umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Increased Plasma Levels of Heparin-Binding Protein on Admission to Intensive Care Are Associated with Respiratory and Circulatory Failure
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Department of Anaesthesiology and Intensive Care, Östersund Hospital, Östersund, Sweden.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Department of Surgical and Perioperative Sciences, Anaesthesiology and Intensive Care, Umeå University, Umeå, Sweden.
2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, article id e0152035Article in journal (Refereed) Published
Resource type
Text
Abstract [en]

Purpose: Heparin-binding protein (HBP) is released by granulocytes and has been shown to increase vascular permeability in experimental investigations. Increased vascular permeability in the lungs can lead to fluid accumulation in alveoli and respiratory failure. A generalized increase in vascular permeability leads to loss of circulating blood volume and circulatory failure. We hypothesized that plasma concentrations of HBP on admission to the intensive care unit (ICU) would be associated with decreased oxygenation or circulatory failure.

Methods: This is a prospective, observational study in a mixed 8-bed ICU. We investigated concentrations of HBP in plasma at admission to the ICU from 278 patients. Simplified acute physiology score (SAPS) 3 was recorded on admission. Sequential organ failure assessment (SOFA) scores were recorded daily for three days.

Results: Median SAPS 3 was 58.8 (48-70) and 30-day mortality 64/278 (23%). There was an association between high plasma concentrations of HBP on admission with decreased oxygenation (p<0.001) as well as with circulatory failure (p<0.001), after 48-72 hours in the ICU. There was an association between concentrations of HBP on admission and 30-day mortality (p = 0.002). ROC curves showed areas under the curve of 0,62 for decreased oxygenation, 0,65 for circulatory failure and 0,64 for mortality.

Conclusions: A high concentration of HBP in plasma on admission to the ICU is associated with respiratory and circulatory failure later during the ICU care period. It is also associated with increased 30-day mortality. Despite being an interesting biomarker for the composite ICU population it's predictive value at the individual patient level is low.

Place, publisher, year, edition, pages
2016. Vol. 11, no 3, article id e0152035
Keywords [en]
Biomarkers, Blood Proteins, Organ Dysfunction Scores
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:umu:diva-120365DOI: 10.1371/journal.pone.0152035ISI: 000372701200089PubMedID: 27007333OAI: oai:DiVA.org:umu-120365DiVA, id: diva2:928774
Available from: 2016-05-16 Created: 2016-05-16 Last updated: 2019-09-12Bibliographically approved
In thesis
1. Heparin-binding protein and organ failure in critical illness
Open this publication in new window or tab >>Heparin-binding protein and organ failure in critical illness
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: For patients severely ill enough to require care in an intensive care unit (ICU), both the disease itself (e.g. bacteria in the blood in sepsis or fractures after trauma) and effects of the immune system can cause circulatory, pulmonary, or renal dysfunction. Leukocytes play a dominant role in the immune system.  When activated they release a range of small proteins with different properties Heparin-binding protein (HBP) being one of these proteins, has many functions, including to increase vascular permeability. Heparin-binding protein causes plasma leakage from blood vessels into surrounding tissue (oedema), which can lead to  organ dysfunction depending on the site and degree of oedema formation. Increased concentration of HBP in plasma is associated with failing circulation and lung function in subgroups of critically ill patients.

Aims: We investigated the possibility of using concentration of HBP in plasma for predicting circulatory, respiratory or renal failure in an ICU population with mixed diagnosis. We assessed concentration of HBP in alveoli in ventilator induced lung injury (VILI), and finally assessed elimination of HBP in urine and effluent fluid from continuous dialysis.

Methods: In Papers I and II, HBP concentration in plasma was measured in 278 patients on admission to ICU. Sequential organ failure assessment (SOFA) scores and acute kidney injury (AKI) stage were recorded daily. In Paper III HBP concentration in bronco-alveolar fluid was measured in a pig model of ventilatory induced lung injury, in 16 healthy volunteers and in 10 intubated ICU patients. In Paper IV plasma and urine concentration of HBP was measured in 8 healthy volunteers and 20 burn ICU patients. In addition, HBP was sampled in plasma and effluent fluid in 32 ICU patients on continuous renal replacement therapy (CRRT).

Results: In Paper I, patients developing circulatory failure (circulatory sub-score of SOFA = 4) had higher plasma concentration of HBP compared to those who did not (median(IQR)ng/ml) (63.5(32–105) vs 36.4(24–59)) p<0.01), and patients developing respiratory failure (P:F ratio < 27) had higher HBP concentration than those who did not (44.4(30-109) vs 35.2(23-57) p<0.01). Discriminatory capacity was (ROC AUC (95%CI)) (0.65 (0.54–0.76)) for circulatory failure and (0.61(0.54–0.69)) for respiratory failure. In Paper II, patients developing renal failure (AKI stage 2-3) had higher plasma concentration of HBP compared to those who did not (72.1 (13.0–131.2) vs 34.5 (19.7–49.3) p<0.01). Discriminatory capacity for AKI stage 3 was 0.68(0.54-0.83) (ROC AUC (95%CI)). In the subgroup with severe sepsis, it was  0.93 (0.85–1.00). In Paper III, HBP concentration in bronchoalveolar lavage was higher in pigs subjected to injurious ventilation over 6 hours ventilation compared to controls (1144(359–1636) vs 89(33–191) p=0.02) (median(IQR)ng/ml). The median HBP concentration in bronchoalveolar lavage from healthy volunteers was 0.90(0.79– 1.01) compared to 1959(612–3306) from intubated ICU patients (p < 0.01).In Paper IV, renal clearance of HBP was 0.19 (0.08-0.33) in healthy individuals and 0.30 (0.01-1.04)  (median, IQR, ml/min)  in burn ICU patients. Clearance of HBP was higher in burn patients with increased cystatin C (0.45(0.15-2.81) vs. 0.28(0.14-0.55) p=0.04). Starting CRRT did not alter plasma concentration of HBP (p=0.14). Median HBP concentration in effluent fluid on CRRT was 9.1 ng/ml (7.8-14.4).

Conclusions: Papers I and II:There is an association between high concentration of HBP in plasma on ICU admission and circulatory, respiratory and renal failure. For the individual patient, the predictive value of a high HBP concentration is low, with the possible exception of renal failure in septic patients. Paper III:HBP concentration in alveoli increases in pigs subjected to injurious ventilation. HBP concentration in alveoli of intubated ICU patients ventilated protectively is elevated to similar levels, a factor of approximately 1000 times higher than the concentration seen in healthy controls. Paper IV:In healthy study participants, renal clearance of HBP is low. In critically ill burn patients with impaired renal function, clearance of HBP is increased. Starting CRRT in critically ill patients does not alter plasma concentration of HBP. Still, HBP is found in the CRRT effluent fluid, and concentration does not appear to be dependent on plasma concentration.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2019. p. 50
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2039
Keywords
Heparin-binding protein, Critical care, Shock, Acute respiratory distress syndrome, Acute kidney injury, Ventilator induced lung injury, Renal clearance
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology
Identifiers
urn:nbn:se:umu:diva-162915 (URN)978-91-7855-083-8 (ISBN)
Public defence
2019-10-11, Hörsalen Snäckan, Östersunds sjukhus, Östersund, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2019-09-20 Created: 2019-09-02 Last updated: 2019-09-18Bibliographically approved

Open Access in DiVA

fulltext(762 kB)156 downloads
File information
File name FULLTEXT01.pdfFile size 762 kBChecksum SHA-512
69995582a87ad4bccdda7859abba4db03a9c2b726a5c5cf80ae8e6d3df25ca20844d74a63015e9f43ee8642e1cff995de70c6ed7499c0b1849055478e9e0a105
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Tydén, JonasJohansson, Joakim

Search in DiVA

By author/editor
Tydén, JonasJohansson, Joakim
By organisation
Anaesthesiology
In the same journal
PLoS ONE
Radiology, Nuclear Medicine and Medical Imaging

Search outside of DiVA

GoogleGoogle Scholar
Total: 156 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 269 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf