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  • 1. Grauman, Sven
    et al.
    Boethius, Jakob
    Johansson, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Department of Anaesthesia and Intensive Care, Östersund Hospital, Östersund, Sweden.
    Regional Anaesthesia Is Associated with Shorter Postanaesthetic Care and Less Pain Than General Anaesthesia after Upper Extremity Surgery2016In: Anesthesiology Research and Practice, ISSN 1687-6962, E-ISSN 1687-6970, article id 6308371Article in journal (Refereed)
    Abstract [en]

    Introduction: For surgery on the upper extremity, the anaesthetist often has a choice between regional anaesthesia (RA) and general anaesthesia (GA). We sought to investigate the possible differences between RA and GA after upper extremity surgery with regard to postoperative patient comfort. Methods: This is a retrospective observational study that was performed at an acute care secondary referral centre. One hundred and eighty-seven procedures involving orthopaedic surgery on the upper extremity were included. The different groups (RA and GA) were compared regarding the primary outcome variable, length of stay in Postanaesthesia Unit, and secondary outcome variables, opioid consumption and nausea treatment. Results: RA was associated with significantly shorter median length of stay (99 versus 171 minutes). In the GA group, 32% of the patients received opioid analgesics and 21% received antiemetics. In the RA group, none received opioid analgesics and 3% received antiemetics. Conclusion: In this observational study, RA was superior to GA for surgery of the upper extremity regarding Postanaesthesia Care Unit length of stay, number of doses of analgesic, and number of doses of antiemetic administered.

  • 2.
    Johansson, Joakim
    et al.
    Department of Anaesthesiology and Intensive Care, Östersund Hospital, Östersund, Sweden; Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Brattström, O
    Sjöberg, F
    Lindbom, L
    Herwald, H
    Weitzberg, E
    Oldner, A
    Heparin-binding protein (HBP): an early marker of respiratory failure after trauma?2013In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 57, no 5, p. 580-586Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Trauma and its complications contribute to morbidity and mortality in the general population. Trauma victims are susceptible to acute respiratory distress syndrome (ARDS) and sepsis. Polymorphonuclear leucocytes (PMNs) are activated after trauma and there is substantial evidence of their involvement in the development of ARDS. Activated PMNs release heparin-binding protein (HBP), a granule protein previously shown to be involved in acute inflammatory reactions. We hypothesised that there is an increase in plasma HBP content after trauma and that the increased levels are related to the severity of the trauma or later development of severe sepsis and organ failure (ARDS).

    METHODS AND MATERIAL: We investigated HBP in plasma samples within 36 h from trauma in 47 patients admitted to a level one trauma centre with a mean injury severity score (ISS) of 26 (21-34). ISS, admission sequential organ failure assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were recorded at admission. ARDS and presence of severe sepsis were determined daily during intensive care.

    RESULTS: We found no correlation between individual maximal plasma HBP levels at admission and ISS, admission SOFA or APACHE II. We found, however, a correlation between HBP levels and development of ARDS (P = 0.026, n = 47), but not to severe sepsis.

    CONCLUSION: HBP is a potential biomarker candidate for early detection of ARDS development after trauma. Further research is required to confirm a casual relationship between plasma HBP and the development of ARDS.

  • 3.
    Johansson, Joakim
    et al.
    Department of Anesthesiology and Intensive care, Östersund Hospital, the Research and Development Unit, Jämtland County Council, Östersund, Sweden; Department of Anesthesiology and Intensive Care, Östersund Hospital, Research and Development Unit, Jämtland County Council, Östersund, Sweden; .
    Bäckryd, Emmanuel
    Granerus, Göran
    Sjöberg, Folke
    Urinary excretion of histamine and methylhistamine after burns2012In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 38, no 7, p. 1005-1009Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The increased vascular permeability seen after burn contribute to morbidity and mortality as it interferes with organ function and the healing process. Large efforts have been made to explore underlying pathophysiological mechanisms that generate increased vascular permeability after burns. Many different substances have been proposed as mediators of which histamine, serotonin and oxygen radicals are claimed most important. However, no specific blocker has convincingly been shown to be clinically effective. Early work has claimed increased histamine plasma-concentrations in humans after burn and data from animal models pointed at histamine as an important mediator. Modern human clinical studies investigating the role of histamine as a mediator of the generalized post burn increase in vascular permeability are lacking.

    METHOD: We examined histamine turnover by measuring the urinary excretion of histamine and methyl histamine for 48 h after burns in 8 patients (mean total burn surface area 24%).

    RESULTS: Over time, in this time frame and compared to healthy controls we found a small increase in the excretion of histamine, but no increase of its metabolite methylhistamine.

    CONCLUSION: Our findings do not support that histamine is an important mediator of the increased systemic vascular permeability seen after burn.

  • 4.
    Johansson, Joakim
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Department of Anesthesiology and Intensive Care, Östersund Hospital, Östersund, Sweden.
    Lindahl, M.
    Gyllencreutz, E.
    Hahn, R. G.
    Symptomatic absorption of isotonic saline during transcervical endometrial resection2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 1, p. 121-124Article in journal (Refereed)
    Abstract [en]

    Absorption of irrigating fluid is a well-known complication of endoscopic surgeries, such as transurethral resection of the prostate and transcervical endometrial resection (TCER). Irrigating fluid is used to distend the hollow organ and allows the surgeon to visualize the operating field. Traditional monopolar diathermy requires irrigating fluid to be electrolyte free, which is unphysiological and therefore elicits various symptoms when absorbed.(1-4) In recent years, endoscopic resections have often been conducted with a bipolar resectoscope, which allows crystalloid fluid to be used for irrigation. The symptoms, hemodynamic effects, and biochemical changes that arise from rapid inadvertent overload of crystalloid fluid in clinical settings are not as well known as those due to overload of electrolyte-free fluid. Further, current guidelines may be interpreted as that 2500-ml resorption of saline could be accepted.(5) Therefore, we describe two patients who absorbed isotonic saline during TCERs performed under general anesthesia. The second one (case B) probably was further complicated by a venous gas embolus.

  • 5.
    Johansson, Joakim
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Department of Perioperative Medicine, Faculty of Health Sciences, Linköping University Hospital, Linköping, Sweden.
    Lindbom, Lennart
    Herwald, Heiko
    Sjöberg, Folke
    Neutrophil-derived heparin binding protein--a mediator of increased vascular permeability after burns?2009In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 35, no 8Article in journal (Refereed)
    Abstract [en]

    Increased vascular permeability and oedema formation constitute a major clinical challenge following burns. Several clinical studies show that leukocytes are systemically activated following burns. Neutrophils have the capability to increase vascular permeability via mechanisms thought to involve the release of heparin binding protein (HBP). We hypothesised that HBP is elevated in plasma after major burns due to a systemic inflammatory response and investigated plasma-HBP concentrations in 10 severely burned patients daily for 1 week following the burn. Five-fold higher levels in plasma-HBP concentration compared to a control group were detected on the first day after injury, followed by a steep reduction in the time-period that corresponds to the last part of the hyperpermeability phase. These data are in accordance with the hypothesis that HBP may function as a mediator of the early burn-induced increase in vascular permeability, and call for further studies to confirm a possible cause-and-effect relationship between HBP and oedema formation following burns.

  • 6.
    Johansson, Joakim
    et al.
    Anestesiläkaravdelningen, Östersunds sjukhus.
    Sjöberg, F
    Response to the article by Jämsä: Leukocyte receptor expression as a biomarker for severe sepsis2016In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 3, p. 407-408Article in journal (Refereed)
  • 7.
    Johansson, Joakim
    et al.
    The research and development unit, Jämtland county council; Department of Anaesthesiology and Intensive Care, Östersund Hospital, Östersund, Sweden.
    Sjöberg, Jonas
    Nordgren, Marie
    Sandström, Erik
    Sjöberg, Folke
    Zetterström, Henrik
    Prehospital analgesia using nasal administration of S-ketamine: a case series2013In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 21, article id 38Article in journal (Refereed)
    Abstract [en]

    Pain is a problem that often has to be addressed in the prehospital setting. The delivery of analgesia may sometimes prove challenging due to problems establishing intravenous access or a harsh winter environment. To solve the problem of intravenous access, intranasal administration of drugs is used in some settings. In cases where vascular access was foreseen or proved hard to establish (one or two missed attempts) on the scene of the accident we use nasally administered S-Ketamine for prehospital analgesia. Here we describe the use of nasally administered S-Ketamine in 9 cases. The doses used were in the range of 0,45-1,25 mg/kg. 8 patients were treated in outdoor winter-conditions in Sweden. 1 patient was treated indoor. VAS-score decreased from a median of 10 (interquartile range 8-10) to 3 (interquartile range 2-4). Nasally administered S-Ketamine offers a possible last resource to be used in cases where establishing vascular access is difficult or impossible. Side-effects in these 9 cases were few and non serious. Nasally administered drugs offer a needleless approach that is advantageous for the patient as well as for health personnel in especially challenging selected cases. Nasal as opposed to intravenous analgesia may reduce the time spent on the scene of the accident and most likely reduces the need to expose the patient to the environment in especially challenging cases of prehospital analgesia. Nasal administration of S-ketamine is off label and as such we only use it as a last resource and propose that the effect and safety of the treatment should be further studied.

  • 8.
    Johansson, Joakim
    et al.
    Department of Perioperative Medicine, Faculty of Health Sciences, Linköping University Hospital, Linköping, Sweden.
    Sjögren, Florence
    Bodelsson, Mikael
    Sjöberg, Folke
    Dynamics of leukocyte receptors after severe burns: an exploratory study2011In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 37, no 2, p. 227-233Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients with burns are susceptible to organ failure, and there is indirect evidence that leukocytes may contribute to this process. They may change the expression of cell-surface receptors after certain stimuli, for example, the burn. We therefore aimed to assess the changes induced by the burn in the expression of leukocyte cell-surface receptors CD11b, CD14, CD16, and CD62L on the surface of PMNs and monocytes. We also wanted to examine the dynamics of this activation during the first week after the burn, and to relate it to the size of the injury.

    METHODS: Ten patients with burns of >15% (TBSA) were included in the study. Blood samples were collected on arrival and every consecutive morning during the first week. Healthy volunteers acted as controls.

    RESULTS: PMN CD11b expression was increased. The extent of PMN CD11b expression correlated negatively to the size of the full thickness burn. Monocyte CD14 expression increased initially but there was no relation to the size of the burn. PMN CD16 expression decreased initially during the first days and the decrease was related to burn size. CD62L did not vary depending on the burn in either PMN or monocytes during the first week after the burn.

    CONCLUSION: This study showed that specific receptors on the surface of leukocytes (PMN CD11b, monocyte CD14 and PMN CD16) are affected by the burn. Expression of PMN CD11b and CD16 are related to burn size. Burn-induced effects on the expression of PMN receptors, such as PMN CD11b and CD16, may contribute to burn-induced infection susceptibility.

  • 9.
    Johansson, Joakim
    et al.
    Department of Anaesthesiology and Intensive Care, Östersund Hospital, Östersund, Sweden.
    Steinvall, Ingrid
    Herwald, Heiko
    Lindbom, Lennart
    Sjöberg, Folke
    Alteration of Leukocyte Count Correlates With Increased Pulmonary Vascular Permeability and Decreased PaO2: FiO2 Ratio Early After Major Burns.2015In: Journal of Burn Care & Research, ISSN 1559-047X, E-ISSN 1559-0488, Vol. 36, no 4, p. 484-492Article in journal (Refereed)
    Abstract [en]

    Leukocytes are activated systemically and their numbers increase soon after a burn followed by a rapid decline to low normal or subnormal levels, possibly by increased extravasation. Experimental data support that an important target for such extravasation is the lungs and that leukocytes when they adhere to endothelial cells cause an increase in vascular permeability. The authors investigated a possible relation between early increased pulmonary vascular permeability or a decreased PaO2:FiO2 ratio and the dynamic change in concentration of blood leukocytes after a burn. This is a prospective, exploratory, single-center study. The authors measured the dynamic changes of leukocytes in blood starting early after the burn, pulmonary vascular permeability index by thermodilution, and PaO2:FiO2-ratios in 20 patients during the first 21 days after a major burn (>20% TBSA%). Median TBSA was 40% interquartile range (IQR, 25-52) and full thickness burn 28% (IQR, 2-39). There was a correlation between the early (<24 hours) alteration in white blood cell count and both early increased pulmonary vascular permeability (r = .63, P = .004) and the decreased oxygenation index defined as PaO2:FiO2 < 27 kPa (P = .004). The authors have documented a correlation between dynamic change of blood leukocytes and pulmonary failure early after burns.

  • 10.
    Larsson, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Gouveia-Figueira, Sandra
    Umeå University.
    Claesson, Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Lehtipalo, Stefan
    Umeå University.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Tyden, Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Pinto, Rui
    Umeå University.
    Nording, M. L.
    Umeå University.
    Oxylipin Profiling In The Acute Respiratory Distress Syndrome2016In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 193, article id A4419Article in journal (Refereed)
  • 11. Nelson, Axel
    et al.
    Johansson, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Unit of Research, Education and Development, Östersund.
    Tydén, Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Unit of Research, Education and Development, Östersund.
    Bodelsson, Mikael
    Circulating syndecans during critical illness2017In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 125, no 5, p. 468-475Article in journal (Refereed)
    Abstract [en]

    Circulating syndecans are proposed to be markers of glycocalyx degradation and previous investigations have found higher plasma levels of syndecan-1 among patients with different pathological conditions. We wanted to investigate if levels of other syndecans (-2,-3 and -4) are altered during critical illness and compare the levels to syndecan-1. In 137 consecutive intensive care unit (ICU) patients with sepsis, cardiac arrest, gastrointestinal bleeding, intoxication or trauma, plasma levels of syndecan-1, -2, -3 and -4 were measured using ELISA. Syndecan-1 and syndecan-3 levels were similar among the different ICU patient groups but higher than controls. No differences in plasma levels of syndecan-2 or syndecan-4 were found neither among the different ICU patient groups nor compared to controls. All syndecans showed an association with mortality and the levels of syndecan-1 and -3 and correlated with each other. The results indicate that syndecan release is triggered by the physiological stress of critical illness in general and involves several subtypes such as syndecan-1 and syndecan-3.

  • 12.
    Samuelsson, Line
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Tyden, Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Herwald, Heiko
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Walldén, Jakob
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Steinvall, Ingrid
    Sjöberg, Folke
    Johansson, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Renal clearance of heparin-binding protein and elimination during renal replacement therapy: Studies in ICU patients and healthy volunteers2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 8, article id e0221813Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Heparin-binding protein (HBP) is released by neutrophils upon activation, and elevated plasma levels are seen in inflammatory states like sepsis, shock, cardiac arrest, and burns. However, little is known about the elimination of HBP. We wanted to study renal clearance of HBP in healthy individuals and in burn patients in intensive care units (ICUs). We also wished to examine the levels of HBP in the effluent of renal replacement circuits in ICU patients undergoing continuous renal replacement therapy (CRRT).

    METHODS: We measured plasma and urine levels of HBP and urine flow rate in 8 healthy individuals and 20 patients in a burn ICU. In 32 patients on CRRT, we measured levels of HBP in plasma and in the effluent of the CRRT circuit.

    RESULTS: Renal clearance of HBP (median (IQR) ml/min) was 0.19 (0.08-0.33) in healthy individuals and 0.30 (0.01-1.04) in burn ICU patients. In ICU patients with cystatin C levels exceeding 1.44 mg/l, clearance was 0.45 (0.15-2.81), and in patients with cystatin C below 1.44 mg/l clearance was lower 0.28 (0.14-0.55) (p = 0.04). Starting CRRT did not significantly alter plasma levels of HBP (p = 0.14), and the median HBP level in the effluent on CRRT was 9.1 ng/ml (IQR 7.8-14.4 ng/ml).

    CONCLUSION: In healthy individuals and critically ill burn patients, renal clearance of HBP is low. It is increased when renal function is impaired. Starting CRRT in critically ill patients does not alter plasma levels of HBP significantly, but HBP can be found in the effluent. It seems unlikely that impaired kidney function needs to be considered when interpreting concentrations of HBP in previous studies. Starting CRRT does not appear to be an effective way of reducing HBP concentrations.

  • 13.
    Schollin-Borg, Maria
    et al.
    Department of Anesthesiology and Intensive Care, Östersund Hospital, 83183 Östersund, Sweden.
    Nordin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Zetterström, Henrik
    Department of Surgical Sciences, Anesthesiology and Critical Care Medicine, Uppsala University, 75185 Uppsala, Sweden.
    Johansson, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Department of Anesthesiology and Intensive Care, Östersund Hospital, 83183 Östersund, Sweden.
    Blood Lactate Is a Useful Indicator for the Medical Emergency Team2016In: Critical Care Research and Practice, ISSN 2090-1305, E-ISSN 2090-1313, article id 5765202Article in journal (Refereed)
    Abstract [en]

    Lactate has been thoroughly studied and found useful for stratification of patients with sepsis, in the Intensive Care Unit, and trauma care. However, little is known about lactate as a risk-stratification marker in the Medical Emergency Team-(MET-) call setting. We aimed to determine whether the arterial blood lactate level at the time of a MET-call is associated with increased 30-day mortality. This is an observational study on a prospectively gathered cohort at a regional secondary referral hospital. All MET-calls during the two-year study period were eligible. Beside blood lactate, age and vital signs were registered at the call. Among the 211 calls included, there were 64 deaths (30.3%). Median lactate concentration at the time of the MET-call was 1.82 mmol/L (IQR 1.16-2.7). We found differences between survivors and nonsurvivors for lactate and oxygen saturation, a trend for age, but no significant correlations between mortality and systolic blood pressure, respiratory rate, and heart rate. As compared to normal lactate (<2.44 mmol/L), OR for 30-day mortality was 3.54 (p < 0.0006) for lactate 2.44-5.0 mmol/L and 4.45 (p < 0.0016) for lactate >5.0 mmol/L. The present results support that immediate measurement of blood lactate in MET call patients is a useful tool in the judgment of illness severity.

  • 14.
    Tydén, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Herwald, H.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Walldén, Jakob
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Heparin-binding protein as a biomarker of acute kidney injury in critical illness2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 7, p. 797-803Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is no biomarker with high sensitivity and specificity for the development of acute kidney injury (AKI) in a mixed intensive care unit (ICU) population. Heparin-binding protein (HBP) is released from granulocytes and causes increased vascular permeability which plays a role in the development of AKI in sepsis and ischemia. The aim of this study was to investigate whether plasma levels of HBP on admission can predict the development of AKI in a mixed ICU population and in the subgroup with sepsis. METHODS: Longitudinal observational study with plasma HBP levels from 245 patients taken on admission to ICU. Presence and severity of AKI was scored daily for 1 week. RESULTS: Mean (95% CI) plasma concentrations of log HBP (ng/ml) in the groups developing different stages of AKI were: stage 0 (n = 175), 3.5 (3.4-3.7); stage 1 (n = 33), 3.7 (3.5-4.0), stage 2 (n = 20), 4.4 (3.5-4.8); and stage 3 (n = 17), 4.6 (3.8-5.2). HBP levels were significantly higher in patients developing AKI stage 3 (P < 0.01) compared to AKI stage 0 and 1. The area under the curve (AUC) for HBP to discriminate the group developing AKI stage 2-3 was 0.70 (CI: 0.58-0.82) and in the subgroup with severe sepsis 0.88 (CI: 0.77-0.99). CONCLUSION: Heparin-binding protein levels on admission to ICU are associated with the development of severe kidney injury. The relationship between HBP and AKI needs to be further validated in larger studies.

  • 15.
    Tydén, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Department of Anaesthesiology and Intensive Care, Östersund Hospital, Östersund, Sweden.
    Herwald, Heiko
    Sjoberg, Folke
    Johansson, Joakim
    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.
    Increased Plasma Levels of Heparin-Binding Protein on Admission to Intensive Care Are Associated with Respiratory and Circulatory Failure2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, article id e0152035Article in journal (Refereed)
    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.

  • 16.
    Tydén, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiläkaravdelningen, Östersund Hospital, Östersund, Sweden.
    Larsson, Niklas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Lehtipalo, Stefan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Herwald, H
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Walldén, Jakob
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Heparin-binding protein in ventilator-induced lung injury.2018In: Intensive Care Medicine Experimental, ISSN 1646-2335, E-ISSN 2197-425X, Vol. 6, no 1, article id 33Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although mechanical ventilation is often lifesaving, it can also cause injury to the lungs. The lung injury is caused by not only high pressure and mechanical forces but also by inflammatory processes that are not fully understood. Heparin-binding protein (HBP), released by activated granulocytes, has been indicated as a possible mediator of increased vascular permeability in the lung injury associated with trauma and sepsis. We investigated if HBP levels were increased in the bronchoalveolar lavage fluid (BALF) or plasma in a pig model of ventilator-induced lung injury (VILI). We also investigated if HBP was present in BALF from healthy volunteers and in intubated patients in the intensive care unit (ICU).

    METHODS: Anaesthetized pigs were randomized to receive ventilation with either tidal volumes of 8 ml/kg (controls, n = 6) or 20 ml/kg (VILI group, n = 6). Plasma and BALF samples were taken at 0, 1, 2, 4, and 6 h. In humans, HBP levels in BALF were sampled from 16 healthy volunteers and from 10 intubated patients being cared for in the ICU.

    RESULTS: Plasma levels of HBP did not differ between pigs in the control and VILI groups. The median HBP levels in BALF were higher in the VILI group after 6 h of ventilation compared to those in the controls (1144 ng/ml (IQR 359-1636 ng/ml) versus 89 ng/ml (IQR 33-191 ng/ml) ng/ml, respectively, p = 0.02). The median HBP level in BALF from healthy volunteers was 0.90 ng/ml (IQR 0.79-1.01 ng/ml) as compared to 1959 ng/ml (IQR 612-3306 ng/ml) from intubated ICU patients (p < 0.001).

    CONCLUSIONS: In a model of VILI in pigs, levels of HBP in BALF increased over time compared to controls, while plasma levels did not differ between the two groups. HBP in BALF was high in intubated ICU patients in spite of the seemingly non-harmful ventilation, suggesting that inflammation from other causes might increase HBP levels.

  • 17.
    Werr, J
    et al.
    Department of Physiology and .
    Johansson, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Eriksson, E E
    Hedqvist, P
    Ruoslahti, E
    Lindbom, L
    Integrin alpha(2)beta(1) (VLA-2) is a principal receptor used by neutrophils for locomotion in extravascular tissue.2000In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 95, no 5Article in journal (Refereed)
    Abstract [en]

    Cell adhesion molecules are critically involved in the multistep process of leukocyte recruitment in inflammation. The specific receptors used by polymorphonuclear leukocytes (PMN) for locomotion in extravascular tissue have as yet not been identified. By means of immunofluorescence flow cytometry and laser scanning confocal microscopy, this study demonstrated that surface expression of the alpha(2)beta(1) (VLA-2) integrin, though absent on blood PMN, is induced in extravasated PMN collected from human skin blister chambers, and rat PMN accumulated in the peritoneal cavity after chemotactic stimulation. Intravital time-lapse videomicroscopy was used to investigate chemoattractant-induced PMN locomotion in the rat mesentery in vivo. Local administration of function-blocking monoclonal antibody or peptide recognizing the alpha(2)beta(1) integrin reduced PMN migration velocity in the extravascular tissue by 73% +/- 3% and 70% +/- 10%, respectively (means +/- SD). The distance f-met-leu-phe peptide (fMLP)-stimulated human PMN migrated in a collagen gel in vitro was markedly reduced by treatment with anti-alpha(2) mAbs or peptide, whereas no effect was observed with antibodies or peptides recognizing the alpha(4)beta(1) or alpha(5)beta(1) integrins. Further evidence for a critical role of expression of alpha(2)beta(1) integrin in PMN locomotion in extravascular tissue was obtained in the mouse air pouch model of acute inflammation where chemoattractant-induced PMN recruitment was substantially inhibited by local anti-alpha(2) mAb treatment. Thus, expression of alpha(2)beta(1) integrin on extravasated PMN has been identified and a novel role of this receptor in regulating the extravascular phase of leukocyte trafficking in inflammation has been formulated. (Blood. 2000;95:1804-1809)

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