in Gram negneg pneumoneapneumonea
inin intubatedintubated an mechanically ventilated patients.an mechanically ventilated patients.LuytLuyt CE, Jacob A, Am JCE, Jacob A, Am J RespirRespir CritCrit Care Med 2007; 175:A 328Care Med 2007; 175:A 328
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IS IT EFFECTIVE
dose delivered to lung was 21.9% of neb charge
sputum conc- peak- 1005-5839 ug/ml, trough- 234-520 ug/ml
serum conc- undetectable in all (except one who was in renal failure-8.7 ug/ml of amikacin)
DESIRED TROUGH CONC OF AMIKANCIN- < 5-10 ug/ ml
weekly culture revealed eradication of pseudomonas, serratia mersescence, enterobactor
aerogenes
EFFICACY IN CRITICALLY ILL PATIENT TO BE DETERMINED
Aerosolized antibiotic in mechanically ventilated patients: deliAerosolized antibiotic in mechanically ventilated patients: delivery and response.very and response.
Lucy B. Palmer, Gerald C.Lucy B. Palmer, Gerald C. SmaldoneSmaldone,, critcrit care med; 1998; 26:1:31care med; 1998; 26:1:31--3939
AerosolizedAerosolized amikacinamikacin andand gentamycingentamycin for 14for 14--21 days in 9 cycles in mechanically21 days in 9 cycles in mechanically venilatedvenilated
stable patients colonized with Gstable patients colonized with G negneg organism producing purulentorganism producing purulent secrectionsecrection
INHALATIONAL ANTIBIOTICS IN ICU
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PAST
n Documented efficacy in cystic fibrosis
n
Data are scarce in critically ill patients on mechanicalventilation
since 1950 - earlier trial ended in increased incidence of infection and adverse
effects
( Aerosol Polymyxin and Pneumonia in Seriously Ill Patients T. W. Feeley, G. C. du Moulin,,
N Engl J Med 1975; 293:471-475)
INHALATIONAL ANTIBIOTICS IN ICU
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Falagas ME, Siempos II, Bliziotis IA, Michalopoulos: Administration of
antibiotics via the respiratory tract for the prevention of ICU-acquired pneumonia:
a meta-analysis of comparative trials. Crit Care 2006; 10:R123.
1950 – 2005:Meta-analysis of 5 RCTs (414 pts)ICU-acquired pneumonia was statistically less common in the cohorts
receiving aerosolized antibiotic prophylaxis.
No difference in mortality
Could not evaluate effect on resistance of bacteria
PREVENTION OF COLONIZATION AND
NOSOCOMIAL PNEUMONEA
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PREVENTION OF NOSOCOMIAL PNEUMONEA
Characteristics of comperative trial included in meta analysis
Polymyxin B 2.5 mg/kg bw/d in 6 divided doses1973 58Greenfield et al
Gentamycin 80 mg q8h1974 85Klatersky et al
Polymyxin B 2.5 mg/kg bw/d in 6 divided doses1975 692Klick et al
Gentamycin 40 mg q6h1981 40Vogel et al
Gentamycin 40 mg q6h1992 162Lode et al
Tobramycin 80 mg q6h1993 69Rathgerber et al
Colistin 0.2 mu q3h1994 598Rouby et al
Ceftazidime 250 mg q12h2002 40Wood et al
Study drug/ doseYear Pt. no.Reference
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INHALATIONAL ANTIBIOTICS IN ICU
TREATMENT OF TRACHEOBRONCHITIS
Palmer LB, Smaldone GC, Chen JJ, et al.
Aerosolized antibiotics and ventilator-associated tracheobronchitis in the ICUCrit Care Med 2008; 36:2008–2013.
reduced clinical signs of respiratory infection,
pulmonary infection score, progression to VAP,
Reduced bacterial resistance,
reduced use of systemic antibiotics,
and earlier discontinuation of mechanical ventilation.
Based on Gram stain of the
tracheal aspirate, 43 patients
received aerosolized
vancomycin or gentamycin
for 14 days versus placebo.
Iv antibiotics prescribed on
physician discretion
No difference in WBC before or after therapy
No difference in mortality
INHALATIONAL ANTIBIOTICS IN ICU
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INHALATIONAL ANTIBIOTICS IN ICU
TREATMENT OF TRACHEOBRONCHITIS
Nseir S, Favory R, et. Antimicrobial treatment for ventilator associated tracheobronchitis
A randomised controll multicentre study. Crit Care 2008;12:R62
Significant decrease in progression to VAP
Earlier discontinuation of mechanical ventilation
Reduced mortality
Serial ETA monitoring to diagnose VAP
Randomised to receive aerosolized therapy vs no therapy
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Ioannidou E, Siempos II, Falagas ME. Administration of antibiotics via the
respiratory tract for the treatment of patients with nosocomial pneumonia: a
meta-analysis. J Antimicrob Chemother 2007; 60:1216–1226.
INHALATIONAL ANTIBIOTICS IN ICU
TREATMENT OF NOSOCOMIAL PNEUMONEA
No difference was demonstrated for mortality,
emergence of resistance, or adverse event.
META ANYLYSIS OF 5 TRIALSStatistically higher success rate for the
treatment of nosocomial pneumonia
if receiving inhaled or endotracheally instilled antibiotics
in the 176 patients.
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Falgas ME, Agrafiotis M, Athanassa Z, et al
Administration of antibiotic through respiratory tract as monotherapy for pneumoneaExper Rev Antiinf Ther 2008;6:447-452
INHALATIONAL ANTIBIOTICS IN ICU
MONOTHERAPY OF NOSOCOMIAL PNEUMONEA
TREATING PATIENT WITH VAP WITH AEROSOLIZED ANTIBIOTIC ALONE IS
PREMATURE
This therapy might be considered when systemic access is not available,
refused by the patient or concern regarding bioavailability to lung or
systemic toxicity
INHALATIONAL ANTIBIOTICS IN ICU
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Role of inhaled anibacterial in hospital aquired and ventilator associated
pneumonea .
Lesho E. Expert Rev Anti Infect Ther 2005;3(3):445-451
INHALATIONAL ANTIBIOTICS IN ICU
RECOMMENDATION FOR PREVENTION OF NOSOCOMIAL
PNEUMONEA
Aerosolized antibiotics: a critical appraisal of
their use.
Hagerman JK, Hancock KE, Klepser ME. Expert Opin Drug Deliv 2006;3(1)71-78
There are limited data available to support the routine use of this modality
Despite optimized delivery systems…inhaled antibiotics can still not be recommended for
preventing VAP
Recent evidence base reviews have interpreted supporting data as week
Universally recommended against routinely using for VAP prophylaxix untill stronger data
are available
INHALATIONAL ANTIBIOTICS IN ICU
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NO RECOMMENDATION
ABOUT ANTIBIOTIC
INDICATION ,SELECTION, DOSE,
FREQUENCY, DURATION
RECOMMENDATION FOR TREATMENT OF NOSOCOMIAL
PNEUMONEA
MULTIPLE CONSENSUS GROUP RECOMMEND AGAINST USING IN
ESTABLISHED VAP ESPECIALLY AS MONOTHERAPY
( Neil R MacIntyre, Bruce K Rubin MEngr, Should Aerosolized antibiotic be administered to prevent
or treat VAP in patient who do not have cystic fibrosis? Respir Care, April 2007;52;4:416-20 )
CAN BE RECOMMENDED TO TREAT MDR VAP – COLISTIN AND AGS
(C.E. Luyt, Alain Combes, Ania Nieszkowska, JL Trouillet, Aerosolized antibiotics to treat VAP.
Curr Opin infect dis ;2009;22:154-158)
Legal concernLegal concern--
airway as a route of airway as a route of AntiobioticAntiobiotic delivery not approveddelivery not approvedby USFDAby USFDA
(EVEN FOR TOBRAMYCIN FOR WHICH SPECIFIC PREPARATION(EVEN FOR TOBRAMYCIN FOR WHICH SPECIFIC PREPARATION
TOBITOBI IS AVAILABLE)IS AVAILABLE)
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IT IS VERY POSSIBLE THAT AEROSOLIZED ANTIBIOTIC MAY BECOME
A MAINSTAY IN PREVENTING VAP IN FUTURE
Neil R MacIntyre, Bruce K Rubin MEngr, Should Aerosolized antibiotic be administered to prevent or treat
VAP in patient who do not have cysic fibrosis? Respir Care, April 2007;52;4:416-20 )
INHALATIONAL ANTIBIOTICS IN ICUINHALATIONAL ANTIBIOTICS IN ICU
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INHALATIONAL ANTIBIOTICS IN ICU
PROBLEMS
BRONCHOSPSMPretreatment with albuterol 2.5 mg
SYSTEMIC TOXICITY AND INTRODUCTION OF NEW INFECTION
PATIENT RELATED DEVICE RELATED DRUG RELATED
DRUG DELIVERY
VENTILATOR RELATED CIRCUIT RELATED
EMERGENCE OF
RESISTANCE
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INHALATIONAL ANTIBIOTICS IN ICU
PROBLEMS- DRUG DELIVERY
PATIENT RELATED:•Airway obstruction
•Dynamic hyperinflation
•PVA
VENTILATOR RELATED:•MODE- spontaneous, volume control
•Vt- higher >500, small Vd•RR- lower
•Ti- longer
•flow waveform- square waveform better
than descending ramp
• triggering- flow triggering –loss of drug
DEVICE RELATED:
• Type of nebulizer- Jet/ ultrasonic
• Flow – 6-8 lt
• Position in circuit- around 35-45 cm from
Y connector or ETT
• Continuous/ intermittent operation
• duration of nebulization
CIRCUIT RELATED:•ETT-
• Inhaled gas humidity• Inhaled gas density/ viscocity
• DRUG RELATED:• Dose
• Particle size- 1-5 micron
• Volume- 4-5 ml( neb charge)
INHALATIONAL ANTIBIOTICS IN ICU
Tubing acts asspacer deviceand increases
respirablefraction
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SPECIFIC DOSING OF DRUGS:
• Amikacin- 400 mg q8-12h
• Gentamycin- 80 mg q8h
• Tobramycin ( TOBI)- 300 mg q 12h
• colistin- 150 mg ( 2 mu) q 8-12h
• Vancomycin- 125 mg q8h
EACH DOSE SHOULD BE DILUTED TO A TOTAL VOLUME OF 4 ml
INHALATIONAL ANTIBIOTICS IN ICU
Aerosolized antibiotic therapy in ICU- guidelines prepared by Surgical Education, Orlando Regional Medical
Centre. Approved 05-05-2009
INHALATIONAL ANTIBIOTICS IN ICU