AbstractObjectiveFluids administered as drug diluents with intravenous (IV) medicine constitute a substantial fraction of fluids in inpatients. Whether physicians are aware of fluid volumes administered with IV antibiotics for patients with suspected infections is unclear. Moreover, whether this leads to adjustments in 24-hour fluid administration/antibiotics is unknown.
MethodsThis cross-sectional interview-based study was conducted in three emergency departments. Physicians were interviewed after prescribing around-the-clock IV antibiotics for ≥24 hours to patients with suspected infection. A structured interview guide assessed the physicians’ awareness, considerations, and practices when prescribing IV antibiotics. The 24-hour antibiotic fluid volume was calculated.
ResultsWe interviewed 100 physicians. The 24-hour fluid volume administered with IV antibiotics was 400 mL (interquartile range, 300–400 mL). Overall, 53 physicians (53%) were unaware of the fluid volume administered with IV antibiotics. Moreover, 76 (76%) did not account for the antibiotic fluid volume in the 24-hour fluid administration, and 96 (96%) indicated that they would not adjust prescribed fluids after receiving information about 24-hour antibiotic fluid volume administered for their patient. No comorbidities associated with fluid intolerance were the primary reason for not adjusting prescribed fluids/antibiotics. Approximately 79 (79%) opted for visibility of fluid volumes administered with IV antibiotics in the medical record.
ConclusionThe majority of physicians were unaware of fluid volumes administered as a drug diluent with IV antibiotics. The majority chose not to make post-prescribing adjustments to their planned fluid administration; they regarded their patient as fluid tolerant. The physicians opted for visibility of fluid volumes administered as diluents during the prescribing process.
INTRODUCTIONAdministration of intravenous (IV) fluids to hospitalized patients is common clinical practice and indicated for resuscitation purposes as well as nonresuscitation purposes, such as maintenance and administration of IV medication, including IV antibiotics [1–3]. The optimal fluid volume is still uncertain [4]. A liberal approach increases the risk of fluid overload, which is associated with higher mortality and morbidity [5–7]. Thus, the focus has shifted towards fluid restriction [8]. However, a recent meta-analysis of sepsis and septic shock studies did not find any differences in outcomes between restrictive and usual fluid administration [9].
Observational studies have found that a substantial proportion of fluids are given for nonresuscitation purposes, such as drug diluents for medications, including antibiotics [6,10,11]. Drug diluents are an often-overlooked fluid volume, despite being a modifiable factor in preventing fluid overload [11]. Depending on the choice of IV antibiotics, the volume of the diluting agent varies. Whether physicians are aware of the fluid volume administered as a drug diluent with prescribed IV antibiotics is unclear.
The aim of this study was to investigate whether physicians in the emergency department (ED) are aware of the fluid volume administered with the prescribed antibiotics. Furthermore, we investigated if addressing this issue would lead to adjustments in prescribed 24-hour fluid administration or choice of antibiotics.
METHODSEthics statementThe head of departments from the participating departments agreed to study participation. Each participating physician consented with a signature after an interview. Institutional Review Board approval was not required in this study.
Study designThis was a cross-sectional interview-based study with data obtained from short, structured interviews.
Study participantsThis study included 100 physicians at three EDs in Central Denmark Region: Aarhus University Hospital (n=50), Regional Hospital Viborg (n=25), and Regional Hospital Randers (n=25). A physician was eligible for an interview after prescribing around-the-clock IV antibiotics to an adult ED patient (>18 years) with suspected or confirmed infection who was planned to be admitted for at least 24 hours. Single-dose prescriptions were not included. Participation was voluntary, and data were anonymized. Each physician participant, hereafter called participant, consented with a signature after the interview and could only participate once.
The antibiotic prescribing and administration processIn the three participating departments, all IV antibiotics were prescribed by physicians in the same regional electronic patient record system. Antibiotics could be prescribed as single medications, e.g., just IV piperacillin/tazobactam, or as a regionally recommended standard prescription package containing the recommended antibiotic administration and combination for a certain presentation or infection, e.g., sepsis or pneumonia. All IV antibiotics were administered by nurses who diluted the antibiotics following the national guidelines and regional standard procedures: 100 mL of saline per antibiotic dosage, except for clarithromycin, which was diluted in 250 mL of saline (Table 1). Drug diluents and volumes were not visible in the electronic medical records during the prescribing process. If a physician had a special request in terms of fluid volume or diluent, the physician could address these to the administering nurse.
Survey development: interview design and interview questionsThe structured interview guide consisted of 13 questions (Supplementary Material 1). Initial questions assessed the characteristics of the participants: department of primary employment, clinical working experience, and rank.
The interview guide included four main questions: (1) Are you aware of the general fluid volume administered as a drug diluent with IV antibiotics? (2) Have you accounted for the fluid volume administered with the IV antibiotics when planning 24-hour fluid administration for this specific patient? (3) If you had known the total 24-hour fluid volume administered as drug diluents with IV antibiotics, would it have affected the planned 24-hour fluid administration for this specific patient? (4) Would you prefer to be made aware of the fluid volume administered with the IV antibiotics during the prescribing process?
All four questions could be responded to with either “yes” or “no.” If the participant answered “yes” to main question 2 and/or 3, several single select answer options were provided (Supplementary Material 1). The participants were provided an option to make additional comments to elaborate their perspectives.
Pilot studyTwo rounds of pilot tests were performed at the ED at Aarhus University Hospital in March 2022. Ten participants were interviewed, with five participants per pilot. Both tests were conducted face to face to detect potential ambiguity and ensure clarity during the interview.
The first pilot test revealed ambiguities in the interpretation of the questions in terms of fluid therapy versus fluids given as drug diluents and resulted in an interview briefing about the process by which IV antibiotics are diluted in saline to emphasize that our questions were solely addressing the fluid administered as a drug diluent with the IV antibiotics. The answers of these 10 participants were not included in the study.
Data collection and interview settingThe interviews were conducted from March 4 to May 17, 2022 from 12:00 AM to 11:00 PM on both weekdays and weekends. The interviewer (JA) screened the electronic medical record for ED prescriptions of around-the-clock IV antibiotics. The total 24-hour fluid volume administered as a drug diluent with the specific choice of IV antibiotic was calculated prior to the interview.
The participants were interviewed face to face at their workstation or as a walk-along interview lasting 3 to 5 minutes. The interviewer sought to find the most convenient time for the interview.
The interviewer filled out an electronic version of the interview questions real-time in Research Electronic Data Capture (REDCap) on a designated tablet while interviewing. Additional comments made by the participants throughout the interview were written down as fieldnotes and then manually entered into REDCap.
Statistical analysisDemographic data and responses are presented as numbers and proportions. The total fluid volume administered as drug diluents with IV antibiotics is presented as the median volume [12] with full and interquartile ranges. Comments from the open-ended portions of the four main questions were manually reviewed and analyzed using a thematic coding approach [13]. Thematic categories emerged when comments with similar content appeared five or more times, presented in Figs. 1–3. Consensus on the final themes was reached within the research group. All descriptive quantitative analyses were performed in Stata ver. 17 (Stata Corp).
RESULTSDemographic characteristics of the participantsOf the 100 participants interviewed, 46 (46%) were directly employed in the ED, 51 (51%) in the department of medicine, and three (3%) in the department of surgery. Furthermore, 38 participants (38%) had >10 years of working experience, 17 (17%) between 6 to 10 years, 26 (26%) between 1 to 5 years, and 19 (19%) had <1 year. The characteristics of the participants are presented in Table 2.
The total 24-hour fluid volume administered as a drug diluent with antibiotics varied between 200 and 900 mL. The median fluid volume was 400 mL (interquartile range, 300–400 mL).
Awareness of the fluid volume with IV antibioticsThe distribution of responses is presented in Table 3. In total, 53 participants (53%) were not aware of the total 24-hour fluid volume administered with the prescribed IV antibiotics. While 47 participant (47%) stated they were aware, four (4%) indicated that they usually did not reflect upon the fluid volume administered as a drug diluent during their daily practice. Furthermore, 44 (44%) were not aware that the fluid volume administered with IV antibiotics varied depending on the choice of antibiotics. Reflecting on general awareness of fluid volumes led to 28 comments (Supplementary Table 1). Of these, 21 were thematically coded as “not reflected upon during daily practice.” Six representative comments are shown in Fig. 1.
Accounting for the antibiotic fluid volumeOf the participants, 76 (76%) did not account for the fluid administered with the prescribed IV antibiotics when planning 24-hour fluid administration for their patient. The 24 participants (24%) who did account for the fluid administered with IV antibiotics made the following changes: three (3%) prescribed a 24-hour registration of fluid balance (input and output) to detect potential fluid accumulation, 12 (12%) reduced other prescribed IV fluids to account for the fluid volumes administered with IV antibiotics, and nine (9%) prescribed a 24-hour plan for fluid administration with a maximum administration of both oral and IV fluids. Of the 37 comments regarding considerations and decision-making during the prescribing process (Supplementary Table 1), 15 addressed whether the patients had comorbidities making them fluid-intolerant, which is presented as the thematic code “absence of relevant comorbidities” in Fig. 2.
Post-prescribing fluid adjustmentsA total of 96 participants (96%) chose not to make adjustments to either their prescribed antibiotic or 24-hour plan for fluid administration after being presented with the total IV antibiotic fluid volume. A total of 75 comments were given in response to this question (Supplementary Table 1); 52 were about the health status of the patient, presented as the thematic code “health status of this specific patient” in Fig. 3. Participants elaborated that they regarded their specific patient as quite healthy and able to tolerate fluids: “I am treating an uncomplicated patient, and he/she tolerates fluids. But if the patient had severe comorbidities, then it would have affected the plan.” Despite sticking to the already prescribed fluids, several participants added the following comments: “But I must admit, I am quite surprised about the fluid volume. I will keep that in mind for future prescriptions.” and “I will think about this information from now on since 400 mL can be [too] much fluid for a patient with heart disease” (Supplementary Table 1).
After being informed about total IV antibiotic fluid volumes, four participants (4%) changed their 24-hour plan of fluid administration. Of these, two had prescribed antibiotics for patients with severe pneumonia, including both IV clarithromycin and IV piperacillin/tazobactam, resulting in 900 mL of drug diluent over a 24-hour period. Both participants changed IV clarithromycin to oral intake, thereby reducing the fluid volume by 500 mL.
Improving awareness during the prescription processThe majority of participants (79%) indicated that they would prefer visibility of the fluid volumes administered as a drug diluent with IV antibiotics in the electronic medical record to improve awareness during the prescribing process. The following comments were made: “It would be very helpful if the fluid volumes administered with IV antibiotics were visible in the prescribing section of the electronic medical journal. In this way, we would become more aware while making the treatment plan and thereby preventing the potential risk of volume loading the patients, especially the patients who can’t tolerate fluid.” Participants found that the most clinically effective way of doing this would be during the prescribing process. However, some speculated that information about fluid volume used as a drug diluent could potentially confuse the prescribing physician in an emergent setting, risking delayed initial IV antibiotic treatment.
DISCUSSIONWhen prescribing IV antibiotics to ED patients with suspected infection, more than half of the participants in this study were not aware of the fluid volume administered as a drug diluent with antibiotics. Of the participants who were aware of the fluid volumes, some added that they did not give antibiotic fluids much thought when executing the prescription, emphasizing our hypothesis that physicians are not critically aware of the fluid volume administered with IV antibiotics. Furthermore, more than a third of the participants were not aware that the drug diluting volume varied depending on the choice of antibiotic.
When presented with the total fluid volume administered as a drug diluent over a 24-hour period for their specific patient, the majority did not change either their planned 24-hour fluid administration or antibiotic prescriptions, since they regarded their patient as fluid tolerant. However, several of the participants were surprised about the total fluid volume administered with IV antibiotics, stating that it was higher than expected and that they would consider the fluid volumes administered as drug diluents in their future prescriptions.
Targeting nonresuscitation fluidsThe majority of the participants did not account for the fluid volume administered with IV antibiotics, which could be because of a common misconception that fluids used as drug diluents for IV medications, including antibiotics, are unlikely to significantly contribute to fluid overload in hospitalized patients. However, several observational studies have shown that the majority of IV fluids are prescribed for nonresuscitation purposes, sometimes called the fluid creep, such as IV medications and maintenance fluids in both stable and unstable patients [5,6,11,14]. We found that fluid volumes administered as drug diluents with IV antibiotics varied between 200 and 900 mL. Data from a multicenter observational study found that fluids administered with antibiotics are a significant contributor to IV fluids in intensive care unit septic shock patients [10]. To prevent fluid overload in hospitalized patients, fluids used as drug diluents, including antibiotics, should be perceived as a relevant modifiable target.
Variations in practiceIV antibiotics are usually administered through a “piggyback” with a single dose of antibiotics diluted in saline administered within 10 to 15 minutes. According to the national clinical guidelines, the recommended diluent volume for a single dose of antibiotics is 50 to 150 mL of normal saline (Table 1) for most IV antibiotics. The EDs included in this study used a fluid volume of 100 mL per antibiotic dosage. The different options for diluting volumes for antibiotics may result in variation in practice. This is in accordance with two observational studies that found that the choice of fluid volume to be administered for nonresuscitation depended on tradition and local practice [6,10]. We did not investigate whether physicians or nurses were aware of the possibility of reducing volumes or changing diluents. Providing isotonic fluids to patients who require treatment with low-salt fluids and others who require salts could be important to consider, highlighting the potential complexities of fluid management and the importance of tailoring diluent choices to specific patient needs.
Managing and administering IV medicines, including IV antibiotics, is traditionally assigned to nurses. Since the prescribing physicians are rarely involved in the administration of IV medicine, physicians tend not to give antibiotic fluids much thought when prescribing IV antibiotics. The lack of clarity regarding who decides the volume of the drug diluent could explain why the majority of the physicians were unaware of the fluid volume administered with IV antibiotics.
Comorbidities and awarenessDespite a majority of participating physicians retaining their initially planned 24-hour fluids, there was consensus among the participants that patients with known comorbidities such as kidney and/or heart disease should be treated with a more fluid-restrictive approach. In such clinical scenarios, the participants would have accounted for all fluids including drug diluents. This is in agreement with the findings of recent fluid studies, in which a more restrictive fluid approach was observed among physicians treating patients with known heart failure or impaired kidney function, indicating a higher awareness when dealing with fluid-intolerant patients [15–17].
Change to administration route/solutionChanging the administration route from IV to oral is a potential strategy when aiming for a restrictive fluid approach. The regional antibiotic recommendation for patients with severe pneumonia includes both IV clarithromycin and IV piperacillin/tazobactam, resulting in a total of 900 mL of IV fluid in a 24-hour period. It is commonly believed that IV antibiotics are more effective than oral, but no significant difference in mortality was found when comparing oral clarithromycin with IV clarithromycin in the treatment of moderate to severe pneumonia [18]. Other studies found no differences in efficacy when comparing oral with IV antibiotics in treating bacteremia and endocarditis [19,20]. Since no evidence clearly supports IV antibiotics as superior to oral intake in all patients, the administration of IV fluids could be significantly reduced by treating some infections with oral antibiotics.
Alternatively, IV push medications (minimal diluting volumes equivalent to the size of one saline syringe) could be used. IV piperacillin/tazobactam push administration did not cause any adverse events, harm, or changes in mortality and was well-tolerated in patients with sepsis compared with IV piggybacks [21–23].
Education and nudging strategiesThe study found a lack of critical awareness when executing the prescription of IV medications, likely due to the overall limited focus on education in prescribing fluids. Junior physicians have been found to be inadequately trained to prescribe fluids [12]. Although most prevalent among junior physicians [24], Leach et al. [25] found all medical ranks to have inadequate knowledge regarding fluid management.
IV fluids should be handled with the same thoroughness as any other drug [26–28]. Awareness of prescribing IV fluids can be obtained through education, leading to a significant improvement in the accuracy and appropriateness of fluid management [29]. To achieve greater awareness among physicians, the fluid volumes administered as drug diluents when prescribing IV medications could be made visible in the electronic medical records during the prescribing process. The lack of visibility while prescribing may contribute to an underestimation of the fluid volumes administered for purposes other than resuscitation, which is why introducing subtle nudging strategies such as visualization of the fluid volume could lead to a more conscious and careful fluid administration. In general, the exigent circumstances in the EDs, with crowding and critically ill patients, challenge physicians in their decision-making processes and highlight the need for a universal, easy, visible, and transparent prescribing and administration process of IV antibiotics to decrease the fluid creep and restrict intravenous, unnecessary and potentially avoidable IV fluids.
Strengths and limitationsA strength of this study is that we interviewed a total of 100 participants, which increases both the validity and generalizability of our findings [30]. Second, the chosen study design made the interviews far less time-consuming and inconvenient for the overloaded physicians, enabling the interviewer to collect real-time data by interviewing the participants immediately after the prescription of IV antibiotics. Third, the same interviewer (JA) was used throughout the whole study, resulting in a consistent interview style.
There are three main limitations. First, all main questions in the structured interview were designed as closed ended and with simple response options (yes or no) to accommodate the time-consuming aspect, which may have resulted in less-nuanced qualitative data. Some participants, who indicated their awareness of the fluid volume administered with IV antibiotics, admitted that they did not give fluids much thought during daily practice when prescribing antibiotics, indicating a difference between being aware and being critically aware while prescribing. Hence, more response options may have led to improved accuracy of the data.
Second, the interviews took place at workstations among other working colleagues in the ED with different ranks, including higher ranked colleagues. These circumstances may have intimidated the participants, because of the risk of challenges to their credibility, clinical knowledge, and decision-making from colleagues.
Third, the main question regarding post-prescribing adjustments to their planned 24-hour fluid administration could be perceived as confrontational. It is recommended to use only neutral questions to generate genuine answers; hence, if the question had assessed future fluid prescriptions, rather than the completed prescriptions, it may have been perceived as less confrontational. Thus, we could have avoided challenging the clinical judgement of the participants, which also could explain why the majority of the physician participants stuck to their initial treatment plan.
ConclusionsA majority of physicians are not aware of the fluid volumes administered as drug diluents with IV antibiotics, highlighting a clinical issue. When presented with the total 24-hour fluid volume administered for their patient, the vast majority of participants did not make post-prescribing adjustments to their planned fluid administration or antibiotic prescriptions since their specific patient did not have relevant comorbidities associated with fluid intolerance. For future prescriptions involving drug diluents, respondents indicated that they would consider accounting for the fluid volume, and they would prefer if fluid volumes were shown during the prescribing process.
NOTESAcknowledgements
The authors would like to thank all physicians who participated in the structured interviews.
Data availability
Data analyzed in this study are available from the corresponding author upon reasonable request.
Author contributions
Conceptualization: all authors; Data curation: JA, MKJ; Formal analysis: JA, MKJ; Investigation: JA, MKJ; Methodology: all authors; Project administration: JA; Resources: MKJ; Software: JA, MKJ; Supervision: ML, MKJ; Validation: all authors; Visualization: JA, MKJ; Writing–original draft: JA; Writing–review & editing: ML, MKJ. All authors read and approved the final manuscript.
Supplementary materialsSupplementary materials are available from https://doi.org/10.15441/ceem.24.219.
Supplementary Table 1.Additional comments by the participants.
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![]() ![]() ![]() ![]() Fig. 1.Thematic coding of comments with similar content when asked about general awareness of fluid volumes administered as drug diluent with intravenous (IV) antibiotics. ![]() Fig. 2.Thematic coding of comments with similar content when asked about accounting for fluids administered with intravenous (IV) antibiotics when prescribing a 24-hour plan for fluid administration ![]() Fig. 3.Thematic coding of comments with similar content when asked about adjustments to the planned fluid administration after prescription. IV, intravenous; SPP, standard prescription package (recommended antibiotic administration for a certain presentation/infection). ![]() Table 1.Frequently used IV antibiotics, diluents, and volumes
a)As recommended by the IV guidelines (iv-vejledninger.dk). Table 2.Demographic characteristics of prescribing participants (n=100)
Table 3.Distribution of responses (n=100)
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