Antibiotics for preventing infection in people receiving chest drains

Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

To summarise the effects of antibiotic prophylaxis for patients receiving a chest drain after clean or clean‐contaminated surgery.

Background

Description of the condition

Thoracic surgery is a specialty concerned with the diagnosis and treatment of acquired and congenital diseases that affect the chest wall, pleural and mediastinal cavity and internal organs and structures (heart, lung, trachea, oesophagus, great vessels). A chest drain or tube or closed tube thoracostomy is a device used to drain air or fluid from the chest cavity (pleural and mediastinal) and it takes the form of a tubular drain connected to a underwater seal (chest drainage collection system).

The principles of chest drainage were first described and utilised in the 19th century for the treatment of pleural empyema by Bülau 1891; Hewett 1876 and Playfair 1875. Brunn demonstrated the importance of chest drainage for elective thoracic surgery (Brunn 1929). The chest drains themselves may vary in the type of material and size (French gauge system ‐ F ‐ is used to measure the diameter of a drain; 1 F = 0.33 mm). The most commonly used materials are polyvinyl chloride (PVC) straight and silicone elastomer (Mattioli 2008; Munnell 1997) and the most popular sizes are 28F, 32F and 36F for adults and 16F, 20F and 24F for paediatric patients (Munnell 1975).

The placement of a chest drain is sometimes the sole necessary surgical intervention for treating a patient; for example in a retrospective analysis of war wounds, 82% of patients with penetrating chest trauma were treated only by the placement of a chest drain (Hardaway 1978). After thoracic surgery the placement of a chest drain is a complementary procedure that permits the drainage of air and effusions from the thoracic cavity (pleural, pericardial or mediastinal) and is necessary after the majority of thoracic surgical procedures (Nakamura 2009; Watkins 1961).

Although it plays an essential role in thoracic surgery, the chest drain itself is a prosthetic material that connects the internal with the external environment and can therefore increase the chance of infection (Bailey 2000; Collop 1997; Eddy 1989). Surgical site infections (SSIs) are divided into incisional and organ/space infections (Horan 1992). The identification of SSIs involves the interpretation of clinical and laboratory findings, defined in Appendix 1. The SSI is one of the most common health care‐associated infections and can increase the length of hospital stay and the associated cost per patient (Plowman 1999).

Description of the intervention

Surgical wounds are classified into clean, clean‐contaminated, contaminated and dirty‐infected, depending on the anatomical location and nature of the surgery (Appendix 2; Garner 1985; Simmons 1982). Antibiotic prophylaxis (AP) is the use of antibiotics before, during or after a diagnostic, therapeutic or surgical procedure to prevent infectious complications. It is used for clean and clean‐contaminated surgical wounds (the administration of antibiotics for contaminated or dirty‐infected surgical wounds is not considered prophylaxis but rather treatment (Mangram 1999). Patients undergoing procedures that involve the implantation of prosthetic material and those for whom the consequences of infection are serious or who have high risk of SSI should receive antibiotic prophylaxis (Mangram 1999).

The principles of antibiotic prophylaxis are that the prophylactic antibiotic should be given for a short duration only; the antibiotic selected for this indication should not be used therapeutically; the antibiotic selected should not readily lead to the emergence of microbial resistance; and that the antibiotic used for surgical prophylaxis should be relatively free of side effects and relatively cheap (Allerberger 2008).

How the intervention might work

The use of antibiotic prophylaxis for patients receiving a chest drain may reduce the risk of a SSI and consequently reduce morbidity, mortality and costs related to the surgery.

Why it is important to do this review

Hospital‐acquired infections (HAI) pose a large health burden (Gordon 2006) due the potential morbidity related to the SSI (Astagneau 2001) and the implications of the misuse of antibiotics (increased possibility of generating antimicrobial resistance, risk of allergic reaction to the drug in patients and increased cost of treatment) (Kristinsson 2008). The evidence for the use of antibiotic prophylaxis for chest drain use after clean and clean‐contaminated surgery has not previously been summarised.

Objectives

To summarise the effects of antibiotic prophylaxis for patients receiving a chest drain after clean or clean‐contaminated surgery.

Methods

Criteria for considering studies for this review

Types of studies

Randomised controlled trials (RCTs).

Types of participants

People (children and adults) receiving chest drains after clean and clean‐contaminated surgical procedures.

Types of interventions

Eligible comparisons would be:

• antibiotic compared with placebo or no antibiotic;

• antibiotic 1 compared with antibiotic 2.

Types of outcome measures

Primary outcomes

• Infection (to include surgical site infection, superficial and deep incisional and organ/space ‐ mediastinal, pericardial, pleural or pulmonary infection).

• Mortality.

Secondary outcomes

• Length of hospital stay.

• Costs.

• Adverse events following interventions.

Search methods for identification of studies

Electronic searches

We will carry out the following electronic searches:

• the Cochrane Wounds Group Specialised Register (latest);

• the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (latest issue);

• Ovid MEDLINE (1950 to present);

• Ovid EMBASE (1980 to present);

• EBSCO CINAHL (1982 to present)

We will search the Cochrane Central Register of Controlled Trials (CENTRAL) using the following exploded MeSH headings and keywords:

#1 MeSH descriptor Chest Tubes explode all trees #2 MeSH descriptor Thoracostomy explode all trees #3 (chest or thora*) NEAR/3 (tube* or drain*):ti,ab,kw #4 (#1 OR #2 OR #3) #5 MeSH descriptor Anti‐Bacterial Agents explode all trees #6 MeSH descriptor Cephalosporins explode all trees #7 cefacetrile or cefadroxil or cephalexin or cefaloglycin or cefalonium or cefaloridine or cefalotin or cefapirin or cefatrizine or cefazaflur or cefazedone or cefazolin or cefradine or cefroxadine or ceftezole or cefaclor or cefonicid or cefprozil or cefuroxime or cefuzonam or cefmetazole or cefotetan or cefoxitin or cefcapene or cefdaloxime or cefdinir or cefditoren or cefetamet or cefixime or cefmenoxime or cefodizime or cefotaxime or cefovecin or cefpimizole or cefpodoxime or cefteram or ceftibuten or ceftiofur or ceftiolene or ceftizoxime or ceftriaxone or cefoperazone or ceftazidime or cefclidine or cefepime or cefluprenam or cefoselis or cefozopran or cefpirome or cefquinome:ti,ab,kw #8 MeSH descriptor Antibiotic Prophylaxis explode all trees #9 antibiotic* NEAR/3 prophyl*:ti,ab,kw #10 antibiotic* NEAR/3 premedication*:ti,ab,kw #11 presumptive NEXT antibiotic*:ti,ab,kw #12 (#5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11) #13 (#4 AND #12)

We will adapt this strategy to search Ovid MEDLINE, Ovid EMBASE and EBSCO CINAHL. We will combine Ovid MEDLINE search with the Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE: sensitivity‐ and precision‐maximizing version (2008 revision) (Lefebvre 2009). We will combine the EMBASE and CINAHL searches with the trial filters developed by the Scottish Intercollegiate Guidelines Network (SIGN 2010). There will be no restrictions on the basis of date or language of publication.

Searching other resources

We will search the bibliographies of all retrieved and relevant publications identified by these strategies for further studies. We will try to identify possibly relevant studies reported in conference abstracts through specialist database sources and by hand‐searching or electronically searching those abstracts. This will be done by searching British Library Direct Plus: www.bl.uk/reshelp/docsupply/productsservices/bldplus and ISI Proceedings: scientific.thomson.com/products/proceedings.

Data collection and analysis

Selection of studies

We will identify titles and abstracts of papers using the search strategy set out above and two review authors (CJR and PEOC) will screen these independently. We will obtain full copies of potentially eligible studies. Two review authors (CJR and PEOC), acting independently, will decide on final inclusion or exclusion of studies, based on predefined inclusion and exclusion criteria. We will resolve disagreements by discussion and if this does not result in consensus, the third review author's opinion will be decisive. We will document the reasons for exclusion of any article from selection.

Data extraction and management

Two review authors will independently extract details of eligible studies and summarise them using a data extraction sheet. This summary will contain the baseline characteristics of study and control group participants and include their number, age, gender, ethnicity, surgery type, interventions and prespecified outcomes of interest (e.g. surgical site infection). Furthermore, we will extract details of the intervention studied, plus the content of the total programme (co‐interventions) and details of the control intervention. We will also record the healthcare setting in which the interventions were performed. In addition we will extract duration of follow up and numbers lost to follow up as well as outcomes. Where more than one publication has arisen from a study, we will extract data from all relevant publications, though not from duplicated papers. Two review authors (CJR and PEOC) will extract all data regarding the interventions studied independently. We will resolve disagreements by discussion. If this does not result in consensus, the third review author’s opinion will be decisive. One review author will enter the data into RevMan (RevMan 2008) and this will be checked by a second review author.

Assessment of risk of bias in included studies

We will assign two review authors (CJR and PEOC) to assess each study independently using the Cochrane Collaboration tool for assessing risk of bias (Higgins 2009a). This tool addresses six specific domains, namely sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting and other issues (e.g. extreme baseline imbalance) (see Appendix 3 for details of the criteria on which the judgement will be based). We will assess blinding and completeness of outcome data for each outcome separately. We will complete a 'Risk of bias' table for each eligible study. We will calculate initial disagreement of judgement per domain and express it as percentage agreement (Brennan 1992). We will discuss any disagreement in a consensus meeting. We will present assessment of risk of bias using a 'Risk of bias' summary figure, which presents all of the judgements in a cross‐tabulation of study by entry. This display of internal validity indicates the weight the reader may give to the results of the particular studies.

Measures of treatment effect

Depending on the available data and event rate, we will present the results for binary outcomes (e.g. infection, mortality) as risk ratios (RR) with corresponding 95% confidence intervals (CI). We will present continuous data (e.g. duration of hospitalisation) as mean differences (MD) with corresponding 95% CIs or standardised mean difference (SMD), with 95% CIs for outcomes such as knowledge and behaviour scores where different scores are used.

Unit of analysis issues

Comparisons that randomise or allocate clusters (e.g. clinics) but do not account for clustering during analysis have potential unit of analysis errors resulting in artificially low P values and over‐narrow confidence intervals. We will attempt to re‐analyse studies with potential unit of analysis errors by calculating effective sample sizes where possible (Higgins 2009b). If a comparison is re‐analysed then the P value will be quoted and annotated, with ‘re‐analysed’. If this is not possible we will report only the point estimate (Donner 2001). If trials include multiple intervention groups receiving a complex intervention, as defined above, we will split the shared control group into two or more groups with smaller sample size, depending on the number of interventions studied, and include two or more comparisons (Higgins 2009b).

Dealing with missing data

If data are missing from the trial reports, we will attempt to contact the trial authors to request these values. If this is not successful, we will make an assumption as to whether the data are missing 'at random' or 'not at random'. In the first case we will only analyse the available data, ignoring the missing data. In the latter case the only way to compare data by meta‐analysis may be by imputing replacement values. If this is necessary, we will perform sensitivity analyses to assess how sensitive results are to reasonable changes in the assumptions that are made. Furthermore, we will also address the potential impact of missing data on the findings of the review in the Discussion section (Higgins 2009b).

Assessment of heterogeneity

We will consider clinical heterogeneity and a group of studies may be amenable to meta‐analysis if study population (age and baseline risk of infection) and the interventions studied are sufficiently similar. If this is the case, we will first assess statistical heterogeneity using the I² statistic (Higgins 2003) which examines the percentage of total variation across studies due to heterogeneity rather than to chance. Values of I² under 25% indicate a low level of heterogeneity and justify use of a fixed‐effect model for meta‐analysis. Values of I² between 25% and 75% are considered moderate and a random‐effects model can be used. Values of I² higher than 75% indicate high level of heterogeneity and pooling will not be undertaken. I² should be used as a guide in the interpretation of the evidence and not as an absolute measure to make major decisions (Ioannidis 2007).

Assessment of reporting biases

We will assess reporting bias graphically by means of a funnel plot. We will report separately for each primary outcome. However, it must be recognised that if the number of eligible studies is small the results are likely to be inconclusive (Egger 1997).

Data synthesis

In the event of substantial statistical heterogeneity between studies (values of I² higher than 75%) we will presented a qualitative summary (O'Rourke 1989). Where possible we will group the studies together where the interventions are similar. We will discuss both the effectiveness of complex interventions on the whole and the contribution of individual components of complex interventions. For low levels of heterogeneity (values of I² under 25%) we will use a fixed‐effect model for meta‐analysis for any appropriate pooling. If statistical heterogeneity is moderate (values of I² between 25% and 75%), we will use a random‐effects model for meta‐analysis (Deeks 2009).

Subgroup analysis and investigation of heterogeneity

We will perform meta‐regression analysis to observe the effect of the following possible sources of variation among studies on the outcomes: clean and clean‐contaminated surgical interventions (Deeks 2009).

Sensitivity analysis

We will perform a sensitivity analysis to determine the effect of study risk of bias on our results (Deeks 2009). We will classify studies as low risk of bias if allocation was concealed, if bias due to non‐blinding is unlikely and if incompleteness of outcome data is adequately addressed.

Appendices

Appendix 1. Criteria for defining a surgical site infection (SSI) (Horan 1992)

Superficial incisional SSI

Infection occurs within 30 days after the operation and infection involves only skin or subcutaneous tissue of the incision and at least one of the following:

1. purulent drainage, with or without laboratory confirmation, from the superficial incision;

2. organisms isolated from an aseptically obtained culture of fluid or tissue from the superficial incision;

3. at least one of the following signs or symptoms of infection: pain or tenderness, localised swelling, redness or heat and superficial incision is deliberately opened by surgeon, unless incision is culture‐negative;

4. diagnosis of superficial incisional SSI by the surgeon or attending physician.

Do not report the following conditions as SSI:

1. stitch abscess (minimal inflammation and discharge confined to the points of suture penetration);

2. infection of an episiotomy or newborn circumcision site;

3. infected burn wound;

4. incisional SSI that extends into the fascial and muscle layers (see deep incisional SSI).

Note: specific criteria are used for identifying infected episiotomy and circumcision sites and burn wounds.

Deep incisional SSI

Infection occurs within 30 days after the operation if no implant is left in place or within one year if implant is in place and the infection appears to be related to the operation and infection involves deep soft tissues (e.g. fascial and muscle layers) of the incision and at least one of the following:

1. purulent drainage from the deep incision but not from the organ/space component of the surgical site;

2. a deep incision spontaneously dehisces or is deliberately opened by a surgeon when the patient has at least one of the following signs or symptoms: fever (> 38 ºC), localised pain or tenderness, unless site is culture‐negative;

3. an abscess or other evidence of infection involving the deep incision is found on direct examination, during reoperation or by histopathologic or radiologic examination;

4. diagnosis of a deep incisional SSI by a surgeon or attending physician.

Notes:

1. Report infection that involves both superficial and deep incision sites as deep incisional SSI.

2. Report an organ/space SSI that drains through the incision as a deep incisional SSI.

Organ/space SSI

Infection occurs within 30 days after the operation if no implant is left in place or within one year if implant is in place and the infection appears to be related to the operation and infection involves any part of the anatomy (e.g. organs or spaces), other than the incision, which was opened or manipulated during an operation and at least one of the following:

1. purulent drainage from a drain that is placed through a stab wound into the organ/space;

2. organisms isolated from an aseptically obtained culture of fluid or tissue in the organ/space;

3. an abscess or other evidence of infection involving the organ/space that is found on direct examination, during reoperation or by histopathologic or radiologic examination;

4. diagnosis of an organ/space SSI by a surgeon or attending physician.

Appendix 2. Surgical Wound Classification (Garner 1985; Simmons 1982)

Class I/clean

An uninfected operative wound in which no inflammation is encountered and the respiratory, alimentary, genital or uninfected urinary tract is not entered. In addition, clean wounds are primarily closed and, if necessary, drained with closed drainage. Operative incisional wounds that follow non‐penetrating (blunt) trauma should be included in this category if they meet the criteria.

Class II/clean‐contaminated

An operative wound in which the respiratory, alimentary, genital or urinary tracts are entered under controlled conditions and without unusual contamination. Specifically, operations involving the biliary tract, appendix, vagina and oropharynx are included in this category, provided no evidence of infection or major break in technique is encountered.

Class III/contaminated

Open, fresh, accidental wounds. In addition, operations with major breaks in sterile technique (e.g. open cardiac massage) or gross spillage from the gastrointestinal tract, and incisions in which acute, non‐purulent inflammation is encountered are included in this category.

Class IV/dirty‐infected

Old traumatic wounds with retained devitalised tissue and those that involve existing clinical infection or perforated viscera. This definition suggests that the organisms causing postoperative infection were present in the operative field before the operation.

Appendix 3. 'Risk of bias' table judgement criteria

1.  Was the allocation sequence randomly generated?

Low risk of bias

The investigators describe a random component in the sequence generation process such as: referring to a random number table; using a computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots.

High risk of bias

The investigators describe a non‐random component in the sequence generation process. Usually, the description would involve some systematic, non‐random approach, for example: sequence generated by odd or even date of birth; sequence generated by some rule based on date (or day) of admission; sequence generated by some rule based on hospital or clinic record number.

Unclear

Insufficient information about the sequence generation process to permit judgement of low or high risk of bias.

2.  Was the treatment allocation adequately concealed?

Low risk of bias

Participants and investigators enrolling participants could not foresee assignment because one of the following, or an equivalent method, was used to conceal allocation: central allocation (including telephone, web‐based and pharmacy‐controlled randomisation); sequentially‐numbered drug containers of identical appearance; sequentially‐numbered, opaque, sealed envelopes.

High risk of bias

Participants or investigators enrolling participants could possibly foresee assignments and thus introduce selection bias, such as allocation based on: using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or non opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.

Unclear

Insufficient information to permit judgement of low or high risk of bias. This is usually the case if the method of concealment is not described or not described in sufficient detail to allow a definite judgement, for example if the use of assignment envelopes is described, but it remains unclear whether envelopes were sequentially numbered, opaque and sealed.

3.  Blinding ‐ was knowledge of the allocated interventions adequately prevented during the study?

Low risk of bias

Any one of the following.

• No blinding, but the review authors judge that the outcome and the outcome measurement are not likely to be influenced by lack of blinding.

• Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

• Either participants or some key study personnel were not blinded, but outcome assessment was blinded and the non‐blinding of others unlikely to introduce bias.

High risk of bias

Any one of the following.

• No blinding or incomplete blinding, and the outcome or outcome measurement is likely to be influenced by lack of blinding.

• Blinding of key study participants and personnel attempted, but likely that the blinding could have been broken.

• Either participants or some key study personnel were not blinded, and the non‐blinding of others likely to introduce bias.

Unclear

Any one of the following.

• Insufficient information to permit judgement of low or high risk of bias.

• The study did not address this outcome.

4.  Were incomplete outcome data adequately addressed?

Low risk of bias

Any one of the following.

• No missing outcome data.

• Reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias).

• Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.

• For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate.

• For continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size.

• Missing data have been imputed using appropriate methods.

High risk of bias

Any one of the following.

• Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups.

• For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate.

• For continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size.

• ‘As‐treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation.

• Potentially inappropriate application of simple imputation.

Unclear

Any one of the following.

• Insufficient reporting of attrition/exclusions to permit judgement of low or high risk of bias (e.g. number randomized not stated, no reasons for missing data provided).

• The study did not address this outcome.

5.  Are reports of the study free of suggestion of selective outcome reporting?

Low risk of bias

Any of the following.

• The study protocol is available and all of the study’s pre‐specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre‐specified way.

• The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre‐specified (convincing text of this nature may be uncommon)

High risk of bias

Any one of the following.

• Not all of the study’s pre‐specified primary outcomes have been reported.

• One or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre‐specified.

• One or more reported primary outcomes were not pre‐specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect).

• One or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta‐analysis.

• The study report fails to include results for a key outcome that would be expected to have been reported for such a study.

Unclear

Insufficient information to permit judgement of low or high risk of bias. It is likely that the majority of studies will fall into this category.

6.  Other sources of potential bias:

Low risk of bias

The study appears to be free of other sources of bias.

High risk of bias

There is at least one important risk of bias. For example, the study:

• had a potential source of bias related to the specific study design used; or

• had extreme baseline imbalance; or

• has been claimed to have been fraudulent; or

• had some other problem.

Unclear

There may be a risk of bias, but there is either:

• insufficient information to assess whether an important risk of bias exists; or

• insufficient rationale or evidence that an identified problem will introduce bias.

What's new

Date	Event	Description
11 December 2017	Amended	This protocol has been withdrawn as authors were unable to progress the review.

Contributions of authors

• CJ Rubira: developed the protocol and completed the first draft, contributed to and edited the protocol. Approved the final version of the protocol prior to submission.

• PE de O Carvalho: co‐ordinated the protocol development, developed, contributed to and edited the protocol. Approved the final version of the protocol prior to submission.

• AJM Cataneo: made an intellectual contribution to the protocol, part wrote and edited the document and approved the final version of the protocol prior to submission.

• LR Carvalho: made an intellectual contribution to the protocol, part wrote and edited the document and approved the final version of the protocol prior to submission.

Contributions of editorial base:

• Nicky Cullum: edited the protocol, advised on methodology, interpretation and protocol content. Approved the final protocol prior to submission. 

• Sally Bell‐Syer: co‐ordinated the editorial process. Advised on methodology, interpretation and content. Edited and copy edited the protocol.

• Ruth Foxlee: designed the search strategy and edited the search methods section.

Sources of support

Internal sources

• Evidence Based Health Actions and Thoracic Surgery, Marilia Medical School, Brazil.

External sources

• NIHR/Department of Health (England), (Cochrane Wounds Group), UK.

Declarations of interest

None known.

Notes

This protocol has been withdrawn as authors were unable to progress the review.

Withdrawn from publication for reasons stated in the review