Final scope for the systematic review of the clinical and cost effectiveness evidence for the prevention of ventilator-associated pneumonia (VAP) Contents 1. AIM...2 2. BACKGROUND...2 3. INTERVENTIONS...3 4. OUTCOMES...3 5. PICO...3 6. LITERATURE SEARCHING...3 7. INCLUSION AND EXCLUSION CRITERIA...4 7.1 Types of studies...4 8. POPULATION...4 9. ANALYSIS...4 10. SCOPING SEARCHES...4 11. COST EFFECTIVENESS...5 12. CONCLUSIONS...5 13. ACKNOWLEDGEMENTS...5 APPENDIX I DATABASES SEARCHED...I Ventilator Associated Penumonia...i APPENDIX II SEARCH STRATEGIES...II Medline search for epidemiology papers...ii Medline search for prevention papers...iii Medline search for Cost Effectiveness papers...iv
National Institute for Health and Clinical Excellence Review Body for Interventional Procedures (ReBIP) Prevention of Ventilator-Associated Pneumonia 1. Aim The aim of this systematic review is to consider the clinical and cost effectiveness evidence of a selective number of interventions for the prevention of ventilatorassociated pneumonia (VAP). For the purpose of this review clinical effectiveness will be defined as interventions applicable in a UK setting. 2. Background Ventilator-associated pneumonia (VAP) is defined as nosocomial pneumonia in a patient on mechanical ventilatory support (by endotracheal tube or tracheostomy) for 48 hours. VAP is most accurately diagnosed by quantitative culture and microscopy examination of lower respiratory tract secretions.1 However, for the diagnosis of VAP, usually three or more of the following are required: fever, leukocytosis, purulent secretions, and an infiltrate on chest radiography. VAP is a medical condition that results from infection which floods the small, air-filled sacs (alveoli) in the lung responsible for absorbing oxygen from the atmosphere. VAP is distinguished from other kinds of infectious pneumonia because of the different types of microorganisms responsible, antibiotics used to treat, methods of diagnosis, ultimate prognosis, and effective preventive measures. Extent of the problem VAP is a primary problem in intensive care units, and causes complications in 8-28% of patients receiving mechanical ventilation.2 For critically ill and postoperative patients receiving mechanical ventilation, VAP is a significant cause of morbidity and mortality.3,4% Nature of the problem A study investigating the incidence and risk factors of VAP in 16 intensive care units reported an incidence rate of 17.5%5 A one-year prospective cohort survey, set in an eight-bed medical intensive care unit reported that 38% of mechanically ventilated patients developed VAP.6 Treatment of VAP is ideally matched to known causative bacteria. However, when VAP is first suspected, the bacteria causing infection is typically not known and broad-spectrum antibiotics are given (empiric therapy) until the particular bacterium and its sensitivities are determined. Empiric antibiotics should take into account both the risk factors a particular individual has for resistant bacteria as well as the local prevalence of resistant microorganisms. If a person has previously had episodes of pneumonia, information may be available about prior causative bacteria. The choice of initial therapy is therefore entirely dependent on local knowledge and will vary from hospital to hospital. Successful treatment of patients with VAP is a difficult and complex undertaking. Even with the broad clinical experience of this disease, no consensus has been reached concerning issues as basic as the optimal antimicrobial regimen or its duration.2 2
3. Interventions The interventions identified for consideration by this review are Prophylactic antibiotics, Body position, Kinetic bed therapy and care bundles (combinations of various interventions) that are used to reduce the risk of contracting VAP. An example of a care bundle is the IHI (Institute for Healthcare Improvement) ventilator bundle which includes four key components, Elevation of the head of the bed, Sedation Hold, Peptic ulcer disease (PUD) prophylaxis and Deep venous thrombosis (DVT) prophylaxis (unless contraindicated). The research team will looked at the individual aspects of identified care bundles, where evidence is available. 4. Outcomes The primary outcome to be considered will be incidence and reduced risk of VAP, secondary outcomes will be mortality, average duration of mechanical ventilation and average length of stay in intensive care. 5. PICO A PICO table is displayed below as a summary of the proposed review. Population Mixed group of adult (>16 years) ICU patients, at risk of ventilator associated pneumonia (occurring 48 hours after endotracheal intubation and initiation of mechanical ventilation). Intervention(s) Prophylactic antibiotics Body position Kinetic bed therapy Care bundles Current standard treatments (comparators) The current standard treatment for VAP, broadspectrum antibiotics or Empiric antibiotics. Outcomes Relevant outcome measures include: incidence and reduced risk of VAP as a primary outcome and mortality, average duration of mechanical ventilation and average length of stay in intensive care as secondary outcomes. 6. Literature Searching Extensive electronic searches will be conducted to identify reports of published, unpublished and ongoing studies. We will include conference abstracts and other grey literature sources, such as IHI initiatives in the UK and worldwide. The search strategies will be designed to be sensitive and will include appropriate subject 3
headings and text word terms. The search strategy and results are presented as an appendix. In addition we will hand search reference lists of included studies for additional papers and seek expert opinion. 7. Inclusion and exclusion criteria 7.1 Types of studies We will include systematic reviews and Randomised Controlled Trials (RCTs) to assess the effectiveness of different types interventions used in the prevention of VAP. Where the same data are reported in multiple publications, we will include only the most recent unless there are any new or additional data. We will not reject a study only on the grounds of sample size but we will restrict the language to English only due to the short time scale of this review. Case studies will be excluded from the review. 8. Population The population of interest will be adult patients receiving mechanical ventilation in intensive care. Accurate data on the epidemiology of VAP are limited by the lack of standardised criteria for its diagnosis, therefore the author s definition of VAP will be used. 9. Analysis The quality of the studies will be assessed using standard quality assessment checklist. One assessor will abstract the data using the agreed data abstraction forms and tabulate the data. A sample will be checked by a second assessor. Summary tables will be presented for study results. Where sufficient data are available, meta-analysis will be carried out Where it is not possible to carry out a meta-analysis, other statistical techniques will be applied where possible calculating confidence intervals. Where this is not possible qualitative analysis of the data will be presented. The review will seek to identify the extent of VAP and identify possible solutions that are could be implemented in the UK intensive care setting. 10. Scoping Searches The scoping searches have identified the following papers, which may be potentially relevant: Six studies that discuss the incidence of VAP. Three studies that discuss outcomes 4
Fourteen studies that discuss risk. One comparative study This study was carried out to determine if an educational initiative could decrease rates of ventilator-associated pneumonia in a regional health-care system. It appears to be a before-after study. Thirteen reviews of VAP or patient safety practices. Four cohort studies One experimental design/descriptive study that aimed to evaluate the nurses' knowledge and to highlight the causes that hinder evidence-based guidelines for preventing ventilator-associated pneumonia implementation. Five randomised studies, in these studies the only randomised process used was the randomisation of patients, no inclusion/exclusion criteria was mentioned in the abstract. Two RCTs on the prevention of VAP. 11. Cost Effectiveness The evidence from the literature review will inform estimates of the relative effectiveness of the identified interventions in preventing cases of VAP, which will form the basis for the cost-effectiveness analysis. Cost estimates for the interventions will be based on the resource use associated with the reported application of the interventions and discussions with clinical experts, to which unit costs will be attached. Cost and QALY impacts of VAP will be sought from a separate literature review of the consequences of VAP, including cost-effectiveness studies of alternative methods of treating VAP, utility studies. If insufficient data are identified, it will be necessary to develop patient pathways describing the course of the disease to which estimated costs and utility weights can be attached in order to estimate aggregate costs and QALYs. 12. Conclusions We consider that due to the short time scale of this review, only systematic reviews and RCTs in the English language will be included in the main review. Only the stated interventions for the prevention of VAP in adult patients will be covered in this review. However, we will consider other studies as appropriate for the cost effectiveness analysis. 13. Acknowledgements We thank Dr. Duncan Young (Adult Intensive Care Unit, John Radcliffe Hospital, Oxford) for providing specialist advice. References 5
(1) Mayhall CG, Mayhall CG. Ventilator-associated pneumonia or not? Contemporary diagnosis. [Review] [35 refs]. Emerging Infectious Diseases 2001 Mar;7(2):200-4. (2) Chastre J, Fagon JY, Chastre J, Fagon JY. Ventilator-associated pneumonia. [Review] [429 refs]. American Journal of Respiratory & Critical Care Medicine 2002 Apr 1;165(7):867-903. (3) Heyland DK, Cook DJ, Griffith L, Keenan SP, Brun-Buisson C. The Attributable Morbidity and Mortality of Ventilator-Associated Pneumonia in the Critically Ill Patient. American Journal of Respiratory & Critical Care Medicine 1999;159:1249-56. (4) Fagon JY, Chastre J, Hance AJ, Montravers P, Novara A, Gilbert G. Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay. American Journal of Medicine 1993;94:281. (5) Cook DJ, Walter SD, Cook RJ, Griffith LE, Guyatt GH, Leasa D, et al. Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients.[see comment]. ANN INTERN MED 1998 Sep 15;129(6):433-40. (6) Elatrous S, Boujdaria R, Merghli S, Ouanes L, Boussarsar M, Nouira S, et al. Incidence and risk factors of ventilator-associated pneumonia: A one-year prospective survey. Clinical Intensive Care 1996;7(6):276-81. 6
Appendix I Databases searched Ventilator Associated Penumonia Database Host/system Date searched No. of hits Location of search strategy Scoping search CENTRAL Cochrane Library 17/04/07 135 Cochrane Reviews Cochrane Library 17/04/07 3 CINAHL Ovid 17/04/07 Cost 81 Epidemiology - 146 Prevention - 231 Citation Indexes WOK 17/04/07 Cost 115 Epidemiology - 94 Prevention - 643 CRD Databases 17/04/07 45 Embase Ovid 17/04/07 Prevention 673 1980 - Cost 233 MEDLINE 1950- Epidemiology - 397 Ovid 17/04/07 Prevention 572 Cost 167 Epidemiology - 348 NHS EED Cochrane Library 17/04/07 25 NHS HTA Cochrane Library 17/04/07 0 Other Reviews Cochrane Library 17/04/07 4 MEDLINE in Process Ovid 17/04/07 Epidemiology 23 Prevention 39 Cost - 10 Notes i
Appendix II Search Strategies Medline search for epidemiology papers Database: Ovid MEDLINE(R) <1950 to April Week 1 2007> Search Strategy: -------------------------------------------------------------------------------- 1 Pneumonia, Ventilator-Associated/ (62) 2 ventilator-associated pneumonia.tw. (1095) 3 1 or 2 (1114) 4 Pneumonia/ (27958) 5 Cross Infection/ (32126) 6 4 and 5 (1462) 7 Ventilators, Mechanical/ (6830) 8 6 and 7 (100) 9 3 or 8 (1163) 10 natural history.mp. or exp Natural History/ (23324) 11 incidence.mp. or exp Incidence/ (365697) 12 prevalence.mp. or exp Prevalence/ (224346) 13 exp Epidemiology/ or epidemiology.mp. (82136) 14 or/10-13 (637484) 15 9 and 14 (344) 16 from 15 keep 1-344 (344) 17 Pneumonia, Ventilator-Associated/ (62) 18 ventilator-associated pneumonia.tw. (1095) 19 ventilator-acquired pneumonia.tw. (20) 20 17 or 18 or 19 (1130) 21 Pneumonia/ (27958) 22 Cross Infection/ (32126) 23 21 and 22 (1462) 24 Ventilators, Mechanical/ (6830) 25 23 and 24 (100) 26 20 or 25 (1179) 27 natural history.mp. or exp Natural History/ (23324) 28 incidence.mp. or exp Incidence/ (365697) 29 prevalence.mp. or exp Prevalence/ (224346) 30 exp Epidemiology/ or epidemiology.mp. (82136) 31 or/27-30 (637484) 32 26 and 31 (348) ii
Medline search for prevention papers Database: Ovid MEDLINE(R) <1950 to April Week 1 2007> Search Strategy: -------------------------------------------------------------------------------- 1 Pneumonia, Ventilator-Associated/ (62) 2 ventilator-associated pneumonia.tw. (1095) 3 ventilator-acquired pneumonia.tw. (20) 4 1 or 2 or 3 (1130) 5 Pneumonia/ (27958) 6 Cross Infection/ (32126) 7 5 and 6 (1462) 8 Ventilators, Mechanical/ (6830) 9 7 and 8 (100) 10 4 or 9 (1179) 11 Primary Prevention/ (8967) 12 prevent$.tw. (548823) 13 antibiotic$.tw. (148227) 14 antiseptic.tw. (2264) 15 iodine.tw. (23483) 16 oral decontaminat$.tw. (21) 17 or/11-16 (712280) 18 10 and 17 (572) iii
Medline search for Cost Effectiveness papers Database: Ovid MEDLINE(R) <1950 to April Week 1 2007> Search Strategy: -------------------------------------------------------------------------------- 1 Pneumonia, Ventilator-Associated/ (62) 2 ventilator-associated pneumonia.tw. (1095) 3 ventilator-acquired pneumonia.tw. (20) 4 1 or 2 or 3 (1130) 5 Pneumonia/ (27958) 6 Cross Infection/ (32126) 7 5 and 6 (1462) 8 Ventilators, Mechanical/ (6830) 9 7 and 8 (100) 10 4 or 9 (1179) 11 Economics/ (24856) 12 exp "Costs and Cost Analysis"/ (128397) 13 economic value of life/ (4836) 14 exp economics hospital/ (14634) 15 exp economics medical/ (11321) 16 economics nursing/ (3736) 17 exp models economic/ (5131) 18 Economics, Pharmaceutical/ (1755) 19 exp "Fees and Charges"/ (22848) 20 exp budgets/ (9923) 21 ec.fs. (224975) 22 (cost or costs or costed or costly or costing$).tw. (171688) 23 (economic$ or pharmacoeconomic$ or price$ or pricing$).tw. (86888) 24 quality adjusted life years/ (2860) 25 (qaly or qaly$).af. (1621) 26 or/11-25 (445706) 27 10 and 26 (167) iv