Introduction
Antimicrobial therapy is a common treatment for various infections, with durations varying depending on the infection type and usually lasting several days [1]. More than 80% of hospitalized patients require intravenous fluids and antimicrobial therapy [2]; the most commonly used vascular access device is short peripheral intravenous catheters (short PIVCs) [3]. A prospective observational study showed that the mean indwelling time of short PIVC was 3.06 days [4], compared with 7–14 days for conventional antimicrobial therapy [5]. Consequently, approximately 44% of adult patients require more than one short PIVC to complete intravenous therapy [6], increasing the pain of repeated punctures and overall cost [7].
The use of long peripheral intravenous catheters (long PIVC) for antimicrobial therapy has recently increased. Long PIVCs are typically left in place for 5–14 days to meet the duration of antimicrobial therapy [8]. Measuring 6–15 cm (typically, 8–10 cm) in length, a long PIVC can be inserted in either superficial or deep peripheral veins via the traditional over-the-needle technique or with more advanced procedures, such as Seldinger and accelerated Seldinger techniques [9, 10, 11]. Compared to short PIVCs, long PIVCs are associated with a lower risk of catheter failure, potentially because of their length, which ensures that two-thirds of the catheter lies within the vein. This design reduces the rates of infiltration, extravasation, and dislodgment [11, 12].
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For short PIVCs, the insertion site plays a critical role in complications. Insertion at the flexion point (anterior elbow fossa, hand/wrist) was significantly associated with higher complications rates than forearm insertion [13]. Appropriate selection of the insertion site is essential for minimizing the incidence of catheter-related complications. However, the optimal insertion site for long PIVCs remains uncertain.
The European consensus on vascular access [10] recommends placing long PIVCs in the forearm or upper arm, whereas the 2024 edition of the Infusion Therapy Standards of Practice [11] suggests insertion in the forearm with the catheter tip positioned below the antecubital fossa. Nevertheless, study has indicated that inserting long PIVCs into the deep veins of the upper arm may reduce the need for multiple venous punctures and improve adherence to catheter management guidelines, further minimizing complications [14].
Based on these findings, this study aimed to compare the outcomes of forearm and upper arm catheterisation of long PIVCs during antimicrobial therapy, focusing on catheter-related complications and other key metrics.
Methods
This study was a two-arm, parallel-group, randomized controlled trial (clinical trial registration number: NCT06455228). This study was conducted among hospitalized patients at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, China, between May and July 2024. The research protocol involved assigning patients to one of the two insertion site groups to observe the relationship between the insertion site and catheter-related complications. The institutional review board of the hospital approved the research protocol in accordance, with the Declaration of Helsinki, which respects individuals and recognizes vulnerable groups. This study was approved by the hospital’s Institutional Review Board.
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Participants
A fixed-point continuous convenience sampling method was used to enroll 90 participants. The inclusion criteria were: ① antimicrobial therapy is required during hospitalization and the expected duration of intravenous infusion is at least one week; ② age 18 years or older; and ③ patients who were conscious and able to communicate normally; and ④ the ratio of catheter-to-vessel was less than 45% in both upper arm and forearm veins assessed using ultrasound examination. The exclusion criteria were: ① a history of radiotherapy, thrombosis, or trauma at the insertion site; and ② plans for discharge with the catheter during the study period. The withdrawal criteria were: ① unable to complete follow-up after catheterization for various reasons; and ② the requirement for any irritant or vesicant drugs other than antibiotics to be infused through the long PIVC [15].
Sample size
A pilot study was conducted to estimate the necessary sample size required for the main trial. Thirty patients who met the inclusion criteria were selected for the pilot study, which yielded a complication rate of 64.0% for forearm placement of long PIVCs and 28.0% for upper arm placement. Notably that data from the pilot study were not included in the final analysis.
To establish the required sample size for the definitive study, we set an alpha risk of 0.05 and a beta risk of 0.1 in a two-sided test; the total number of patients required in both groups was calculated to be at least 72, with a minimum of 36 in each group, according to the calculations using PASS 15 software. After considering external factors that could lead to loss and withdrawal, the sample size for each group was increased by 20%, resulting in 45 patients per group.
Randomization and blinding
Of the 100 eligible patients, 90 consented to participate in the study. The participants were randomized (1:1) into the experimental and control groups using a simple randomization method. A random number table was generated using the SPSS software (version 26.0) by an individual who was not involved in this study. An independent researcher distributed consecutive randomized sequences in sealed, opaque envelopes. The participants were given envelopes according to their order of enrolment. The envelopes were opened sequentially from the lowest to the highest number. The study was unblinded.
Intervention
All the participants were informed about the study, read the study’s description, and signed a consent form. Detailed history-taking, including medical history and clinical examinations, was conducted for the participants. Intravenous therapy (IV) specialists with more than 10 years of experience in peripherally inserted central catheter (PICC) practice were assigned. IV specialists are registered nurses specializing in infusion practice and pass through a certification program established by the Zhejiang Nursing Society. Long PIVCs were inserted in the upper arm of the experimental group and the forearm of the control group by IV specialists.
Catheter insertion and maintenance
A standardized procedure was followed: ① veins were assessed by using ultrasound: the insertion site was based on group assignment. Ultrasound was used to examine the intima, depth, and diameter of the vein without applying a tourniquet. ② The patient and environment were prepared for insertion by collecting supplies, and setting up a sterile field: including hand washing, placing the patient in a recumbent position, performing skin antisepsis with 2% chlorhexidine alcohol solution, and preparing a sterile field. The catheter was inserted by IV specialists in the procedure room. ③ Placement of long PIVC: a 3 Fr, 8 cm tip-opened long PIVC was inserted via traditional over-the-needle technique under an ultrasound-guide. Needleless connectors and extension were attached to the catheter after confirming the catheter was in the vein, and the catheter was stabilized using a sterile transparent dressing. ④ Maintenance: two IV specialist nurses were designated to monitor and assess catheter function daily, including the presence of redness, tenderness, swelling, or drainage at the insertion site and to recognize signs of complications. Charge nurses were responsible for maintenance until the catheter was removed, changing the transparent dressing at least every 7 days and immediately if the integrity of the dressing was compromised or if the integrity of the skin under the dressing was compromised.
Evaluation indicators and judgment criteria
Catheter-related complications were assessed including chemical phlebitis, thrombophlebitis, catheter occlusion, bleeding, catheter-related infections, and weeping. The incidence of each complication was calculated by dividing the number of patients with each complication by the total number of patients. The main outcome index was the total number of incidences of catheter-related complications, defined as the number of patients with one or more complications divided by the total number of patients. Each patient was counted as a single case, regardless of the number of complications,
The judgment criteria for each complication were: ① thrombophlebitis: pain/tenderness, erythema, swelling or palpable venous cord along the cannulated vein, and ultrasonography indicating thrombosis at the tip or around the catheter; ② other phlebitis: include chemical phlebitis, mechanical phlebitis and infectious phlebitis; ③ catheter occlusion: inability to withdraw blood or sluggish blood return, sluggish flow; resistance or inability to flush the lumen, inability to infuse fluid, and frequent occlusion alarms on the electronic infusion pump; ④ bleeding: blood exudation at the puncture site 48 h after catheterization; ⑤ catheter-related infections: this included local infection at the puncture site and catheter-related bloodstream infection, evaluated according to the corresponding diagnostic criteria in the “Infusion Therapy Standards of Practice” [11]; ⑥ weeping: the presence of liquid exudation at the insertion site.
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The first-attempt insertion success rate refers to the instances in which the needle successfully entered the target vein on the first attempt without needing to change the insertion site. This rate was calculated as the number of successful one-attempt cases divided by the total number of patients.
The procedure time was defined as the duration from the start of skin disinfection to the stabilization of the catheter with dressing.
The indwelling catheter duration refers to the number of days between the date of catheter insertion and its removal.
Data collection
The collected data were categorized into three main areas: ① baseline data: age, sex, body mass index (BMI), history of peripheral venous catheter insertion and anticoagulant drug use within one week, and the latest coagulation-related marker; ②data of insertion process: the number of attempts, procedure time, insertion site, placement vein, depth and diameter of the vein, and indwelling catheter duration; ③function of catheters: antibiotics infused via long PIVC, catheter functioning and complications.
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Before the study, we provided training on data collection and complication identification to the 2 designated IV specialists to ensure that the data were recorded to a uniform standard. The IV specialists recorded baseline data before catheterization and data on the insertion process after catheterization. Only the most recent results were recorded one week before catheterization when multiple laboratory results were available. The IV specialists assessed the intima daily using ultrasonography during the catheter retention period. They reviewed the medical orders and recorded the medication information. The final follow-up was performed at the time of catheter removal, during which the reason for the removal was also recorded.
Statistical analysis
The current study adhered to a per-protocol analysis and conducted a statistical analysis using SPSS version 26.0. Normally distributed measurement data were represented as means and standard deviations, while non-normally distributed measurement data were represented as medians and interquartile ranges (IQR). Counting data were represented as number of cases or percentages. Quantitative data were described as the number of cases, means, standard deviations, medians, and interquartile ranges, whereas categorical data were described as the number of cases and percentage of each category. Intergroup comparisons of quantitative information were performed using a group t-test (for normally distributed data) or the Wilcoxon rank-sum test (for non-normally distributed data). Categorical data were analyzed using the chi-square or Fisher’s exact tests (when the chi-square test was not applicable), and hierarchical data were analyzed using the rank sum test. All statistical tests were two-sided (α = 0.05), with a P-value of less than or equal to 0.05 considered statistically significant.
Results
Demographics and antimicrobial therapy medication
Ninety patients were included in the study and randomized into experimental and control groups of 45 patients each. A total of 7 patients failed to complete the experiment, of these, 6 needed an infusion of irritant drugs due to changes in the illness, and 1 was discharged with a catheter. Finally, 44 patients remained in the experiment group, and 39 remained in the control group, resulting in an overall withdrawal rate of 7.8% (Fig. 1). All participants contributed to a total of 126 cases of antimicrobial therapy. Among them, 12 patients in the experimental group and 8 patients in the control group were infused with irritant or vesicant drugs, and there was no significant difference between the two groups (χ2 = 0.517, P>0.05). The most commonly prescribed medications were penicillin (28.6%), cephalosporins (20.6%), and carbapenems (18.3%) (Table 1).
The characteristics were comparable between the groups, in which the diameter and depth of veins were greater in the upper arm than in the forearm, and the difference were statistically significant (P<0.001). The rest of the characteristics were not statistically significant (P > 0.05) (Table 2).
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Fig. 1
Consort diagram profile flow
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Table 1
Antimicrobial agents among 83 patients
Antibiotic prescribed | Experiment group (N = 44) | Control group (N = 39) |
|---|---|---|
Total number of infusion cases | 69(100%) | 57(100%) |
Penicillin | 23(33.3%) | 13(22.8%) |
Cephalosporins | 9(13.0%) | 17(29.8%) |
Carbapenems | 14(20.3%) | 9(15.8%) |
Tetracycline | 9(13.0%) | 7(12.3%) |
Quinolones | 6(8.7%) | 9(15.8%) |
Glycopeptides | 3(4.4%) | 1(1.8%) |
Aminoglycosides | 1(1.5%) | 0 |
Antifungal | 3(4.4%) | 0 |
Others | 1(1.5%) | 1(1.8%) |
Table 2
Comparison of patient characteristics between the two groups
Items | Experiment group (N = 44) | Control group (N = 39) | Statistic | P-value |
|---|---|---|---|---|
Age (year, Mean ± Standard Deviation) | 64.20 ± 18.60 | 63.26 ± 16.62 | 0.244a | 0.808 |
Sex (%) | 1.873b | 0.171 | ||
Male | 28(63.6) | 19(48.7) | ||
Female | 16(36.4) | 20(51.3) | ||
BMI (Mean ± Standard Deviation) | 25.66 ± 4.39 | 25.34 ± 3.74 | 0.350a | 0.727 |
History of peripheral venous catheter placement within one week (%) | 0.686b | 0.407 | ||
Yes | 34(77.3) | 27(69.2) | ||
No | 10(22.7) | 12(30.8) | ||
History of anticoagulant use within one week (%) | 0.018c | 0.893 | ||
Yes | 6(13.6) | 4(10.3) | ||
No | 38(86.4) | 35(89.7) | ||
Prothrombin time (PT) (second, Median [Interquartile Ranges]) | 13.80(13.10, 14.40) | 14.40(13.30, 14.80) | 1.091d | 0.275 |
Activated partial thromboplastin time (APTT) (second, Median [Interquartile Ranges]) | 37.36(34.03, 40.30) | 35.50(33.90, 38.20) | 1.287d | 0.198 |
International normalized ratio (INR) (Median [Interquartile Ranges]) | 1.04(1.01, 1.12) | 1.07(1.02, 1.18) | 1.627d | 0.104 |
D–Dimer (DDI) (µg/ml, Median [Interquartile Ranges]) | 0.90(0.49, 3.08) | 0.65(0.40, 2.75) | 0.215d | 0.830 |
The placement site (%) | 0.255b | 0.613 | ||
Left arm | 25(56.8) | 20(51.3) | ||
Right arm | 19(43.2) | 19(48.7) | ||
Diameter of vein (cm, Mean ± Standard Deviation) | 0.38 ± 0.10 | 0.27 ± 0.05 | 6.686a | <0.001 |
Depth of vein (cm, Mean ± Standard Deviation) | 0.64 ± 0.34 | 0.34 ± 0.15 | 5.309a | <0.001 |
Comparison of the incidence of catheter-related complications among two groups
The total observed incidence of catheter-related complications in the experiment group and the control group were 25.0% (11/44) and 66.7% (26/39), respectively. Statistically significant differences were observed between the groups (P < 0.0001) (Table 3).
No catheter-related infections were observed in any group. There were no significant differences in the incidences of catheter occlusion, bleeding, and weeping between the two groups (P > 0.05). The difference between the two groups for thrombophlebitis was statistically significant (χ2 = 17.905, P < 0.001), whereas the difference for other phlebitis was not statistically significant (P > 0.05).
Catheterization
There were no statistically significant differences between the two groups in terms of the placement site, number of puncture attempts, and procedure times (P > 0.05) (Table 3).
Table 3
Outcome measures
Items | Experiment group (N = 44) | Control group (N = 39) | Statistic | P-value |
|---|---|---|---|---|
Total complications | 11(25.0) | 26(66.7) | 14.528a | <0.001 |
Thrombophlebitis | 4(9.1) | 20(51.3) | 17.905a | <0.001 |
Other phlebitis | 0 | 4(10.3) | 2.769b | 0.096 |
Catheter occlusion | 1(2.3) | 0 | — | >0.999c |
Bleeding | 2(4.6) | 3(7.7) | 0.019b | 0.889 |
Weeping | 4(9.1) | 1(2.6) | 0.616b | 0.432 |
Number of puncture attempts (%) | — | >0.999c | ||
Once | 43(97.7) | 38(97.4) | ||
≥ 2 times | 1(2.3) | 1(2.6) | ||
The total procedure time (second, Median [Interquartile Ranges]) | 5.55(4.93, 7.48) | 6.17(5.00, 7.33) | 0.511d | 0.609 |
Indwelling catheter duration (hour, Median [Interquartile Ranges]) | 187(129, 286) | 122(96, 188) | 3.016d | 0.003 |
Indwelling catheter duration
The median catheter indwelling duration (P25–P75) for the two groups was 187(129–286) hours and 122(96–188) hours, respectively. According to the regular follow-up results, there was a statistically significant difference in the indwelling catheter duration between the two groups (Z = 3.016, P = 0.003). (Table 3). A total of 39 patients had an indwelling catheter duration for more than one week, with the longest duration being 837 h. The longest catheter indwelling durations in the experiment group and the control group was 530 h and 837 h, respectively (Table 4). Additionally, there was a statistically significant difference in the complications per 1000 catheter days between the two groups (P < 0.001) (Table 5).
Table 4
Comparison of indwelling catheter time in two groups
Time | Experiment group (N = 44) | Control group (N = 39) |
|---|---|---|
<1 week (%) | 18(40.9) | 26(66.7) |
1–2 weeks (%) | 18(40.9) | 12(30.8) |
2–3 weeks (%) | 7(15.9) | 0 |
3–4 weeks (%) | 1(2.3) | 0 |
≥ 4 weeks (%) | 0 | 1(2.6) |
Table 5
Comparison of complications per 1000 catheter days in two groups
Group | Catheter indwelling time (days) | Total complications | Complications per 1000 catheter days | ||||
|---|---|---|---|---|---|---|---|
Total | Mean ± Standard Deviation | Median [Interquartile Ranges] | Number of people | Number of cases | Number of people | Number of cases | |
Experiment group (N = 44) | 400 | 9.10 ± 4.89 | 7.79(5.38, 11.92) | 11 | 11 | 27.5 | 27.5 |
Control group (N = 39) | 259 | 6.63 ± 5.30 | 5.08(4.00, 7.83) | 26 | 28 | 100.4 | 108.1 |
Discussion
The use of long PIVCs for antibiotic infusion is increasing. However, evidence regarding the optimal insertion site and its association with complications remains unclear. The findings of this study suggest that inserting long PIVCs in the upper arm may be associated with lower complication rates and longer indwelling times during antimicrobial therapy.
Antibiotics were categorized based on the checklist developed by Manrique et al. [15]. No statistically significant difference was observed in the number of patients receiving irritant or vesicant antibiotics between the two groups (12 in the experimental group vs. 8 in the control group). Despite this, the complication rate was significantly lower in the upper arm group (25.0%) compared to the forearm group (66.7%). These findings align with previous research indicating a 0% catheter failure rate in upper arm placements compared to a 32.0% failure rate in forearm placements within seven days [16]. Thus, upper arm insertion may effectively reduce the occurrence of catheter-related complications.
The study showed that the most common complication of long PIVC was phlebitis. The incidence of phlebitis, especially thrombophlebitis, was significantly higher when a long PIVC was inserted in the forearm, which may be related to the diameter of the vein and the duration of the indwelling catheter [11, 14]. The average diameter of the forearm veins (0.27 cm) is smaller than that of the upper arm veins (0.38 cm) and the blood flow is slower. A catheter with an outer diameter too large for the vasculature with inadequate haemodilution tends to cause endothelial damage, thus increasing the risk of thrombophlebitis [11, 17]. In addition, the studies showed that the average time from catheter insertion to thrombosis diagnosis were 8.84 days and 10.00 days [18, 19]. The median indwelling catheter durations of long PIVCs in this study were 187 h (5.08 days) and 122 h (7.79 days), leading to a gradual accumulation of platelets around the catheter. This stagnation of blood flow can result in the formation of thrombi, ultimately causing thrombophlebitis [20].
The median dwell time for long PIVCs inserted in the upper arm (187 h or 7.79 days) was consistent with the studies by Gilardi [21] and Pavelkova [22]. In both studies, long PIVCs were inserted in the upper arm of difficult intravenous access (DIVA) with indwelling times of 7–9 days and 8–9 days, respectively. In contrast, the median indwelling time in the forearm (122 h or 5.08 days) was shorter, likely because of the higher complication rate necessitating earlier removal. The catheter indwelling time for patients in both groups was approximately around one week, consistent with the dwell time recommended by the " Standards of Practice for Infusion Therapy” (5–14 days). Various studies have reported varying dwell times for long PIVC catheters. For instance, a study in which long PIVCs of different lengths were inserted in patients with DIVA showed an indwelling duration of 9–10 days [23], while Fabiani’s et al. compared long PIVCs with midline catheters and found an indwelling time of up to 14 days [9]. These discrepancies highlight the need for further exploration of the dwell times of long PIVCs. Additionally, 66.7% of patients with forearm catheters were removed within one week. Conversely, 15.9% of patients with upper arm catheters left in place for 2–3 weeks compared to none patients with forearm catheters. This may be due to the high complication rate in patients with forearm catheters, which leads to earlier removal and shorter dwell time.
The depth of the upper arm vein (0.34 ± 0.15 cm) may suffice for short PIVCs if the anticipated therapy duration is less than four days. However, the upper arm veins, being deeper, are more suitable for long PIVCs, as they are situated at deeper levels. Importantly, this study found no statistically significant differences in the first-attempt insertion success rate or the total procedure time, suggesting that upper arm insertion does not increase the procedural difficulty. In addition, the first-attempt insertion success rate was similar to that reported in previous studies [24, 25], and the total procedure time was lower than that reported in a previous systematic evaluation [8]. This is possibly related to the fact that the IV specialists in this study all had more than 10 years of experience in PICC catheterization and had received extensive long PIVC procedure training before the start of the study. Therefore, it results in a higher first-attempt insertion success rate and lower complications rates [26]. Additionally, all patients included in this study had usable veins for puncture in both the upper and forearms, with a catheter-to-vessel ratio is less than 45%, which may have contributed to the higher first-attempt insertion success rate.
Limitations
Our study had several limitations. First, there were differences between the types of antibiotics administered which may have contributed to failure. However, because of the small sample size of patients, we could not analyze the effects of different drugs on catheterization outcomes. Second, there are 7 participants withdrew from the study, resulting in a final analysis sample size that was smaller than anticipated. While we employed a per-protocol analysis, this approach may have overestimated the treatment effect. Besides, it was a single study site. This single-center nature limits the generalization of our results to all practice settings.
Conclusion
Our findings suggest that long PIVCs are perhaps an option for peripherally compatible intravenous antimicrobials, and the anticipated duration of therapy is 5–14 days. Furthermore, we suggest that long PIVCs should be inserted on the upper arm, as it results in a lower thrombophlebitis rate and an optimal dwell time. Therefore, ultrasound guidance is recommended. Future studies should consider expanding the sample size to explore factors other than insertion sites.
Acknowledgements
We would like to thank the patients who participated and all the clinical workers who assisted with this study.
Declarations
Ethics approval and consent to participate
Ethical approval was obtained from the Ethics Committee of Sir Run Run Shaw Hospital (No: 20240300). Before the study began, all of the participants were informed about the purpose and process of the study, and their participation was voluntary. The guidelines of the Declaration of Helsinki (World Medical Association, 2013) were followed throughout this study. Written informed consent was obtained from all of the included participants.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
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