Risk factors for early PICC removal: A retrospective study of adult inpatients at an academic medical center.

BACKGROUND: Use of PICCs has been rising since 2001. They are used when long-term intravenous access is needed and for blood draws in patients with difficult venous access.
OBJECTIVE: To determine which risk factors contribute to inappropriate PICC line insertion defined as removal of a PICC within five days of insertion for reasons other than a PICC complication.
DESIGN: Retrospective, observational study.
SETTING: Tertiary-care, Level 1 trauma center. PATIENTS: Adult patients with a PICC removed 1/1/2017 to 5/4/2020. MEASUREMENTS: Frequency of PICC removal within five days of insertion and associated risk factors for early removal.
RESULTS: Between 1/1/2017 and 5/4/2020, 995 of 5348 PICCs inserted by the IV nursing team were removed within five days (19%). In 2017, 5 of 429 PICCs developed a central line-associated infection (1.2%) and 29 of 429 PICCs developed symptomatic venous thromboembolism (6.7%). Patients with PICCs whose primary service was in an ICU were independently at higher risk of early removal (OR 1.44, 95% CI 1.14, 1.83); weekday insertion was independently associated with a lower likelihood of early removal compared to weekend insertion (OR 0.60; 95% CI 0.49, 0.75). LIMITATION: PICC removal after discharge was not assessed and paper records were likely incomplete and biased.
CONCLUSION: Nearly one in five PICCs were removed within five days. Patients whose primary team was in an ICU and PICCs ordered on weekends were at independently higher risk of early removal.

Introduction

Peripherally-inserted central catheters (PICCs) are an important component of medical care [1, 2]. They are frequently utilized when long-term intravenous (IV) access is required for antibiotic administration, medications requiring central venous access, parenteral nutrition, chemotherapy, or frequent blood draws in patients with difficult venous access [3]. Use of PICCs has been rising since 2001 due to their increased availability, ease of insertion, safety compared with central venous catheters (CVCs) inserted at other sites, and durability over extended periods of time [1, 4, 5]; however, the average dwell time for PICCs has been decreasing [5].

In hospitalized patients, insertion of a PICC for infusion of peripherally-compatible fluids, frequent phlebotomy, or difficult venous access is considered inappropriate if the expected duration of catheterization is five days or less [2]. However, infusion of irritants or vesicants such as parenteral nutrition or chemotherapy is appropriate for any proposed duration [2]. Two prospective, multi-center studies found that approximately 25% of PICCs in hospitalized patients had dwell times of five days or less [3, 6]. Known complications from PICCs include venous thromboembolism (VTE), central line-associated bloodstream infection (CLABSI), exit site infection, catheter lumen occlusion, and catheter tip migration, all of which are a cause of significant morbidity, potential mortality, and increased healthcare cost [7-11]. Placing PICCs that are removed within five days may be introducing unnecessary risk and preventable harm to a patient when there are safer alternatives [9, 10, 12, 13].

Mitigating inappropriate, short-term use of PICCs has the potential for harm reduction and cost-savings. The goals of this study were to assess: frequency and risk factors associated with PICC dwell time of five or fewer days; complications resulting from PICC use and determine if these complications were associated with the number of catheter lumens.

Methods

Study design

We performed a retrospective, observational study at Rhode Island Hospital, a tertiary-care, Level 1 trauma center licensed for 719 beds. Data were collected from two sources: paper records collected by our IV nursing team and the electronic health record (EHR). The IV nursing team is a nurse-led team that serves as a vascular access consult service throughout the hospital. The team evaluates patients for short-term peripheral venous catheters, midline catheters, and PICCs. All PICCs placed by the IV nursing team are ultrasound-guided. The IV nursing team kept paper records of PICC insertions and removals through 12/31/2017. On 1/1/2018, the IV nursing team transitioned to full utilization of the EHR. Two reviewers (BHS, LM) used the paper records from 1/1/17 to 12/31/17 to identify any patient who had a PICC removed during their hospital stay. The correct patient and hospital encounter was then identified in the EHR. We identified patient demographics and characteristics including age, sex, race, and body mass index (BMI) at the time of PICC insertion. We identified the service team overseeing the patient’s care at the time the PICC was ordered. Possible care teams included internal medicine (teaching service), hospital medicine (non-teaching service), general surgery, orthopedic surgery, neurosurgery, other medicine subspecialty, or other surgical subspecialty service. Podiatry, otolaryngology, plastic surgery, orthopedic surgery, neurosurgery, and dental surgery are all separate training programs from other surgical subspecialities. Among these, orthopedics and neurosurgery are the only ones that regularly admit patients to their service at our hospital; the other services admit to the medicine service for co-management. We hypothesized that the ordering specialty team and the day of the week would be predictors of early PICC removal.

We also identified characteristics of each PICC including number of lumens, indications for insertion and removal, order date, and time of insertion and removal. Lastly, we identified any PICC-associated complications. Symptomatic venous thromboembolism (VTE) of the extremity used for PICC placement and CLABSI were considered major complications. Symptomatic VTE was defined as any patient with a PICC who developed swelling, redness or pain that prompted imaging and which confirmed a thrombus. For CLABSI, we used the CDC National Healthcare Safety Network (CDC/NHSN) definition [14]. Minor complications included catheter occlusion, superficial thrombosis, mechanical complications such as kinking or coiling of the catheter, exit site infection, or catheter tip migration. All the information collected was recorded and stored in a REDCap database. Data from 1/1/2018 to 5/4/2020 was obtained exclusively from the EHR. Data collected during this time included patient demographic information and objective PICC data including number of lumens, order date and time, insertion date and time, and removal date and time. We were unable to obtain the service team at the time of insertion, indications for PICC insertion, or complications related to the PICC since this free text data is difficult to obtain from an automated data pull. An EHR automated data pull was also obtained for the January 2017-December 2017 time period to compare with and validate the manually collected data. The Lifespan Institutional Review Board approved this project.

Inclusion and exclusion criteria

Inpatients at least 18 years of age who had a PICC inserted by our IV nursing team on or after 1/1/2017 and removed before 5/4/2020 were included in this study. Patients were excluded if their PICC was placed at an outside hospital or by other services (e.g., interventional radiology), as these PICCs were not included in the paper records kept by the IV nursing team. The vast majority of inpatient PICCs at our facility are placed by the IV team. Central lines placed by intensive care unit teams are placed in the internal jugular, subclavian, or femoral veins. Interventional radiology is consulted for PICCs only in circumstances where the IV team is unable to successfully insert the catheter and another type of central line would not suffice. Due to the small number and unique circumstances, PICCs placed by interventional radiology were excluded from this study. PICCs removed due to complications were not excluded.

Statistical analysis

Data were imported into SAS version 9.4 (SAS Institute Inc., Cary, NC) for data management and hypothesis testing. The assessment of complications related to PICC use was based on PICCs inserted on or after 1/1/17 and removed before 12/31/17 collected from paper records. The assessment of risk factors for dwell time of five days or fewer was based on EHR data of PICCs inserted on or after 1/1/17 and removed before 5/4/20. Descriptive statistics were obtained for the study sample characteristics. Mean and standard deviation were reported for the continuous variables while frequency and percentage were reported for the binary and categorical variables. The prevalence of PICCs placed that were removed within 5 days, as well as the prevalence of major and minor PICC complications, were reported. Generalized estimating equations (GEE) were used to examine the factors associated with PICCs removed within five days of insertion (GEE with a binomial distribution and logit link). The primary factors examined were service team, day of the week that PICC insertion was ordered, and indications for PICC insertion. Patient sex, age, body mass index, race, comorbidities, number of lumens, and number of complications were considered as possible model covariates. Only those possible model covariates with p<0.05 in univariable analyses were included in the multivariable model. GEEs were also used (1) to examine which PICC complications were associated with the number of lumens (GEE with a negative binomial distribution and logit link); and (2) to examine whether the rate of early removal changed over time (GEE with a binomial distribution and logit link). Classical sandwich estimators were used to protect against possible model misspecification. A p-value < 0.05 was used to determine statistical significance.

Results

Approximately 11% of PICCs were placed in patients who were in an intensive care unit; over half of the catheters were double lumen PICCs (Table 1).

Table 1

Characteristics of patients and PICCs.

Variable	1/1/2017-12/31/2017	1/1/2017-5/4/2020
N	429	5348
Age, mean (SD)	57 (17)	59 (17)
BMI, mean (SD)	28 (10)	30 (9)
Gender, n (%)
Female	209 (49)	2524 (47)
Male	220 (51)	2824 (53)
Race, n (%)
White	324 (76)	4176 (78)
Black	37 (8.6)	497 (9.3)
Other	57 (13)	655 (12)
Unknown	11 (2.6)	20 (0.4)
Have comorbidities, n (%)	N/A	4292 (80)
PICC lumens, n (%)
1	41 (9.6)	1273 (24)
2	333 (78)	3621 (68)
3	55 (13)	454 (8.5)
Median dwell time, d (IQR)	8.0 (3.9–18)	13.0 (6.0–42)
Indication, n (%)
Antibiotics	82 (19)	N/A
Chemotherapy	14 (3.3)	N/A
Difficult venous access	157 (37)	N/A
Long-term venous access	6 (1.4)	N/A
Medications requiring central venous access	10 (2.3)	N/A
Multiple incompatible fluids	27 (6.3)	N/A
Parenteral nutrition	24 (5.6)	N/A
Unknown	31 (7.2)	N/A
Multiple	78 (18)	N/A
Service Team, n (%)
General Surgery	46 (11)	582 (19)
Hospital Surgery (non-teaching)	59 (14)	N/A
Intensive Care Unit	47 (11)	447 (15)
Internal Medicine	51 (12)	N/A
Medical Subspecialty	132 (31)	783 (26)
Neurosurgery	20 (4.7)	217 (7.1)
Orthopaedic Surgery	21 (4.9)	303 (9.9)
Other	53 (12)	731 (24)
Day of the Week, n (%)
Sunday	56 (13)	655 (12)
Monday	77 (18)	868 (16)
Tuesday	62 (15)	794 (15)
Wednesday	55 (13)	751 (14)
Thursday	60 (14)	825 (15)
Friday	62 (15)	826 (16)
Saturday	57 (13)	629 (12)
Weekend day, n (%)*	175 (41)	4064 (76)

N/A indicates that the data was not available.

*Weekend day defined as Friday, Saturday, and Sunday.

From 1/1/2017 through 12/31/2017, 141 PICCs were removed within five days of insertion. Among these 141 PICCs, 105 (74%) were removed due to reasons unrelated to complications. Complications were defined as DVT, mispositioning of the PICC, or complication arising from insertion, such as the PICC being too long or too short. From 1/1/17 through 5/4/20, 995 of 5348 PICCs were removed within five days (19%, Table 2).

Table 2

Outcomes of patients with PICCs.

Outcome	1/1/2017-12/31/2017	1/1/2017-5/4/2020
PICC removal within 5 days of insertion	141/429 (33%)	995/5348 (19%)
PICCs removed within 5 days not due to complication	105/141 (74%)	N/A
Symptomatic venous thromboembolism	29/429 (7%)	N/A
Central line-associated bloodstream infection	5/429 (1%)	N/A
Catheter occlusion	77/429 (18%)	N/A
Superficial venous thrombosis	7/429 (2%)	N/A
Mechanical complication	13/429 (3%)	N/A
Exit site infection	0/429 (0%)	N/A
Catheter tip migration	44/429 (10%)	N/A
Number without major or minor PICC complications	303/429 (71%)	N/A

N/A: Not applicable.

Intensive care units were independently associated with a higher likelihood of early PICC removal (OR 1.44, 95% CI 1.14, 1.83), while weekday insertion (Monday through Thursday) was independently associated with a lower likelihood of early removal (OR 0.60; 95% CI 0.49, 0.75, Table 3). Complications were not associated with the number of PICC lumens (Table 4). Interestingly, chemotherapy or medications requiring central access, such as those often used in intensive care units, was not a risk factor for early PICC removal. The percentage of early PICC removal by service team is displayed in Table 5.

Table 3

Multivariable model assessing associations with early PICC removal using the EHR data.

Variable	OR (95% CI)	p-value
Female	0.87 (0.72–1.05)	0.14
Age	1.01 (1.00–1.02)	0.01
BMI	1.00 (0.99–1.02)	0.44
White	0.94 (0.74–1.21)	0.64
Co-morbidity	1.03 (0.81–1.32)	0.80
Team		< .001
General Surgery	Reference
Hospital Medicine	N/A
Intensive Care Unit	2.10 (1.53–2.87)
Internal Medicine	N/A
Medical Subspecialty	1.22 (0.91–1.65)
Neurosurgery	1.06 (0.68–1.63)
Ortho Surgery	0.69 (0.44–1.09)
Other	1.06 (0.78–1.44)
PICC lumens	0.96 (0.80–1.15)	0.66
Day of week		0.001
Sunday	Reference
Monday	0.67 (0.48, 0.94)
Tuesday	0.59 (0.41, 0.83)
Wednesday	0.53 (0.36, 0.77)
Thursday	0.63 (0.44, 0.89)
Friday	0.55 (0.39, 0.79)
Saturday	0.93 (0.65, 1.33)

Table 4

Complications associated with number of PICC lumens based on 2017 manual chart review*.

Complication	IRR	95% CI	p-value
Symptomatic venous thromboembolism	1.02	(0.94, 1.11)	0.66
Central line-associated bloodstream Infection	0.88	(0.73, 1.08)	0.24
Catheter occlusion	1.04	(0.99, 1.08)	0.14
Catheter tip migration	0.99	(0.92, 1.08)	0.90
No. complications	1.02	(0.98, 1.05)	0.35

*Based on univariable GEEs and lumens treated as a count (i.e., 1, 2, or 3 PICC lumens).

Table 5

Early PICC removal by service team.

Service Team	Early PICC Removal
	1/1/2017-12/31/2017	1/1/2017-5/4/2020 (EHR Data)
General Surgery, % (95% CI)	28 (17–43)	15 (12–18)*
Hospital Medicine (non-teaching)	44 (32–57)	N/A
Intensive Care Units	21 (12–35)	27 (23–31)
Internal Medicine	33 (22–47)	N/A
Medical Subspecialty	39 (31–47)	18 (15–21)*
Neurosurgery	25 (11–48)	16 (11–21)*
Orthopedic Surgery	24 (10–46)	11 (7.8–15)*†
Other	26 (16–40)	16 (14–19)

Note: Based on univariable GEE; Post hoc pairwise comparisons between service teams were conducted within the models via orthogonal contrasts; P-values are adjusted for multiple comparisons using the Holm test.

* P<0.05 for comparisons to Intensive Care Units.

† P<0.05 for comparisons to Medicine Subspecialty.

Discussion

Nearly one in five PICCs were removed within five days, similar to prior studies. (3)

Patients whose primary team was an intensive care team were at greater risk of having early PICC removal. This is not unexpected, as a PICC may be used for chemotherapy for fewer than five days, or for critical care of a patient whose condition improves within five days of insertion. Indication for PICC insertion was only available for the 1/1/2017 to 12/31/2017 data due to limitations in procuring this data from the EHR. Approximately one in three PICC removals were on intensive care units. Aside from BMI in the univariable analysis, comorbidities as a group were not associated with earlier PICC removal. BMI has previously been shown to be associated with PICC complications, such as CLABSI [15]. We found that dwell times may differ based on day of the week, or whether it is a weekday or weekend. When the order for PICC insertion occurred on a weekday, there was a significantly lower likelihood of early PICC removal. This may reflect PICC insertion during the weekend when there was limited phlebotomy services and nursing assistance and PICC removal the following weekdays when services for peripheral IV placement and phlebotomy are more available.

We could not confirm that the number of PICC lumens is associated with increased risk of complications such as CLABSI; however, our study may have been underpowered to assess for these outcome measures [16]. Due to the retrospective design and limitations of available data, no a priori power analysis was performed. Similarly, the number of attempts for PICC placement was not readily available for all insertions and is another limitation of our dataset.

Data for this study was shared with the hospital administration leading to a change in the name of the IV team to the Vascular Access Team and a change in hospital policy occurred such that practitioners were no longer able to order PICC for insertion by the team. Instead, providers were able to order a vascular access consult so the team could assess the patient based on information provided and medical record review to make the best decision regarding the most appropriate vascular access for the patient. We are tracking vascular access to assess the impact of these changes in hopes of reducing early PICC removal and improving patient outcomes.

Our study has a number of limitations. The paper records in 2017 were incomplete due to user omission, absent medical record numbers, and difficulty with handwriting. Additionally, there is likely selection bias regarding which PICC removals were documented. It is unclear what direction the selection bias may lean towards, as there are myriad reasons why documenting could have been variable on any given day. Since the paper records did not include all patients whose PICC was removed, complications may be over or underrepresented. We only assessed PICCs that were removed during hospitalization. Thus, we did not assess the many PICCs removed from patients after hospital discharge.

Conclusion

In conclusion, weekend day orders for PICC insertion and intensive care unit teams were independent risk factors for removal of a PICC within five days. Additionally, Orthopaedic surgery had significantly fewer early PICC removals than medicine subspecialties. Further study is needed to confirm these relationships, especially to determine how weekend staffing and coverage may or may not contribute to PICC orders leading to removal within five days. Our findings may be helpful for hospital administration to reduce inappropriate PICC use.

EHR data.

(TXT)

Click here for additional data file.

REDCap data.

(TXT)

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5 Apr 2022

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Risk Factors for Early PICC Removal: A Retrospective Study of Adult Inpatients at an Academic Medical Center

This is a single centre, retrospective observational study from a large academic, trauma facility in the USA describing early removal of PICCs in a small patient sample.

There is no established power analysis reported despite its retrospective design. This makes findings difficult for generalization with other patient cohorts.

Overall, it is fairly well written, but lacks some clarity amongst some of its content.

There is no discussion regarding number of attempts to successfully place PICCs amongst the patient populations. This has been well established as a determining factor for PICC-related complications. I would consider adding this relevant data for analysis and discussion (if available), particularly if the practice was localized to just the IV Team. If data not available, this should be at least mentioned in the discussion or limitations section.

RESULTS

There is no serious contextual discussion of the results - only 4 tables with minimal sentence structure. I would consider at least providing some reporting of the results with a paragraph of text discussion, highlighting the more significant findings of the study.

TABLES

Table 1 - there is no description of any underlying co-morbidities - please provide at least discussion of influential co-morbidities that may have impacted complications or patient outcomes.

What does “Lumens, mean (SD)” mean? - what is the relevance? You have already described the subset of catheters with single and multiple lumens in the above rows. Is this different from this data? Appears a little confusing.

Change “Days in” to ‘Dwell Time’

Table 2.

Please add N/A to table legend.

Table 3.

Please complete missing data cells - Age, White (I presume you mean Race), and Comorbidity are missing reported data. If unavailable, consider removing from table and consolidating.

Team - is this describing the specialty area the patients were admitted under? What is the relevance of this data considering the inserter are a non-physician team? I do not see the benefits or relevance of this data or how it is impactful to the findings - especially when some of the data dismissing/not available.

What does the italicized REFERENCE mean in the table? Is this missing data? Please clarify.

Indications for PICC insertion are missing - how does this provide any clarity on the reason for device insertion and required therapies amongst these patient groups? This could be considered a large oversight. If no data is available, consider removing from table and discuss the lack of reported data in results or discussion section of manuscript.

Please label “P” in tables 3 & 4 as “P-Value”

CONCLUSION

Not stated

REFERENCES

11/13 (85%) >4 years old. Consider more recent scientific evidence to support your findings.

There appears to be an overuse of one authors published works 8/13 (62%), considering the scope of current literature on PICC-related outcomes that have published in the last few years focusing on specific device-related outcomes. While I acknowledge some f these works are systematic reviews, this is also more recent evidence available. I would consider the authors utilize a little more diversity across their choice of supportive clinical evidence.

Please provide DOI’s for all references wherever available, otherwise an internet link to the citation.

IMAGES

None provided.

I have several comments and questions.

Why were IR-inserted PICCs (or any other departments for that matter) excluded from this study? Surely if this large academic, trauma facility has significant numbers of inserted PICC devices, the differences between the IV team insertions and other inserter areas (e.g. IR, ICU, etc.) may possibly show differences in characteristics and outcomes between inserters, highlighting variances in patient cohorts, comorbidities and related complication rates across these clinical settings.

There is no description or model of the “IV Team” - is it an interdisciplinary team or a nurse-led team? Is it a “PICC team only”. Please consider briefly discussing the style or model of the team within the facility, as this may be influential in patient and device-related outcomes. There are a number of publications now available that describe vascular access teams function, scopes of practice and outcomes - while this may not be the authors priority, it provides an established foundation around the requirements of device insertion in the facility by the ‘team’).

There is a noticeable amount of missing data, highlighting a lack of established IV therapy/vascular access data collection processes related to PICC insertion. Specific data points are now required by most EHR’s to ensure adequate official reporting of pre- and post-procedural outcomes.

There is no reported data describing vessel characteristics (vessel choice/location, use of ultrasound guidance, measured vessel size and associated catheter to vessel ratio (CVR), or a description of insertion techniques (modified Seldinger, direct puncture, etc.), or the type of devices used (polyurethane, silicone, antimicrobial or antithrombogenic materials). These are all relative to the success or failure of device-related outcomes, whether for short, medium or long-term access. Considering the contemporary data that is frequently collected and presented in new publications, this would be considered a minimal requirement to establish the baseline variables and provide a widescreen view.

Reviewer #2: Manuscript Number: PONE-D-22-03666

Full Title: Risk Factors for Early PICC Removal: A Retrospective Study of Adult Inpatients at an

Academic Medical Center

Declaring competing interests: The reviewer declares that there are no competing interests.

Manuscript summary: The authors reviewed medical records of patients of the 5438 PICC during 40 mo. and revealed the significant risk factor for early PICC removal was medical subspeciality.

Scientific comments:

1. Background: It seems better to explain why early PICC removal is inappropriate.

2. Introduction: last paragraph

The goals of this study were to assess: frequency and risk factors associated with

catheter dwell time of five or fewer days; complications resulting from PICC use and determine if these complications were associated with the number of catheter lumens; and to assess changes in PICC dwell time during the study period.

- It would be better to bring focus on risk factors on early removal. Delete “to assess changes in PICC dwell….”. Furthermore, it was not mentioned in results.

3. Methods: Give information of PICCs, eg. French of PICC and insertion methods, by ECG guided or measurement of arm length.

4. Results Table 1. Please give the proportion of Intensive care unit vs. general ward.

5. Table 1. It seems no need to give average and SD for number of lumens.

6. Table 1. Indwelling days should be given as median and range (or interquartile). In this data, SD is much larger than the mean value which suggests that the data is more likely not a normal distribution.

7. Table 1. No. of Complications: give actual number and percentage, not mean and SD.

8. Table 2. Can the authors give number of PICC removal within 5 days and not caused by complications? That’s the primary endpoint noted at Objective..

9. Table 3. Please consider giving results of univariate analysis.

10. Table 4. Please, spell-out abbreviated words.

11. Replace gender with sex through-out manuscript, which is more bioscientific term.

12. Add conclusion at the end of Discussion, please.

Summary: This is an interesting topic and can be helpful for reduction of inappropriate use of PICC.

Although briefly mentioned in this study, lumens effect on CLABSI can be another independent topic, because generally multiple lumens have more risk of CLABSI but there is no randomized controlled study.

**********

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Reviewer #1: No

Reviewer #2: Yes: Dong Jae Shim

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17 May 2022

May 15, 2022

Marc O. Siegel, MD

Academic Editor

PLOS ONE

2150 Pennsylvania Ave NW

Washington, DC, 20037

Dear Dr. Siegel,

Thank you for reviewing and considering our manuscript. We appreciate the questions and suggested changes brought forth by the reviewers. We are submitting a tracked changes version of our manuscript as well as a clean copy.

Please see below for the reviewer comments and our response.

Sincerely,

Leonard A. Mermel, DO, ScM, AM (Hon), FSHEA, FIDSA, FACP

Professor of Medicine, Warren Alpert Medical School of Brown University

Medical Director, Dept. of Epidemiology & Infection Prevention, Lifespan Hospital System

Adjunct Clinical Professor, University of Rhode Island College of Pharmacy

There is no established power analysis reported despite its retrospective design. This makes findings difficult for generalization with other patient cohorts.

• As this was a retrospective study, we were limited by the data available. As such, no a priori power analysis was performed. We have added this limitation in the Discussion section.

There is no discussion regarding number of attempts to successfully place PICCs amongst the patient populations. This has been well established as a determining factor for PICC-related complications. I would consider adding this relevant data for analysis and discussion (if available), particularly if the practice was localized to just the IV Team. If data not available, this should be at least mentioned in the discussion or limitations section.

• This data was not available for all PICC insertions. We have added this as a limitation in the Discussion section.

RESULTS

There is no serious contextual discussion of the results - only 4 tables with minimal sentence structure. I would consider at least providing some reporting of the results with a paragraph of text discussion, highlighting the more significant findings of the study.

• We have added text highlighting the major findings of the study.

TABLES

Table 1 - there is no description of any underlying co-morbidities - please provide at least discussion of influential co-morbidities that may have impacted complications or patient outcomes.

• We had added a line describing BMI as a significant co-morbidity during univariable analysis.

What does “Lumens, mean (SD)” mean? - what is the relevance? You have already described the subset of catheters with single and multiple lumens in the above rows. Is this different from this data? Appears a little confusing.

• We agree that this part of the table was confusing and we have removed it.

Change “Days in” to ‘Dwell Time’

• We have changed “days in” to “dwell time” throughout the manuscript.

Table 2.

Please add N/A to table legend.

• We have added “N/A” to the table legend.

Table 3.

Please complete missing data cells - Age, White (I presume you mean Race), and Comorbidity are missing reported data. If unavailable, consider removing from table and consolidating.

• We understand how our original Table 3 could have presented some confusion. In that original analysis, we examined the factors associated with PICCs removed within five days of insertion. Table 3 presented the results from the multivariable analysis but did not include text necessary for interpreting the table correctly. In that original analysis, we hypothesized that service team and day of the week PICC insertion was ordered were associated early PICC removal. These variables were considered our key independent variables. Sex, age, body mass index, race, comorbidities, and number of lumens were considered as possible model covariates to be included in the multivariable model. These possible covariates were examined first in univariable models with early PICC removal (yes/no) as the outcome variable. Possible covariates were included in the multivariable model only if their univariable p-value was < 0.05, in order to preserve degrees of freedom and power. Thus, the empty rows in Table 3 corresponded to the possible covariates that did not meet our univariable criteria for inclusion in the multivariable model. The N/As in that table represented the study variables of interest that were not available in the EHR data sample.

In the revised manuscript, we refined our multivariable analyses presented in Table 3 in an effort to simplify the presentation and bring clarity to the data. In our updated multivariable analyses, we included all possible model covariates regardless of their univariable p-value. This was done, as their inclusion did not substantially alter the results and allows the reader to see that they were not significantly associated with early PICC removal.

Team - is this describing the specialty area the patients were admitted under? What is the relevance of this data considering the inserter are a non-physician team? I do not see the benefits or relevance of this data or how it is impactful to the findings - especially when some of the data is missing/not available.

• The Team describes the specialty patient care team that ordered insertion of a PICC. One of our hypotheses was that there would be a difference between the teams ordering PICC insertion and early removal. We have added the 1/1/2017 to 12/31/2017 data to Table 3 (see above for in depth discussion about changes to Table 3).

What does the italicized REFERENCE mean in the table? Is this missing data? Please clarify.

• The italicized REFERENCE is the control group against which the other groups are compared for the stastical analysis.

Indications for PICC insertion are missing - how does this provide any clarity on the reason for device insertion and required therapies amongst these patient groups? This could be considered a large oversight. If no data is available, consider removing from table and discuss the lack of reported data in results or discussion section of manuscript.

• We have added the PICC insertion indication from 1/1/2017 to 12/31/2017. Since the data in our EHR for indication is free form text, it was not available for the EHR-only data. We have added this limitation to the Discussion section.

Please label “P” in tables 3 & 4 as “P-Value”

• We have changed “P” to “P-Value.”

CONCLUSION

Not stated

• We have added a Conclusion.

REFERENCES

11/13 (85%) >4 years old. Consider more recent scientific evidence to support your findings.

There appears to be an overuse of one author’s published works 8/13 (62%), considering the scope of current literature on PICC-related outcomes that have published in the last few years focusing on specific device-related outcomes. While I acknowledge some of these works are systematic reviews, this is also more recent evidence available. I would consider the authors utilize a little more diversity across their choice of supportive clinical evidence.

• We are not aware of any data suggesting the referenced articles older than four years are out of date or less relevant. We have no relationship to Dr. Chopra, nor personal reasons to include his publications in our manuscript. Dr. Chopra is a leading investigator in PICC research and we believe the cited work is important.

Please provide DOI’s for all references wherever available, otherwise an internet link to the citation.

• We have added DOI’s to references wherever available.

Why were IR-inserted PICCs (or any other departments for that matter) excluded from this study? Surely if this large academic, trauma facility has significant numbers of inserted PICC devices, the differences between the IV team insertions and other inserter areas (e.g. IR, ICU, etc.) may possibly show differences in characteristics and outcomes between inserters, highlighting variances in patient cohorts, comorbidities and related complication rates across these clinical settings.

• The vast majority of inpatient PICCs at our facility are placed by the IV team. Central lines placed by ICU teams are placed in the internal jugular, subclavian, or femoral veins. Interventional radiology is consulted for PICC insertion only in circumstances where the IV team is unable to place the PICC and another type of central line would not suffice. Due to the small number of such events and unique circumstances, PICCs placed by interventional radiology were excluded from this study. We have added this information to the revised Methods section.

There is no description or model of the “IV Team” - is it an interdisciplinary team or a nurse-led team? Is it a “PICC team only?” Please consider briefly discussing the style or model of the team within the facility, as this may be influential in patient and device-related outcomes. There are a number of publications now available that describe vascular access teams function, scopes of practice and outcomes - while this may not be the authors priority, it provides an established foundation around the requirements of device insertion in the facility by the ‘team’).

• We have added a description of the IV team to the Study Design subsection. Evaluation of the vascular team function, scope of practice, and outcomes are beyond the scope of this study.

There is a noticeable amount of missing data, highlighting a lack of established IV therapy/vascular access data collection processes related to PICC insertion. Specific data points are now required by most EHR’s to ensure adequate official reporting of pre- and post-procedural outcomes.

• We agree and one of the motivations for this study was to examine reasons for PICC insertion and to standardize the procedure and indication for inserting PICCs. Data from this study was shared with hospital administration to adjust the process by which evaluation for PICC insertion is ordered (see revised Discussion).

There is no reported data describing vessel characteristics (vessel choice/location, use of ultrasound guidance, measured vessel size and associated catheter to vessel ratio (CVR), or a description of insertion techniques (modified Seldinger, direct puncture, etc.), or the type of devices used (polyurethane, silicone, antimicrobial or antithrombogenic materials). These are all relative to the success or failure of device-related outcomes, whether for short, medium or long-term access. Considering the contemporary data that is frequently collected and presented in new publications, this would be considered a minimal requirement to establish the baseline variables and provide a widescreen view.

• A limitation of our data set was that vessel choice/location, measured vessel size and associated catheter to vessel ratio, insertion technique were not readily available in our EHR. All PICC insertions performed by the IV team are ultrasound-guided. These factors are also beyond the scope of our manuscript as we sought to determine whether medical teams and days of the week (proxy for workflow variation) had influence of early PICC removal.

Scientific comments:

1. Background: It seems better to explain why early PICC removal is inappropriate.

• We have discussed the risks of PICCs in general and added why early PICC removal may be inappropriate to the revised Introduction section.

2. Introduction: last paragraph

The goals of this study were to assess: frequency and risk factors associated with

catheter dwell time of five or fewer days; complications resulting from PICC use and determine if these complications were associated with the number of catheter lumens; and to assess changes in PICC dwell time during the study period.

- It would be better to bring focus on risk factors on early removal. Delete “to assess changes in PICC dwell….”. Furthermore, it was not mentioned in results.

• We have removed that sentence.

3. Methods: Give information of PICCs, eg. French of PICC and insertion methods, by ECG guided or measurement of arm length.

• A limitation of our data set was that insertion methods, PICC French size, etc. were not readily available. All PICC insertions are ultrasound-guided and we have added that to the Study Design subsection.

4. Results Table 1. Please give the proportion of Intensive care unit vs. general ward.

• We have included number of intensive care unit PICC placements in revised Table 1. In addition, we have separated out intensive care unit teams and repeated the statistical analysis with this new subgroup (see above for further discussion on Table 3).

5. Table 1. It seems no need to give average and SD for number of lumens.

• We have removed the average and SD.

6. Table 1. Indwelling days should be given as median and range (or interquartile). In this data, SD is much larger than the mean value which suggests that the data is more likely not a normal distribution.

• We have changed the data to median and interquartile range.

7. Table 1. No. of Complications: give actual number and percentage, not mean and SD.

• We have removed the means and SDs and have left the number of total complications and percentages in Table 2.

8. Table 2. Can the authors give number of PICC removal within 5 days and not caused by complications? That’s the primary endpoint noted at Objective.

• We have added a line in the table to show the number of PICCs removed within 5 days that were not caused by complications. We have also added an explanation defining “complications.”

9. Table 3. Please consider giving results of univariate analysis.

• The decision on whether a variable was included in the multivariable regression model was two pronged, and depended upon whether it was a hypothesized relationship and on its univariable model results. Service team, day of the week, and indications were included in the multivariable model regardless of significance because they were hypothesized to have a relationship with the outcome (i.e., we were testing whether that relationship was true or not). For other variables, they were only retained in the multivariable model if they were statistically significant in the univariable model. All variables in the descriptive statistics section were tested as possible model predictors in the univariable models.

10. Table 4. Please, spell-out abbreviated words.

• We have spelled out abbreviated words in the revised text.

11. Replace gender with sex through-out manuscript, which is more bioscientific term.

• We have replaced “gender” with “sex” throughout the revised manuscript.

12. Add conclusion at the end of Discussion, please.

• We have added a Conclusion to the revised manuscript.

Submitted filename: PLOS ONE Response to Reviewers.docx

Click here for additional data file.

12 Jun 2022

23 Jun 2022

June 23, 2022

Marc O. Siegel, MD

Academic Editor

PLOS ONE

2150 Pennsylvania Ave NW

Washington, DC, 20037

Dear Dr. Siegel,

Thank you for reviewing and considering our manuscript. We appreciate the questions and suggested changes brought forth by the reviewers. We are submitting a tracked changes version of our manuscript and a clean copy.

Please see below for the reviewer comments and our response.

Scientific comments:

1. Abstract Results: “Patients with PICCs whose primary service was a medical subspecialty were independently at higher risk of early removal” This result should be updated according to new results.

• We have updated the abstract results.

2. Results: “In the 1/1/2017 to 12/31/2017 data set, female sex was associated with earlier PICC removal.” In this sentence, there were no p-values. Meanwhile, in table 3, female sex is not significantly associated with early removal (p=0.14). P-value of dataset of 2017 was not given. Please, clarify what lead to these results.

• We have removed this line since this was a remnant of the previous analysis.

3. Results: “Approximately one-third of PICCs were placed in patients who were in an intensive care unit” In table 1, 30.8% of patients were medicine subspeciality. ICU was 11%. There seems to be a confusion.

• We have changed it to the correct number (11%) for ICU.

4. Results: “From 1/1/2017 through 12/31/2017, 141 PICCs were removed within five days of insertion. Among these 141 PICCs, 105 (74%) were not removed due to complications.” This sentence is inappropriate. “105 (74%) were removed from unrelated to complications” would be right.

• We have made this correction.

5. Results: Table 1 shows total patient number as 7358. It should be clarified which analysis was applied for 7358 patients’ group. In results section, there seems to be no analysis on 7358 Pts. If there is no analysis on 7358, table 1 should include data of 5348 patients.

• We agree that the table and data is confusing with the 7358 total PICCs and the analysis done on the 5348 PICCs removed. We have simplified Table 1 to include just the 5348 patients with PICCs removed.

Grammar/style comments

6. Abstract Results: Between 1/1/17 and 5/4/2020 -> Between 1/1/2017 and 5/4/2020

• We have made this correction.

7. Discussion: Aside from BMI in the univariable analysis, comorbidities as a group were not associated with earlier PICC removal. BMI has previously been shown to be associated with PIC complications, such as CLABSI.[15] -> PICC

• We have made this correction.

8. Table 3. Female 0.87 (0.7201.05) -> 0.87 (0.72-1.05)

• We have made this correction.

Leonard A. Mermel, DO, ScM, AM (Hon), FSHEA, FIDSA, FACP

Professor of Medicine, Warren Alpert Medical School of Brown University

Medical Director, Department of Epidemiology & Infection Prevention, Lifespan Hospital System Adjunct Clinical Professor, University of Rhode Island College of Pharmacy

Submitted filename: PLOS ONE Response to Reviewers 2 (002).docx

Click here for additional data file.

27 Jun 2022

Risk Factors for Early PICC Removal: A Retrospective Study of Adult Inpatients at an Academic Medical Center

PONE-D-22-03666R2

Dear Dr. Mermel,

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Kind regards,

Marc O. Siegel, MD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

30 Jun 2022

PONE-D-22-03666R2

Risk Factors for Early PICC Removal: A Retrospective Study of Adult Inpatients at an Academic Medical Center

Dear Dr. Mermel:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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on behalf of

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