TY - JOUR
AU - Brysiewicz,, P
AB - Abstract Antimicrobial stewardship (AMS) has developed over the past decade as a critical tool to promote the appropriate use of antimicrobials in order to contain antimicrobial resistance (AMR) and conserve antimicrobial medicines. Current literature supports the role of the nurse in AMR, with a strong focus on the responsibilities of the nurse in infection prevention and control (IPC), both in the formal role of the IPC nurse specialist, and the more general IPC role of the bedside nurse. There is also growing support for the collaborative role of the nurse in the multidisciplinary AMS team. There is, however, very little literature examining the clinical practice role of the nurse in AMS. In this discussion, we contend that nursing practice may unknowingly contribute to AMR owing to varying methods of administration of intermittent intravenous infusions, resulting in under-dosing of antimicrobial medicines. The development of antimicrobials dramatically changed the practice of modern medicine.1–3 It is, however, estimated that >50% of antimicrobial use within the hospital setting is inappropriate and is associated with poor patient outcomes, the development of antimicrobial resistance (AMR) and increased healthcare costs.4 In particular, the increasing use of broad-spectrum antimicrobials as empirical treatment has led to MDR organisms with fewer antimicrobial medicines available to treat the infections they cause.5,6 Antimicrobial stewardship (AMS) has become integral to healthcare settings,4,7,8 focusing on two main arms, guiding appropriate antimicrobial prescription and effective infection control,9 in order to slow the development of resistant organisms and conserve the value of existing effective antimicrobial medicines against the backdrop of a dearth of development of new agents.10 The central tenets of AMS are that ‘the right antimicrobial medicine at the right dose should be administered at the right time for the right duration’.6 Medication should not result in harm11 but antibiotics have been implicated in 22% of nurse medication errors in the ICU.12 Nursing literature indicates that intravenous (iv) administration of medicines has the potential for the greatest harm.13,14 Medication errors include not only the incorrect choice of a medication but also the incorrect preparation and administration of a correct drug.15 There is an assumption that parenteral antibiotics are reconstituted correctly, delivered on time and over the correct time period by the nurse who is administering the drug. Non-delivery of the prescribed dose may result in treatment failure. Sub-therapeutic levels of antimicrobial medicines occur when the antimicrobial concentration falls below the MIC required to kill or stop the growth of the microorganism for a prolonged period.16 Such sub-therapeutic levels at the site of infection are attributed to an incorrect prescribing dose,2 susceptibility of the pathogen,16 physiological derangements of the very ill patient16 or non-compliance with dosing intervals,12 but may also result from failure to give the complete dose. The absence of studies in the literature exploring the clinical practice of the nurse in AMS17–19 and specifically in drug administration suggests that this nurse–patient interface has been overlooked in addressing the development of AMR. To our knowledge, none of the AMS strategies to date has considered possible confounding factors introduced by the suboptimal use of iv administration sets when administering antimicrobial medicines. There is now common use of infusion ‘smart’ pumps to manage multiple iv infusions20,21 combined with secondary infusions, such as antimicrobials administered as intermittent doses, ‘piggybacked’ at a higher level in order to produce fluid flow through the system.22 Fluid movement in the iv system relies on the manipulation of pressure. A series of technical studies were initiated by the Institute for Safe Medication Practices in Canada, in order to examine nurse competency with smart-pump technology.22–24 In one of the early studies within this series, Cassano-Piché et al.22 conducted a two-part observational study in 12 hospital clinical areas into nurse management of multiple iv infusions and found that nurses demonstrated a lack of knowledge about infusion principles, attributed largely to inadequate education and training. The subsequent study conducted in a simulation laboratory designed to replicate an adult ICU observed 40 nurses who were required to perform various tasks with managing multiple infusions. Twenty nurses, allocated 60 (3 per nurse) opportunities to set up and programme pumps for multiple primary continuous iv infusions, made errors in 7 (11.7%) of the 60 attempts. Twelve (7.7%) errors were observed in a line-tracing task where 39 nurses were allocated 156 (4 per nurse) opportunities to correctly trace the infusion pathway, up from the patient access port to the pump and the iv container, using the pumps’ light linking systems. All 40 nurses were required to manage dead volume by flushing the iv tubing, with 13 (32.5%) errors observed. Twenty-five nurses were then each given one opportunity to manage the dead volume by adjusting the flush rate; 24 (96%) errors were observed. Finally, all 40 nurses were given two opportunities each to set up a secondary intermittent iv infusion, with 9 (11.3%) errors observed in the 80 attempts, and bolus programming errors found in 9 (11.5%) of 78 attempts.23 This supported a parallel study in Ontario where nurses (n=24) were asked to correct ‘planted errors’ in traditional and smart-pump technology in a simulated inpatient unit. Tasks were related to wrong drug, wrong patient, wrong dose and drugs not in the smart-pump library. An additional task (containing no planted errors) required each nurse to initiate both a maintenance infusion and a secondary ‘piggyback’ infusion across each pump type (traditional, smart and barcode). Secondary infusion errors were high across all pumps: traditional 12 (50%), smart 8 (33%) and barcode 12 (50%). Secondary infusion errors included incorrect positioning of the therapeutic bag below the maintenance fluid, resulting in reduced flow of the therapeutic fluid in 12 (37%) attempts; the clamp on the therapeutic bag line not being opened in 3 (9.38%) attempts, resulting in unintended flow of maintenance fluid at the intended rate of the therapeutic infusion; and 2 (6.25%) instances where the therapy line was connected to the wrong port of the maintenance line, allowing free flow of the medication to the patient.24 Residual volume (the volume left behind in the iv administration set at the end of the infusion) has been generally overlooked in the delivery of drugs.25,26 Studies of infusion set characteristics include management of drug incompatibilities in shared infusion space,27 peripheral line and cannula dead space when priming infusion lines,28 infusion flow rate and dead volume,29–31 back flow in delivery of ‘piggybacked’ patient-controlled analgesia,32 and flushing and locking of venous catheters.33 Little is known regarding flushing practices to clear residual volume in infusion lines25,34 and this needs to be examined in the context of the development of AMR. A Rapid Response Report (2014)35 conducted by the Canadian Agency for Drugs and Technologies in Health (CADTH) into published clinical evidence and guidelines for flushing iv tubing post-administration of medications posed the following research questions: (i) What is the clinical evidence for flushing of iv lines post-infusion of antibiotics or other medications diluted in volumes of 50 or 100 mL compared with not flushing iv lines? (ii) What are the evidence-based guidelines regarding the flushing of iv lines post-infusion of antibiotics or other medications diluted in 50 or 100 mL infusion bags? No relevant health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, non-randomized studies or evidence-based guidelines relating to these questions were found using MeSH terms ‘Humans’, ‘Flushing’, ‘Administration’ and ‘Intravenous’ within the search dates of January 2009 to January 2014.35 Lam et al (2013)36 conducted a review of the literature in order to assess piperacillin/tazobactam prolonged infusion drug losses to residual volume in iv pump lines. Search terms used were ‘tubing residuals’, ‘residual volume’, ‘residual medication’, ‘intravenous infusions’, ‘intravenous injections’, ‘piperacillin’, ‘piperacillin-tazobactam’, ‘β-lactams’, ‘equipment design’, ‘infusion pumps’, ‘extended infusion’, ‘extended administration’ and ‘prolonged infusion’. Residual volume lost to infusion pump tubing on completion of the infusion was 30 mL, resulting in under-dosing with 70% of dose delivered with the 100 mL volume bag and, more worryingly, only 40% of dose delivered with the 50 mL volume bag. The rest of the antimicrobial medication remained within the administration set unless flushed with an additional volume of 30 mL in order to clear the line. Infusion pumps automatically stop once the infusion bag is determined to be empty; 40% of the dose would therefore be delivered over a 2 h period and should flushing be adopted as nurse practice 60% of the dose would be delivered as a bolus dose, defeating the intention of a 4 h prolonged infusion. Nineteen articles met the criteria for full-text review, with three recommending increased volume, two recommending an increase from 50 to 100 mL infusion bags and the other recommending an increase from 50 to 250 mL within the non-ICU patient population.36 Intravenous infusion practices (2008 infusions in 1326 patients) in 16 NHS Trusts in the UK were observed over an 18 month period and discussed in three documents,37–39 with variability in infusion practice noted across the 16 Trusts.38 Flushing practices were documented by nurse and pharmacist observers as inconsistent and unauthorized, but accepted as local practice by nursing staff.37 Unfortunately, the protocol39 for this mixed-methods study did not allow these flushing practices to be examined in any detail37,38 and specifically excluded completed infusions even when still connected to the patient.39 An unrelated study to assess infusion volume and dose of drug discarded within administration sets,34 conducted over the period of a week in six clinical areas of a hospital in the UK, found that post-infusion flushing practices were poor, with up to 21% of the antimicrobial dose frequently discarded. Non-flushing post-infusion, observed with 84 infusions given in acute care wards, was recorded as 41/42 (97.6%) and 26/42 (61.9%) for gravity and pump infusions, respectively. Non-flushing post-infusion for both gravity and pump infusions was 117/118 (99.2%) in the surgical ward and 25/28 (89.3%) in the emergency admission ward. All patients (51/51, 100%) in the oncology wards received the full dose of the intended treatment in this study, and this was thought to be owing to strict flushing and locking of the vascular assist devices (VADs) required for long-term administration of these medications.34 Protocols for the management of these devices provided by key nursing iv therapy guidelines, Standards for Infusion Therapy (2016),21 due for revision this year by the Royal College of Nursing (RCN), and Infusion Therapy Standards of Practice (2016),40 due for revision in 2021 by the Infusion Nurses Society (INS), show recommendations for flushing and locking of VADs, in order to reduce the risk of contact between incompatible medications, and to decrease the risk of intraluminal occlusion to prolong the life of these devices. No recommendations for management of residual volume within iv lines are in either of these standard documents.21,40 Administration sets vary by manufacturer but most have priming volumes of 25–27 mL for a primary infusion line,34,41,42 with the use of extension sets and/or add-on sets and fluid required for the drip chamber creating an additional unknown volume. Non-delivery of residual volume (Table 1)43 may thus result in a potential loss of therapeutic fluid and subsequent under-dosing, which in the case of antimicrobial medicines may lead to sub-therapeutic levels. The clinical significance of this loss of volume, and therefore the loss of active compound to residual volume, especially for smaller 50 mL infusions, is unknown.44 The contribution of nursing activities regarding routine line changes, with subsequent discarding of non-administered antimicrobial medicines, to the emergence of AMR is also not known. Standard nursing recommendations are that continuous administration sets should be changed every 96 h; primary intermittent administration sets should be discarded after 24 h of use and lines should be discarded immediately if contaminated.21 Additional line changes may also occur following transfer of the patient from one department to another, for example the movement of the patient from the emergency department or the operating room to the ICU, in order to accommodate a change from gravity-feed lines to infusion pump with resulting loss of therapeutic fluid. Table 1. Potential under-dosing of antibiotics attributable to residual volume Recommended dose Recommended dilution Infusion volume Infusion volume administered to patient Drug compound administered to patient Drug compound left in iv administration set Infusion volume Infusion volume administered to patient Drug compound administered to patient Drug compound left in iv administration set Antibiotic43  piperacillin/tazobactam 4 g/0.5 g 8 hourly 50–100 mL NaCl 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60%  ampicillin 1 g 6 hourly 100 mL NaCl 100 mL 80.5 mL 80.5% 19.5% 100 mL 70 mL 70% 30%  cefazolin 1–2 g 8 hourly 50–100 mL NaCl 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60%  ertapenem 1 g daily 50 mL NaCl 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60%  imipenem 1 g 8 hourly 100 mL NaCl 100 mL 80.5 mL 80.5% 19.5% 100 mL 70 mL 70% 30%  meropenem 1 g 8 hourly NaCl no recommended volume 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60%  clarithromycin 500 mg 12 hourly 250 mL NaCl 250 mL 230.5 mL 92.2% 7.8% 250 mL 220 mL 88% 12%  vancomycin 500 mg 12 hourly 100 mL NaCl 100 mL 80.5 mL 80.5% 19.5% 100 mL 70 mL 70% 30%  colistin 360 mg 12 hourly NaCl no recommended volume 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60% Administration set 1 2 Length of set 205 cm 270 cm Volume of set 14.5 mL 25 mL Estimated volume in drip chamber ± 5 mL ± 5 mL Total fluid in iv admin line 19.5 mL 30 mL Recommended dose Recommended dilution Infusion volume Infusion volume administered to patient Drug compound administered to patient Drug compound left in iv administration set Infusion volume Infusion volume administered to patient Drug compound administered to patient Drug compound left in iv administration set Antibiotic43  piperacillin/tazobactam 4 g/0.5 g 8 hourly 50–100 mL NaCl 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60%  ampicillin 1 g 6 hourly 100 mL NaCl 100 mL 80.5 mL 80.5% 19.5% 100 mL 70 mL 70% 30%  cefazolin 1–2 g 8 hourly 50–100 mL NaCl 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60%  ertapenem 1 g daily 50 mL NaCl 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60%  imipenem 1 g 8 hourly 100 mL NaCl 100 mL 80.5 mL 80.5% 19.5% 100 mL 70 mL 70% 30%  meropenem 1 g 8 hourly NaCl no recommended volume 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60%  clarithromycin 500 mg 12 hourly 250 mL NaCl 250 mL 230.5 mL 92.2% 7.8% 250 mL 220 mL 88% 12%  vancomycin 500 mg 12 hourly 100 mL NaCl 100 mL 80.5 mL 80.5% 19.5% 100 mL 70 mL 70% 30%  colistin 360 mg 12 hourly NaCl no recommended volume 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60% Administration set 1 2 Length of set 205 cm 270 cm Volume of set 14.5 mL 25 mL Estimated volume in drip chamber ± 5 mL ± 5 mL Total fluid in iv admin line 19.5 mL 30 mL Open in new tab Table 1. Potential under-dosing of antibiotics attributable to residual volume Recommended dose Recommended dilution Infusion volume Infusion volume administered to patient Drug compound administered to patient Drug compound left in iv administration set Infusion volume Infusion volume administered to patient Drug compound administered to patient Drug compound left in iv administration set Antibiotic43  piperacillin/tazobactam 4 g/0.5 g 8 hourly 50–100 mL NaCl 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60%  ampicillin 1 g 6 hourly 100 mL NaCl 100 mL 80.5 mL 80.5% 19.5% 100 mL 70 mL 70% 30%  cefazolin 1–2 g 8 hourly 50–100 mL NaCl 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60%  ertapenem 1 g daily 50 mL NaCl 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60%  imipenem 1 g 8 hourly 100 mL NaCl 100 mL 80.5 mL 80.5% 19.5% 100 mL 70 mL 70% 30%  meropenem 1 g 8 hourly NaCl no recommended volume 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60%  clarithromycin 500 mg 12 hourly 250 mL NaCl 250 mL 230.5 mL 92.2% 7.8% 250 mL 220 mL 88% 12%  vancomycin 500 mg 12 hourly 100 mL NaCl 100 mL 80.5 mL 80.5% 19.5% 100 mL 70 mL 70% 30%  colistin 360 mg 12 hourly NaCl no recommended volume 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60% Administration set 1 2 Length of set 205 cm 270 cm Volume of set 14.5 mL 25 mL Estimated volume in drip chamber ± 5 mL ± 5 mL Total fluid in iv admin line 19.5 mL 30 mL Recommended dose Recommended dilution Infusion volume Infusion volume administered to patient Drug compound administered to patient Drug compound left in iv administration set Infusion volume Infusion volume administered to patient Drug compound administered to patient Drug compound left in iv administration set Antibiotic43  piperacillin/tazobactam 4 g/0.5 g 8 hourly 50–100 mL NaCl 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60%  ampicillin 1 g 6 hourly 100 mL NaCl 100 mL 80.5 mL 80.5% 19.5% 100 mL 70 mL 70% 30%  cefazolin 1–2 g 8 hourly 50–100 mL NaCl 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60%  ertapenem 1 g daily 50 mL NaCl 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60%  imipenem 1 g 8 hourly 100 mL NaCl 100 mL 80.5 mL 80.5% 19.5% 100 mL 70 mL 70% 30%  meropenem 1 g 8 hourly NaCl no recommended volume 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60%  clarithromycin 500 mg 12 hourly 250 mL NaCl 250 mL 230.5 mL 92.2% 7.8% 250 mL 220 mL 88% 12%  vancomycin 500 mg 12 hourly 100 mL NaCl 100 mL 80.5 mL 80.5% 19.5% 100 mL 70 mL 70% 30%  colistin 360 mg 12 hourly NaCl no recommended volume 50 mL 30.5 mL 61% 39% 50 mL 20 mL 40% 60% Administration set 1 2 Length of set 205 cm 270 cm Volume of set 14.5 mL 25 mL Estimated volume in drip chamber ± 5 mL ± 5 mL Total fluid in iv admin line 19.5 mL 30 mL Open in new tab Ensuring that the right antimicrobial medicine at the right dose is administered at the right time for the right duration is contingent upon the choice and optimal management of the iv administration set and is unequivocally within the purview of the nurse. Influential AMR and AMS documents2,4,45–53 offer no guidelines to direct nurse administration of iv antibiotics, despite concerns raised within several of these documents2,46,52 about nurses’ capabilities of managing possible drug incompatibilities with multiple infusions,46 and nurses’ expertise with extended/prolonged infusions.2,52 Furthermore, recommendations for nurse administration of antimicrobial medicines are regrettably absent from AMR and AMS position papers from nursing bodies,54 or given as very broad instructions by the RCN (2014)55 and, more recently, the American Nurses Association (2017),56 the International Council of Nurses (2017)57 and the Canadian Nurses Association.58 Examples include ‘dispensing antibiotics at the right time and under the optimal circumstances required to maintain therapeutic levels’,55 ‘the nurse receives the orders, reviews dose/time for accuracy, checks for allergy, and administers and records the antibiotics’,56 nurses ‘work with the multidisciplinary team to ensure the appropriate use of antimicrobials including selection, dose, duration, administration and therapeutic outcomes’57 and ‘the nurse has a responsibility to administer and oversee medication administration’.58 It is estimated that only 1% of articles on AMR and AMS are within nursing literature18 and are limited to either the advocacy or the infection prevention and control role of the nurse. Correct antimicrobial use is necessary to reduce selection pressure for AMR and current literature supports the view that under-dosing is as problematic as over-use in terms of the development of AMR.16,59 The role of the nurse in the administration of iv infusions of antimicrobial medicines and the contribution that non-delivery of therapeutic fluid may make to the development of AMR does not appear to have been examined. Extensive research has shown that dose optimization is an important AMS strategy, with the goal of curing the infection while reducing resistance due to sub-therapeutic drug exposure. Ensuring administration of the full dose should be added to other important dose optimization considerations, such as patient characteristics (age, weight, renal function etc.), the causative organism, the site of infection and pharmacokinetic and pharmacodynamic characteristics of the antimicrobial medicine.16,60 Conclusions AMR emerges as a result of selection pressure that occurs when pathogens are exposed to antimicrobial medicines. This association is complex and related to medical, pharmacy and nursing practice in terms of prescribing, dispensing and administering antimicrobial medicines. Increasing bacterial resistance is an issue that has great significance for the effective management of patients. The absence of clear directions, within nursing iv therapy standards and from nursing associations, for full iv delivery of antimicrobial medicines suggests that under-dosing may be a result of uninformed and inconsistent clinical practice. The literature currently does not show whether antimicrobial infusion practices contribute to treatment failure, and to AMR. It is important that every effort is made by healthcare professionals to examine protocols and procedures within their scopes of practice to identify areas that may contribute to AMR. Further investigations are required to establish the influence of nurse antimicrobial infusion practices upon potential under-dosing, and to determine best practice guidelines for full dose delivery of parenteral antimicrobial medicines. Funding No funding was received. Transparency declarations S. Essack is the chairperson of the Global Respiratory Infection Partnership sponsored by an unrestricted educational grant from Reckitt and Benckiser (Pty.), UK. All other authors: none to declare. References 1 File T , Srinivasan A , Bartlett J. Antimicrobial stewardship: importance for patient and public health . Clin Infect Dis 2014 ; 59 Suppl 3 : S93 – 6 . 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TI - Are nursing infusion practices delivering full-dose antimicrobial treatment?
JF - Journal of Antimicrobial Chemotherapy
DO - 10.1093/jac/dkz365
DA - 2019-12-01
UR - https://www.deepdyve.com/lp/oxford-university-press/are-nursing-infusion-practices-delivering-full-dose-antimicrobial-HYAJa8QxC0
SP - 3418
VL - 74
IS - 12
DP - DeepDyve
ER -