The effect of implementing an aseptic practice bundle for anaesthetists to reduce postoperative infections, the Anaesthetists Be Cleaner (ABC) study: protocol for a stepped wedge, cluster randomised, multi-site trial

Postoperative infection, which includes surgical site infection, pneumonia and sepsis, is a serious problem internationally with considerable human and financial costs [1, 2]. In New Zealand (NZ) alone the cost of postoperative infections exceeds NZ$136 million per year [1]. Surgical site infection occurs in up to 5% of “clean” operations [3]. Patients may face weeks with discharging wounds, time off work and re-admission to hospital [4]. In some cases, implanted artificial joints or heart valves may need to be removed and replaced. Haematogenous seeding of infection may lead to pneumonia. In the worst cases, sepsis may develop, with widespread inflammation, damage to organs and sometimes life-threatening “septic shock”.

In May 2017, the 70th World Health Assembly adopted a resolution on sepsis, urging member states “to reinforce existing strategies or develop new ones leading to strengthened infection prevention and control programmes, including… ...infection prevention practices in surgery” [5]. This followed a 2015 statement from the Lancet Infectious Diseases Commission which emphasised the global burden of sepsis and stressed global concerns over increasing pathogen resistance to antimicrobial therapies [6]. Worryingly, postoperative sepsis has increased in NZ from 7 per 1000 at-risk admissions between 2005 and 2009 to 11 per 1000 in 2013 [7]. The prevention of sepsis starts with the prevention of infections in general, notably after surgery. Thus, in NZ, reducing surgical site infection is a priority for the Health Quality & Safety Commission, the Accident Compensation Corporation, the Ministry of Health and the country’s district health boards, with national programmes implemented to this end. In 2016–2017, 28% of the Accident Compensation Corporation costs (NZ$15 million out of NZ$55 million) attributed to personal injury suffered during medical treatment were directed towards infections following surgery [8].

There is reason to believe that the burden of infective postoperative complications may not be distributed homogenously in NZ. For example, ethnic disparities in healthcare outcomes are substantial: health outcomes are, in general, worse in Māori and Pacific peoples than in their non-Māori/non-Pacific counterparts [9, 10]. Some factors identified as contributing to infection after surgery, including comorbidities such as obesity, diabetes [11] and skin infections, are more prevalent in Māori and Pacific populations [4, 12]. In addition, there could be differences in relevant aspects of their care both within hospital [13, 14] and outside hospital (e.g. access to care for wound reviews after going home from hospital). It therefore seems likely that Māori and Pacific peoples are at higher risk of postoperative infection.

Efforts to reduce postoperative infection have traditionally focussed on aspects of surgical technique and care, on hand hygiene, and on antibiotic prophylaxis. However, researchers in the United States [15‐21] have recently demonstrated that anaesthesia providers also have a direct impact on bacterial transmission and infection rates in surgical patients. It is relevant that the work of anaesthetists may be very demanding. For example, anaesthetists administer a surprisingly high number of intravenously delivered medications (on average ten injections per patient [22] and frequently more), often under considerable time pressure. Similarly, techniques involved in securing patients’ airways to ensure adequate oxygenation after the administration of neuro-muscular blocking medications may be time-critical and technically difficult. In this setting, hand hygiene and the management of contaminated airway equipment may sometimes seem secondary to other more pressing requirements to keep patients alive. Anaesthetists’ hands frequently contact patients’ saliva whilst securing the airway, and blood during the insertion of lines into veins and arteries. Hand hygiene practices may be performed less than once per hour [16]. Anecdotal observation suggests that gloves are often seen as a substitute for hand hygiene and that, under pressure of workflow, anaesthetists often move from tasks that contaminate their gloves to adjusting their anaesthetic machines, handling syringes or undertaking various other activities. Similarly, contaminated laryngoscopes and other instruments may be inadvertently returned to clean surfaces rather than designated contaminated trays. One way or another, anaesthetists can rapidly and widely contaminate their work environment [17].

Cole et al. found that 12–16% of multi-use injection ports through which medications are administered contain bacteria within 6 h [23]. Crucially, Loftus et al. have demonstrated an association between contamination of these ports and postoperative mortality [20] and transmission of pathogenic bacteria from one patient on an operating list to another, including transmission via the hands of providers and environmental surfaces [24]. Recent data from our own group [25, 26] suggest that the methods by which anaesthetists typically draw up and adminster intravenous (IV) medications during surgery may be underestimated as a contributor to postoperative infection. In highly realistic simulated surgical cases using real medications and standard practices, our group cultured gram positive, gram negative and other micro-organisms associated with postoperative infections from 5 of 38 bags (13%) of collected injectate from IV medications [25]. Then, in a clinical setting at Auckland City Hospital, we asked anaesthetists to inject their IV bolus medications via a 0.2-μm filter unit inserted into the IV line of 300 patients undergoing surgery [26]. We isolated similar micro-organisms from 6% of these filters and from 2.4% of syringes retained for possible reuse during the anaesthetics. Thus, the injection of micro-organisms into patients may arise from deficiencies in aseptic techniques in the handling of IV medications as well as from contamination of IV injection ports. Loftus et al. have investigated the use of novel devices for hand sanitisation, device disinfection, IV catheter management and stopcock design, and demonstrated reduced bacterial contamination leading to a decrease in postoperative infection [16, 19, 21]. However, these approaches may not address failures in aseptic technique during the drawing up and injecting of IV medications. All sources of infection associated with these processes could be simultaneously and substantially addressed by injecting all IV boluses of medications through a commercially available 0.2-μm filter unit of the sort often used with epidural injections. Even if the injection port on one of these units becomes contaminated, it will be proximal to a filter that is fine enough to capture most micro-organisms [27]. We have shown that it is practicable for anaesthetists to inject most IV medications through these filters, with a rated difficulty of 3 out of 10 (10 being the most difficult) [26].

Unfortunately, it is not possible to manage the commonly used anaesthetic induction agent propofol in this way. Propofol is typically provided in lipid emulsion, composed of droplets with a mean (range) size of 0.19 (0.15–0.3) μm [28], and the manufacturers (Fresenius Kabi, AstraZeneca, and AFT Pharmaceuticals) recommend that the emulsion should not be injected through microbiological filters (manufacturers’ product information sheets). This is particularly problematic, because lipid emulsions provide a rich source of nutrients for bacterial growth. An association between propofol and postoperative infections began to be reported in the early 1990s [29‐33]. In response, the then manufacturer provided an extensive educational programme for anaesthesia personnel and changed the product information to include explicit handling instructions. These instructions included using alcohol to decontaminate the neck of ampoules or rubber bungs of vials, drawing up the emulsion “aseptically”, maintaining single patient use and replacing infusion systems after 6 h [32]. Ethylenediaminetetraacetic acid (EDTA) was added to the formulation in 1996 [34]. EDTA does not prevent micro-organisms from contaminating the formulation, but it does retard their growth [35]. The product currently available in NZ does not contain any preservative and is presented in both vials and ampoules.

It seems, therefore, that a multi-faceted approach is called for to address the potential contribution of anaesthesia providers to postoperative infection. A strong precedent for the potential of a bundle of measures to reduce infection is to be found in the “Keystone Project”. This project involved strict adherence to a few simple, evidence-based practices in the insertion and subsequent management of central venous lines which substantially and sustainably reduced the median rate of catheter-related bloodstream infections per 1000 catheter days (from 2.7 pre-intervention to zero at 3 months) [36]. Widespread implementation of this bundle has been associated with reductions in mortality [37] and healthcare costs [38]. Impressive results were again obtained in a more recent study focussed on reducing catheter-associated bloodstream infections in patients with a bundle of care delivered by their intraoperative anaesthetic providers [39].

A key aspect of the “Keystone Project” was its use of the principles of implementation science [36]. Similar principles have been articulated in the recent World Health Organization publication “Guidelines on Core Components of Infection Prevention and Control Programmes” [40]. Drawing from these sources, guiding principles have been developed for this study (Table 1).

In line with principles 2, 3 and 4, we have worked collaboratively with anaesthetists, anaesthetic technicians, microbiologists and others from each of our study hospitals to develop an evidence-informed, multi-faceted practicable infection prevention bundle (see the following subsection) which combines a selection of key aseptic practices with the routine use of 0.2-μm filters for all IV bolus medications administered during anaesthesia, except propofol. We now aim to implement our bundle progressively in these institutions as a quality improvement project and to evaluate the impact of this implementation on the rate of postoperative infection.

Successful implementation of improvements in aseptic practices associated with anaesthesia has the potential to reduce postoperative infections. If this trial shows a positive change (i.e. an increase) in DAOH₉₀ after implementation of our bundle, this will add to existing evidence suggesting that the practices of anaesthesia providers are a factor in the genesis of postoperative infections, and that improved outcomes can be achieved relatively easily. The investigators are well placed to liaise with relevant organisations to promote the subsequent adoption of the bundle throughout NZ. The potential benefits in relation to reducing patient harm and the costs associated with this are substantial, and the implications for Māori and Pacific patients may be particularly important.

Our bundle was designed to be simple and practicable. Some participants in our focus groups would have liked a more comprehensive bundle, aimed at perfect aseptic practice. In our view, more substantial changes in practice would be difficult to achieve, even in the context of a trial. Asking for too much may impede the readiness of participants to accept the bundle. It is also a strength that the evidence supporting our initiative is already known to many of our participants, in part because of previous studies undertaken on this topic in Auckland. In particular, the fact that the research into the potential role of the filters was both local and recent encourages us to believe that their potential value will be readily appreciated by participants.

One reason that the more general elements of the bundle have not already been more widely embraced may be the fact that infections that follow failures in aseptic practice manifest long after anaesthesia has finished. Thus, a postoperative infection is seldom, if ever, tracked back to the source, and there is no feedback to the anaesthetists about the consequences of such failures. In practice, it is quite difficult to achieve perfect aseptic practice during the dynamic and complex conduct of anaesthesia, and there are often more immediate threats to the patient. Greater motivation to maintain asepsis is required, and providing that motivation will be a key element of this initiative. Even with greater motivation, the required improvements in practice will need to be reasonably easy to implement, and as stated, we have strived to ensure that this applies.

What if our trial produces a negative result (i.e. no statistically significant change in DAOH₉₀)? The question arises of how small a difference in DAOH₉₀ actually matters? Might we miss a small difference that actually matters? The distribution of this variable is highly skewed and reflects the fact that most patients do not become infected and so will not experience any change in this outcome. We can expect the change, if it occurs, to be seen in the DAOH₉₀ experienced by patients at lower centiles of the distribution. Thus, the difference may be more marked at the 25th percentile than at the 50th centile. With this in mind, our analysis will start by testing whether the distributions are significantly different or not (using a rank sum test tailored for a stepped wedge study that makes no assumptions about the nature of the distribution). If so, we will then provide numeric data on DAOH₉₀ at the 10th, 25th, 50th, 75th and 90th centile and graphic representation of both distributions across the entire range to show where the effect lies. This approach avoids multiple testing and at the same time allows the maximum impact to be seen clearly without having to guess at the outset where it may lie (i.e. the 10th, the 25th or some other centile). We anticipate that this approach will mitigate the risk of missing clinically important differences between our groups.

We believe that DAOH₉₀ may be a more powerful and more clinically relevant outcome measure for our study than the rate of infections per se. Nevertheless, we will utilize national databases to collect data on infections with a view to detecting any signal that will help attribute any differences in DAOH₉₀ to differences in infection.

We believe the trial is well designed to test its primary hypothesis. The findings of this trial should add substantially to our understanding of postoperative infection. The trial is a direct response to the call by the World Health Assembly for new strategies “leading to strengthened infection prevention and control programmes, including… ...infection prevention practices in surgery” [5].