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Gustavsson, H., Toll, R., Fahlander, S., Meyer, F., Ölwegård, B., Hultman, M., . . . Wilhelms, D. (2026). Physiological limits of capillary refill time: a human endotoxemia study. Critical Care, 30(1), Article ID 461.
Open this publication in new window or tab >>Physiological limits of capillary refill time: a human endotoxemia study
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2026 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 30, no 1, article id 461Article in journal (Refereed) Published
Abstract [en]

Background

The capillary refill test is a widely used bedside marker of tissue perfusion, but its reliability during acute inflammation is not well characterised. The guiding 3-s threshold rests on limited physiological validation and on visual assessment with high observer variability. How finger capillary refill time (CRT) behaves during acute inflammation remains unclear. Using quantitative capillary refill time (qCRT), which removes observer variability, we determined how finger qCRT behaves over an acute inflammatory episode in a controlled human endotoxemia model.

Methods

In a double-blind, randomized, crossover study, 25 healthy volunteers received an intravenous bolus of Escherichia coli lipopolysaccharide (0.8 ng/kg) or saline placebo. Finger qCRT was measured by polarized reflectance imaging at baseline and 1.5, 3.5, and 5 h, and analysed with censored (Tobit) mixed-effects models adjusting for physiological covariates.

Results

Finger qCRT followed a biphasic course that crossed the 3-s clinical threshold in both directions within a single inflammatory episode. From a baseline near 3.5 s, it was prolonged to 8.31 s at 1.5 h, with 14 of 25 reaching the 10-s ceiling, then shortened to 1.27 s at 5 h during persisting systemic inflammation. Estimated marginal contrasts against placebo were 4.13 s and − 3.10 s at these time points (both p < 0.0001). The early prolongation persisted after adjustment for physiological covariates, whereas the late shortening was attenuated after adjustment for concurrent thermoregulatory and haemodynamic covariates. Skin temperature was the strongest qCRT covariate, with each standard-deviation increase associated with a 1.62 s decreased qCRT. No formal mediation analysis was performed. Resting values were highly variable, with between-subject differences explaining a minority of total variance (intraclass correlation 0.30).

Conclusions

Finger qCRT tracks the course of acute systemic inflammation but crosses the 3-s clinical threshold in both directions within a single episode. Because between-subject differences account for a minority of total variance and resting values depend strongly on skin temperature, a single value against a fixed threshold is unreliable, whereas change over time within a participant is informative. These findings in healthy participants are not directly generalizable to septic shock and require confirmation in prospective patient studies before informing clinical practice.

Place, publisher, year, edition, pages
Springer Nature, 2026
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-227717 (URN)10.1186/s13054-026-06247-8 (DOI)001869696100001 ()42706575 (PubMedID)2-s2.0-105049550680 (Scopus ID)
Funder
Linköpings universitet
Available from: 2026-09-18 Created: 2026-09-18 Last updated: 2026-10-01
Munir Ehrlington, S., Hörlin, E., Toll, R., Wretborn, J. & Björk Wilhelms, D. (2024). Frailty is associated with 30-day mortality: a multicentre study of Swedish emergency departments. Emergency Medicine Journal, 41(9), 514-519
Open this publication in new window or tab >>Frailty is associated with 30-day mortality: a multicentre study of Swedish emergency departments
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2024 (English)In: Emergency Medicine Journal, ISSN 1472-0205, E-ISSN 1472-0213, Vol. 41, no 9, p. 514-519Article in journal (Refereed) Published
Abstract [en]

Background Older patients living with frailty have an increased risk for adverse events. The Clinical Frailty Scale (CFS) is a 9-point frailty assessment instrument that has shown promise to identify frail emergency department (ED) patients at increased risk of adverse outcomes. The aim of this study was to investigate the association between CFS scores and 30-day mortality in an ED setting when assessments are made by regular ED staff.Method This was a prospective multicentre observational study carried out between May and November 2021 at three EDs in Sweden, where frailty via CFS is routinely assessed by ED staff. All patients &gt;= 65 years of age were eligible for inclusion. Mortality at 7, 30 and 90 days, admission rate, ED and hospital length of stay (LOS) were compared between patients living with frailty (CFS &gt;= 5) and robust patients. Logistic regression was used to adjust for confounders.Results A total of 1840 ED visits of patients aged &gt;= 65 years with CFS assessments done during the study period were analysed, of which 606 (32.9%) were patients living with frailty. Mortality after the index visit was higher in patients living with frailty at 7 days (2.6% vs 0.2%), 30 days (7.9% vs 0.9%) and 90 days (15.5% vs 2.4%). Adjusted ORs for mortality for those with frailty compared with more robust patients were 9.9 (95% CI 2.1 to 46.5) for 7-day, 6.0 (95% CI 3.0 to 12.2) for 30-day and 5.7 (95% CI 3.6 to 9.1) 90-day mortality. Patients living with frailty had higher admission rates, 58% versus 36%, a difference of 22% (95% CI 17% to 26%), longer ED LOS, 5 hours:08 min versus 4 hours:36 min, a difference of 31 min (95% CI 14 to 50), and longer in-hospital LOS, 4.8 days versus 2.7 days, a difference of 2.2 days (95% CI 1.2 to 3.0).Conclusion Patients living with frailty, had significantly higher mortality and admission rates as well as longer ED and in-hospital LOS compared with robust patients. The results confirm the capability of the CFS to risk stratify short-term mortality in older ED patients.Trial registration number NCT04877028.

Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP, 2024
Keywords
frailty; emergency department; triage; geriatrics; clinical assessment
National Category
Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:liu:diva-206308 (URN)10.1136/emermed-2023-213444 (DOI)001278779500001 ()39053972 (PubMedID)
Note

Funding Agencies|Region Ostergotland [RO-965951]

Available from: 2024-08-15 Created: 2024-08-15 Last updated: 2026-04-01Bibliographically approved
Hörlin, E., Munir Ehrlington, S., Toll, R., Henricson, J. & Wilhelms, D. (2023). Is the clinical frailty scale feasible to use in an emergency department setting? A mixed methods study. BMC Emergency Medicine, 23(1), Article ID 124.
Open this publication in new window or tab >>Is the clinical frailty scale feasible to use in an emergency department setting? A mixed methods study
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2023 (English)In: BMC Emergency Medicine, E-ISSN 1471-227X, Vol. 23, no 1, article id 124Article in journal (Refereed) Published
Abstract [en]

Background: The Clinical Frailty Scale (CFS) is a frailty assessment tool used to identify frailty in older patients visitingthe emergency department (ED). However, the current understanding of how it is used and accepted in ED clinicalpractice is limited. This study aimed to assess the feasibility of CFS in an ED setting.

Methods :This was a prospective, mixed methods study conducted in three Swedish EDs where CFS had recentlybeen introduced. We examined the completion rate of CFS assessments in relation to patient- and organisationalfactors. A survey on staff experience of using CFS was also conducted. All quantitative data were analyseddescriptively, while free text comments underwent a qualitative content analysis.

Results: A total of 4235 visits were analysed, and CFS assessments were performed in 47%. The completion rate exceeded 50% for patients over the age of 80. Patients with low triage priority were assessed to a low degree (24%). There was a diurnal variation with the highest completion rates seen for arrivals between 6 and 12 a.m. (58%). The survey response rate was 48%. The respondents rated the perceived relevance and the ease of use of the CFS with a median of 5 (IQR 2) on a scale with 7 being the highest. High workload, forgetfulness and critical illness were rankedas the top three barriers to assessment. The qualitative analysis showed that CFS assessments benefit from a clearroutine and a sense of apparent relevance to emergency care.

Conclusion: Most emergency staff perceived CFS as relevant and easy to use, yet far from all older ED patientswere assessed. The most common barrier to assessment was high workload. Measures to facilitate use may includeclarifying the purpose of the assessment with explicit follow-up actions, as well as formulating a clear routine for the assessment.

Registration: The study was registered on ClinicalTrials.gov 2021-06-18 (identifier: NCT04931472).

Place, publisher, year, edition, pages
BioMed Central (BMC), 2023
Keywords
Clinical frailty scale; Feasibility; Frailty; Implementation; Emergency medicine; Geriatric medicine; Mixed methods
National Category
Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:liu:diva-198798 (URN)10.1186/s12873-023-00894-8 (DOI)001679305700001 ()37880591 (PubMedID)2-s2.0-85174888552 (Scopus ID)
Note

Funding: Open access funding provided by Linköping University

Available from: 2023-10-30 Created: 2023-10-30 Last updated: 2026-06-12
Hörlin, E., Munir Ehrlington, S., Henricson, J., Toll, R. & Björk Wilhelms, D. (2022). Inter-rater reliability of the Clinical Frailty Scale by staff members in a Swedish emergency department setting. Academic Emergency Medicine, 29(12), 1431-1437
Open this publication in new window or tab >>Inter-rater reliability of the Clinical Frailty Scale by staff members in a Swedish emergency department setting
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2022 (English)In: Academic Emergency Medicine, ISSN 1069-6563, E-ISSN 1553-2712, Vol. 29, no 12, p. 1431-1437Article in journal (Refereed) Published
Abstract [en]

Introduction As frailty among the elderly is receiving increasing attention in emergency departments (EDs) around the world, the use of frailty assessment tools is growing. An often used such tool is the Clinical Frailty Scale (CFS), whose inter-rater reliability has been sparingly investigated in ED settings. No inter-rater reliability study regarding CFS has previously been performed within the Scandinavian ED context. The primary aim of this study was to evaluate the inter-rater reliability of the CFS in a Swedish ED setting. Methods This was a prospective observational study conducted at three Swedish EDs. Patients &gt;= 65 years were independently assessed with CFS by their responsible physician, registered nurse, and assistant nurse. Demographic information for each assessor was collected, along with frailty status (frail/not frail) on the basis of clinical judgment. Inter-rater reliability was calculated using intraclass correlation coefficient (ICC), whereas agreement of frailty assessed by CFS (dichotomized between frail/not frail, cutoff at &gt;= 5 points) versus solely by clinical judgment was calculated by using cross-tabulation. Results One-hundred patients were included. We found inter-rater reliability to be moderate to good (ICC 0.78, 95% confidence interval [CI] 0.72-0.84), regardless of whether the care team included an emergency physician (ICC 0.74, 95% CI 0.62-0.83) or an intern/resident from another specialty (ICC 0.83, 95% CI 0.74-0.89). The agreement of clinically judged frailty compared to frailty according to CFS was 84%. In the opposing cases, staff tended to assess patients as frail to a higher extent using clinical judgment than by applying CFS on the same patient. Conclusions The CFS appears to have a moderate to good inter-rater reliability when used in a clinical ED setting. When guiding clinical decisions, we advise that the CFS score should be discussed within the team. Further research needs to be performed on the accuracy of clinical judgment to identify frailty in ED patients.

Place, publisher, year, edition, pages
Wiley, 2022
National Category
Social and Clinical Pharmacy
Identifiers
urn:nbn:se:liu:diva-189772 (URN)10.1111/acem.14603 (DOI)000870039100001 ()36200372 (PubMedID)2-s2.0-85139988797 (Scopus ID)
Available from: 2022-11-08 Created: 2022-11-08 Last updated: 2025-04-28Bibliographically approved
Toll, R. (2020). To See or Not to See: A Study on Capillary Refill. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>To See or Not to See: A Study on Capillary Refill
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Assessment of the critically ill is traditionally based on vital signs (blood pressure, pulse, respiratory rate, temperature and level of consciousness). Altered vital signs are, however, late indicators of deranged hemodynamics pointing to a need for additional, more sensitive markers of circulatory compromise. In the beginning of the 20th century, the capillary refill (CR) time evolved as a possible, non-invasive adjunct to early prediction of the outcome in the critically ill. The manoeuvre entails application of blanching pressure on the skin of the finger pulp or sternum for 5 seconds. After release of the pressure, the observer estimates time in seconds for the skin to return to original colour. This time is hypothesized to reflect the dynamics of the microcirculation and its possible connection with hemodynamics. In the 1980s the “normal capillary refill time” was set to < 2 seconds and later extended to 3 seconds, without a clear scientific foundation. Naked-eye estimations of CR time met increasing scepticism in the 1990s due to subjectivity and poor prognostic value for shock or death. Several basic traits, such as age and sex, as well as ambient temperature, were also shown to independently influence the CR time. Various methods have evolved with the capability to measure CR time quantitatively, one of which is Polarisation Spectroscopy Imaging (PSI). PSI measures the Red Blood Cell (RBC) concentration in tissue (e.g. the skin) and can be used to measure CR time.

Objectives: The purpose of this study was to establish basic characteristics for quantified CR (qCR), identify possible influencing factors in healthy subjects and to investigate how this relates to current practice. We also sought to identify technical demands for transfer of the technique into clinical studies. In paper I we analysed the (qCR) time characteristics at 5 different skin sites (forehead, sternum, volar forearm, finger pulp and dorsum finger). The objective of paper II was to investigate the inter- and intra-observer variability of naked eye CR assessments of different professions, nurses, doctors and secretaries (representing laymen). In paper III we observed the effect of low ambient temperature on the qCR time in different skin sites. In paper IV, we transferred the equipment from a laboratory to a clinical setting in the Emergency Department (ED) for application on potentially critically ill patients. In this study we evaluated the most important factors determining a reliable data collection and influencing the amount of data possible to analyse.

Methods: qCR time was measured in a total of 38 volunteers and 10 patients in different skin sites (2-5 skin sites) at different ambient temperatures. PSI (TiVi 600 and 700, WheelsBridge AB, Linköping, Sweden) was used to determine the rapid temporal changes in RBC concentration in skin during the CR manoeuvre. Films using a range of the first measurements from paper I were shown for assessment to 48 observers working in the ED.

Results: In paper I we could delineate qCR curves and suggest 2 possible equivalents to the naked-eye observed CR time which we named Time to Return to Baseline 1 (tRtB1) and Time to Peak (tpk). We demonstrated differences in qCR-curves depending on skin site and possibly due to skin temperature. In paper II we showed a poor inter- and intra-observer reproducibility in visually estimating the CR time regardless of profession (clinicians or laymen). Paper III demonstrated a rapid effect of ambient temperature on qCR time in peripheral skin sites such as finger pulp. The forehead, regarded as a more central skin site was the most temperature stable site and showed least variability in qCR time as determined using tRtB1. Paper IV, a study on patients in an ED setting, yielded assayable data in 80% of the measurements. We identified critical performance parameters to address in the further development of a more robust, easy-to-use device for future validation of the possible relevance of qCR in patient triage and monitoring.

Conclusions: CR time can be quantified using PSI. Quantified CR time demonstrated a large variability between different skin sites, specifically, skin temperature was shown to be an important factor influencing qCR time, particularly at the fingertip. Naked-eye estimates of CR time were highly variable, both within and between observers. Agreement between quantified CR time and naked-eye estimates was poor. The prototypic PSI technique was feasible in a clinical setting and, with further improvements, clinical evaluation of qCR in relation to relevant patient outcomes will be possible.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2020. p. 47
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1732
National Category
Medical Laboratory Technologies
Identifiers
urn:nbn:se:liu:diva-164907 (URN)10.3384/diss.diva-164907 (DOI)9789179298913 (ISBN)
Public defence
2020-05-05, Berzeliussalen, Building 463, Campus US, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2020-04-01 Created: 2020-04-01 Last updated: 2025-02-09Bibliographically approved
Toll John, R., Henricson, J., Junker, J., Jonson, C.-O., Nilsson, G., Björk Wilhelms, D. & Anderson, C. D. (2018). A cool response: the influence of ambient temperature on capillary refill time. Journal of Biophotonics, 11(6)
Open this publication in new window or tab >>A cool response: the influence of ambient temperature on capillary refill time
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2018 (English)In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 11, no 6Article in journal (Refereed) Published
Abstract [en]

Objective

To describe the effect of low ambient temperature on skin temperature and capillary refill (CR) time in forehead, sternum and finger pulp.

Methods

An observational, nonrandomized experimental study on 15 healthy subjects (6 females) in a cold room (8°C). Outcome measures were skin temperature and quantified CR test after application of a standardized blanching pressure (9 N/cm2) using digital photographic polarization spectroscopy to generate CR times.

Results

The finger pulp showed marked temperature fall and prolonged CR times (>10 seconds). The CR registrations of the forehead and sternum were more comparable to curves observed in a control material at room temperature, and skin temperature falls were less marked. CR times were not prolonged in forehead measurements. At the sternum, some individuals showed CR times beyond guideline recommendations despite only a marginal reduction in skin temperature.

Conclusions

Low ambient temperature is a strong independent factor for CR time at peripheral sites. Reservation about sternum as a site of measurement is warranted since cold provocation produced prolonged CR times in some individuals. We found that the forehead is the most thermostable of the 3 sites and thus the preferred site to avoid ambient temperature artifact in measuring CR time.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2018
National Category
Atom and Molecular Physics and Optics
Research subject
Disaster Medicine
Identifiers
urn:nbn:se:liu:diva-145527 (URN)10.1002/jbio.201700371 (DOI)000434641700017 ()29384267 (PubMedID)
Note

Funding agencies: Socialstyrelsen; Region Ostergotland

Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2020-04-01Bibliographically approved
McNamara, P. N., O'Doherty, J., O'Connell, M.-L., Fitzgerald, B. W., Anderson, C., Nilsson, G., . . . Leahy, M. J. (2010). Tissue viability (TiVi) imaging: temporal effects of local occlusion studies in the volar forearm. Journal of Biophotonics, 3(1-2), 66-74
Open this publication in new window or tab >>Tissue viability (TiVi) imaging: temporal effects of local occlusion studies in the volar forearm
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2010 (English)In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 3, no 1-2, p. 66-74Article in journal (Refereed) Published
Abstract [en]

Tissue Viability (TiVi) imaging is a promising new technology for the assessment of microcirculation in the upper human dermis. Although the technique is easily implemented and develops large amounts of observational data, its role in the clinical workplace awaits the development of standardised protocols required for routine clinical practice. The present study investigates the use of TiVi technology in a human, in vivo, localized, skin blood flow occlusion protocol. In this feasibility study, the response of the cutaneous microcirculation after provocation on the volar surface of the forearm was evaluated using a high temporal-low spatial resolution TiVi camera. 19 healthy subjects - 10 female and 9 male - were studied after a localized pressure was applied for 5 different time periods ranging from 5 to 25 seconds. Areas corresponding to 100 x 100 pixels (2.89 cm(2)) were monitored for 60 seconds prior to, during and after each occlusion period. Our results demonstrated the removal of blood from the local area and a hyperaemic response supporting the suitability of TiVi imaging for the generation of detailed provocation response data of relevance for the physiological function of the skin microcirculation in health and disease.

Place, publisher, year, edition, pages
John Wiley & Sons, 2010
Keywords
tissue viability, TiVi, biophotonics, optical imaging, occlusion, PORH, reactive hyperaemia
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-54069 (URN)10.1002/jbio.200910061 (DOI)000274262900013 ()
Available from: 2010-02-22 Created: 2010-02-22 Last updated: 2017-12-12Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-9299-5428

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