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  • 51.
    Otterbeck, Alexander
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hanslin, Katja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lantz, E. Lidberg
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Stålberg, J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Inhalation of specific anti-Pseudomonas aeruginosa IgY antibodies transiently decreases P. aeruginosa colonization of the airway in mechanically ventilated piglets2019Ingår i: Intensive Care Medicine Experimental, ISSN 1646-2335, E-ISSN 2197-425X, Vol. 7, artikel-id 21Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: P. aeruginosa is a pathogen frequently resistant to antibiotics and a common cause of ventilator-associated pneumonia (VAP). Non-antibiotic strategies to prevent or treat VAP are therefore of major interest. Specific polyclonal avian IgY antibodies have previously been shown to be effective against pneumonia caused by P. aeruginosa in rodents and against P. aeruginosa airway colonization in patients. Objectives: To study the effect of specific polyclonal anti-P. aeruginosa IgY antibodies (Pa-IgY) on colonization of the airways in a porcine model. Method: The pigs were anesthetized, mechanically ventilated, and subject to invasive hemodynamic monitoring and allocated to either receive 10(9) CFU nebulized P. aeruginosa (control, n=6) or 10(9) CFU nebulized P. aeruginosa + 200 mg Pa-IgY antibodies (intervention, n=6). Physiological measurement, blood samples, and tracheal cultures were then secured regularly for 27 h, after which the pigs were sacrificed and lung biopsies were cultured. Results: After nebulization, tracheal growth of P. aeruginosa increased in both groups during the experiment, but with lower growth in the Pa-IgY-treated group during the experiment (p = 0.02). Tracheal growth was 4.6 x 10(3) (9.1 x 10(2)-3.1 x 10(4)) vs. 4.8 x 10(4) (7.5 x 10(3)-1.4 x 10(5)) CFU/mL in the intervention group vs. the control group at 1h and 5.0 x 10(0) (0.0 x 10(0)-3.8 x 10(2)) vs. 3.3 x 10(4) (8.0 x 10(3)-1.4 x 10(5)) CFU/mL at 12 h in the same groups. During this time, growth in the intervention vs. control group was one to two orders of ten lower. After 12 h, the treatment effect disappeared and bacterial growth increased in both groups. The intervention group had lower body temperature and cardiac index and higher static compliance compared to the control group. Conclusion: In this porcine model, Pa-IgY antibodies lessen bacterial colonization of the airways.

  • 52.
    Otterbeck, Alexander
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hanslin, Katja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lidberg Lantz, Elin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Stålberg, J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Correction to: Inhalation of specific anti-Pseudomonas aeruginosa IgY antibodies transiently decreases P. aeruginosa colonization of the airway in mechanically ventilated piglets.2019Ingår i: Intensive Care Medicine Experimental, ISSN 1646-2335, E-ISSN 2197-425X, Vol. 7, artikel-id 24Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Following publication of the original article, the authors flagged that an incorrect piece of data is given in the Materials and Methods section of the article.

  • 53. Schneider, Antoine G
    et al.
    Eastwood, Glenn M
    Bellomo, Rinaldo
    Bailey, Michael
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Pilcher, David
    Young, Paul
    Stow, Peter
    Santamaria, John
    Stachowski, Edward
    Suzuki, Satoshi
    Woinarski, Nicholas C
    Pilcher, Janine
    Arterial carbon dioxide tension and outcome in patients admitted to the intensive care unit after cardiac arrest2013Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 84, nr 7, s. 927-934Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Arterial carbon dioxide tension (PaCO2) affects neuronal function and cerebral blood flow. However, its association with outcome in patients admitted to intensive care unit (ICU) after cardiac arrest (CA) has not been evaluated.

    Methods and results

    Observational cohort study using data from the Australian New Zealand (ANZ) Intensive Care Society Adult-Patient-Database (ANZICS-APD). Outcomes analyses were adjusted for illness severity, co-morbidities, hypothermia, treatment limitations, age, year of admission, glucose, source of admission, PaO2 and propensity score.

    We studied 16,542 consecutive patients admitted to 125 ANZ ICUs after CA between 2000 and 2011. Using the APD-PaCO2 (obtained within 24 h of ICU admission), 3010 (18.2%) were classified into the hypo- (PaCO2 < 35 mmHg), 6705 (40.5%) into the normo- (35–45 mmHg) and 6827 (41.3%) into the hypercapnia (>45 mmHg) group. The hypocapnia group, compared with the normocapnia group, had a trend toward higher in-hospital mortality (OR 1.12 [95% CI 1.00–1.24, p = 0.04]), lower rate of discharge home (OR 0.81 [0.70–0.94, p < 0.01]) and higher likelihood of fulfilling composite adverse outcome of death and no discharge home (OR 1.23 [1.10–1.37, p < 0.001]). In contrast, the hypercapnia group had similar in-hospital mortality (OR 1.06 [0.97–1.15, p = 0.19]) but higher rate of discharge home among survivors (OR 1.16 [1.03–1.32, p = 0.01]) and similar likelihood of fulfilling the composite outcome (OR 0.97 [0.89–1.06, p = 0.52]). Cox-proportional hazards modelling supported these findings.

    Conclusions

    Hypo- and hypercapnia are common after ICU admission post-CA. Compared with normocapnia, hypocapnia was independently associated with worse clinical outcomes and hypercapnia a greater likelihood of discharge home among survivors.

  • 54. Schneider, Antoine G.
    et al.
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Bailey, Michael
    Pilcher, David V.
    Bellomo, Rinaldo
    Relationship between illness severity scores in acute kidney injury2012Ingår i: Critical care and resuscitation, ISSN 1441-2772, Vol. 14, nr 1, s. 53-55Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In the field of critical care nephrology, recent publications have used different illness severity scoring systems, making outcome comparisons difficult.

    Objective: To establish a methodology to translate one illness severity scoring system into another for critically ill patients with acute kidney injury (AKI). Design: Statistical analysis of prospectively obtained data.

    Methods: Using data from the Australian and New Zealand Intensive Care Society Adult Patient Database, we obtained Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III and Simplified Acute Physiology Score (SAPS II) scores for all patients admitted with AKI. We applied correlation and linear regression analyses as well as cross-validation with holdout samples.

    Results: Between 2001 and 2010, the three illness severity scores were obtained in 636 431 admissions. Of these, 37 203 fulfilled the APACHE score criteria for AKI. The coefficient of determination (R-2) between APACHE II and APACHE III scores was 0.66. The overall model was APACHE III = 3.13 x APACHE II + 7.99 (P<0.001). Similarly, the R-2 between APACHE III and the SAPS II scores was 0.78. The overall model was APACHE III = 1.49 x SAPS II + 15.5 (P<0.001). The R-2 between APACHE II and SAPS II scores was 0.62. The overall model was APACHE II = 0.35 x SAPS II + 9.3 (P<0.001).

    Conclusions: Simple, robust translational formulae can be developed to allow clinicians to compare illness severity of patients with AKI when illness severity is expressed with different scoring systems.

  • 55. Schneider, Antoine G
    et al.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Bailey, Michael
    Pilcher, David V
    Bellomo, Rinaldo
    Simple translational equations to compare illness severity scores in intensive care trials2013Ingår i: Journal of critical care, ISSN 0883-9441, E-ISSN 1557-8615, Vol. 28, nr 5, s. 885.e1-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE:

    Comparison of illness severity for intensive care unit populations assessed according to different scoring systems should increase our ability to compare and meta-analyze past and future trials but is currently not possible. Accordingly, we aimed to establish a methodology to translate illness severity scores obtained from one system into another.

    MATERIALS AND METHODS:

    Using the Australian and New-Zealand intensive care adult patient database, we obtained simultaneous admission Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III scores and Simplified Acute Physiology Score (SAPS) II in 634428 patients admitted to 153 units between 2001 and 2010. We applied linear regression analyses to create models enabling translation of one score into another. Sensitivity analyses were performed after removal of diagnostic categories excluded from the original APACHE database, after matching for similar risk of death, after splitting data according to country of origin (Australia or New Zealand) and after splitting admissions occurring before or after 2006.

    RESULTS:

    The translational models were APACHE III = 3.08 × APACHE II + 5.75; APACHE III = 1.47 × SAPS II + 8.6; and APACHE II = 0.36 × SAPS II + 4.4. The area under the receiver operating curve for mortality prediction was 0.853 (95% confidence interval, 0.851-0.855) for the "APACHE II derived APACHE III" score and 0.854 (0.852-0.855) for the "SAPS II derived APACHE III" vs 0.854 (0.852-0.855) for the original APACHE III score. Similarly, it was 0.841 (0.839-0.843) for the "SAPS II derived APACHE II score" vs 0.842 (0.840-0.843) for the original APACHE II score. Correlation coefficients as well as intercepts remained very similar in all subgroups analyses.

    CONCLUSIONS:

    Simple and robust translational formulas can be developed to allow clinicians to compare illness severity between studies involving critically ill patients. Further studies in other countries and health care systems are needed to confirm the generalizability of these results.

  • 56.
    Simm, Mikael
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Söderberg, Ewa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Castegren, Markus
    Department of Anaesthesia, Intensive Care & Surgical Services, Karolinska University Hospital, Huddinge, Stockholm, Sweden..
    Nilsen, Tom
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Performance of plasma calprotectin as a biomarker of early sepsis: a pilot study2016Ingår i: Biomarkers in Medicine, ISSN 1752-0363, E-ISSN 1752-0371, Vol. 10, nr 8, s. 811-818Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: To determine the performance of plasma calprotectin as a marker of sepsis on intensive care unit (ICU) admission and as a marker of mortality day 30 post-ICU admission.

    MATERIALS & METHODS: Consecutive ICU patients were allocated to: sepsis (n = 15), postoperative inflammation (n = 23) and intoxication without inflammation (n = 7) groups.

    RESULTS: Calprotectin was 4.3 (2.6-8.2; mg/l; median [interquartile range]) in the sepsis, 2.8 (1.6-4.4) in the postoperative and 0.7 (0.4-1.6) in the intoxication groups. Area under the receiver operating characteristic curve for sepsis versus intoxication group was: 0.95, for sepsis versus postoperative groups: 0.65 and for survivors versus nonsurvivors: 0.70.

    CONCLUSION: Calprotectin was a sensitive marker of systemic inflammation, is a potential sepsis marker and performed well as mortality predictor in this pilot study.

  • 57.
    Skorup, Paul
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Maudsdotter, Lisa
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Jonsson, Ann-Beth
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Beneficial Antimicrobial Effect of the Addition of an Aminoglycoside to a β-Lactam Antibiotic in an E. coli Porcine Intensive Care Severe Sepsis Model.2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 2, s. e90441-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study aimed to determine whether the addition of an aminoglycoside to a ß-lactam antibiotic increases the antimicrobial effect during the early phase of Gram-negative severe sepsis/septic shock. A porcine model was selected that considered each animal's individual blood bactericidal capacity. Escherichia coli, susceptible to both antibiotics, was given to healthy pigs intravenously during 3 h. At 2 h, the animals were randomized to a 20-min infusion with either cefuroxime alone (n = 9), a combination of cefuroxime+tobramycin (n = 9), or saline (control, n = 9). Blood samples were collected hourly for cultures and quantitative polymerase chain reaction (PCR). Bacterial growth in the organs after 6 h was chosen as the primary endpoint. A blood sample was obtained at baseline before start of bacterial infusion for ex vivo investigation of the blood bactericidal capacity. At 1 h after the administration of the antibiotics, a second blood sample was taken for ex vivo investigation of the antibiotic-induced blood killing activity. All animals developed severe sepsis/septic shock. Blood cultures and PCR rapidly became negative after completed bacterial infusion. Antibiotic-induced blood killing activity was significantly greater in the combination group than in the cefuroxime group (p<0.001). Growth of bacteria in the spleen was reduced in the two antibiotic groups compared with the controls (p<0.01); no difference was noted between the two antibiotic groups. Bacterial growth in the liver was significantly less in the combination group than in the cefuroxime group (p<0.05). High blood bactericidal capacity at baseline was associated with decreased growth in the blood and spleen (p<0.05). The addition of tobramycin to cefuroxime results in increased antibiotic-induced blood killing activity and less bacteria in the liver than cefuroxime alone. Individual blood bactericidal capacity may have a significant effect on antimicrobial outcome.

  • 58.
    Skorup, Paul
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Maudsdotter, Lisa
    Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Mode of Bacterial Killing Affects the Inflammatory Response and Associated Organ Dysfunctions in a Porcine E. coli Intensive Care Sepsis ModelManuskript (preprint) (Övrigt vetenskapligt)
  • 59.
    Skorup, Paul
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Maudsdotter, Lisa
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden.
    Tano, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Castegren, Markus
    Perioperative Medicine and Intensive Care (PMI) and CLINTEC, Karolinska Institute, Stockholm, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Dynamics of Endotoxin, Inflammatory Variables, and Organ Dysfunction After Treatment With Antibiotics in an Escherichia coli Porcine Intensive Care Sepsis Model2018Ingår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 46, nr 7, s. e634-e641Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To investigate the dynamics of antibiotic-induced endotoxin liberation and inflammatory response in vivo in a clinically relevant large animal intensive care sepsis model and whether the addition of an aminoglycoside to a β-lactam antibiotic affects these responses.

    DESIGN: Prospective, placebo-controlled interventional experimental study.

    SETTING: University research unit.

    SUBJECTS: Thirty-six healthy pigs administered Escherichia coli as a 3-hour infusion.

    INTERVENTIONS: After 2 hours, during E. coli infusion, the animals were exposed to cefuroxime alone, the combination of cefuroxime and tobramycin, or saline.

    MEASUREMENTS AND MAIN RESULTS: Plasma endotoxin, interleukin-6, tumor necrosis factor-α, leucocytes, and organ dysfunction were recorded for 4 hours after antibiotic treatment, and differences to the values before treatment were calculated. In vitro experiments were performed to ascertain whether endotoxin is released during antibiotic-induced bacterial killing of this E. coli strain. Despite differences between the treatment arms in vitro, no differences in plasma endotoxin were observed in vivo. Antibiotic-treated animals demonstrated a higher interleukin-6 response (p < 0.001), greater leucocyte activation (p < 0.001), and more pronounced deterioration in pulmonary static compliance (p < 0.01) over time than controls. Animals treated with the combination showed a trend toward less inflammation.

    CONCLUSIONS: Treatment with antibiotics may elicit an increased inflammatory interleukin-6 response that is associated with leucocyte activation and pulmonary organ dysfunction. No observable differences were detected in plasma endotoxin concentrations. The reduction in cefuroxime-induced endotoxin release after the addition of an aminoglycoside in vitro could not be reproduced in this model.

  • 60.
    Skorup, Paul
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Wilske, Frida
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Hanslin, Katja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Enhanced Bacterial Clearance at a Secondary Sepsis Challenge in an Endotoxin-tolerant Porcine Intensive Care ModelManuskript (preprint) (Övrigt vetenskapligt)
  • 61.
    Sperber, Jesper
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Evaluating the effects of protective ventilation on organ-specific cytokine production in porcine experimental postoperative sepsis2015Ingår i: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 15, artikel-id 60Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Protective ventilation with lower tidal volume (VT) and higher positive end-expiratory pressure (PEEP) reduces the negative additive effects of mechanical ventilation during systemic inflammatory response syndrome. We hypothesised that protective ventilation during surgery would affect the organ-specific immune response in an experimental animal model of endotoxin-induced sepsis-like syndrome.

    METHODS: 30 pigs were laparotomised for 2 hours (h), after which a continuous endotoxin infusion was started at 0.25 micrograms × kg(-1) × h(-1) for 5 h. Catheters were placed in the carotid artery, hepatic vein, portal vein and jugular bulb. Animals were randomised to two protective ventilation groups (n = 10 each): one group was ventilated with VT 6 mL × kg(-1) during the whole experiment while the other group was ventilated during the surgical phase with VT of 10 mL × kg(-1). In both groups PEEP was 5 cmH2O during surgery and increased to 10 cmH2O at the start of endotoxin infusion. A control group (n = 10) was ventilated with VT of 10 mL × kg(-1) and PEEP 5 cm H20 throughout the experiment. In four sample locations we a) simultaneously compared cytokine levels, b) studied the effect of protective ventilation initiated before and during endotoxemia and c) evaluated protective ventilation on organ-specific cytokine levels.

    RESULTS: TNF-alpha levels were highest in the hepatic vein, IL-6 levels highest in the artery and jugular bulb and IL-10 levels lowest in the artery. Protective ventilation initiated before and during endotoxemia did not differ in organ-specific cytokine levels. Protective ventilation led to lower levels of TNF-alpha in the hepatic vein compared with the control group, whereas no significant differences were seen in the artery, portal vein or jugular bulb.

    CONCLUSIONS: Variation between organs in cytokine output was observed during experimental sepsis. We see no implication from cytokine levels for initiating protective ventilation before endotoxemia. However, during endotoxemia protective ventilation attenuates hepatic inflammatory cytokine output contributing to a reduced total inflammatory burden.

  • 62.
    Sperber, Jesper
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lung protective ventilation induces immunotolerance and nitric oxide metabolites in porcine experimental postoperative sepsis2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 12, s. e83182-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Low tidal volume ventilation is beneficial in patients with severe pulmonary dysfunction and would, in theory, reduce postoperative complications if implemented during routine surgery. The study aimed to investigate whether low tidal volume ventilation and high positive end-expiratory pressure (PEEP) in a large animal model of postoperative sepsis would attenuate the systemic inflammatory response and organ dysfunction. Thirty healthy pigs were randomized to three groups: Group Prot-7h, i.e. protective ventilation for 7 h, was ventilated with a tidal volume of 6 mL x kg-1 for 7 h; group Prot-5h, i.e. protective ventilation for 5 h, was ventilated with a tidal volume of 10 mL x kg-1 for 2 h, after which the group was ventilated with a tidal volume of 6 mL x kg-1; and a control group that was ventilated with a tidal volume of 10 mL x kg-1 for 7 h. In groups Prot-7h and Prot-5h PEEP was 5 cmH2O for 2 h and 10 cmH2O for 5 h. In the control group PEEP was 5 cmH2O for the entire experiment. After surgery for 2 h, postoperative sepsis was simulated with an endotoxin infusion for 5 h. Low tidal volume ventilation combined with higher PEEP led to lower levels of interleukin 6 and 10 in plasma, higher PaO2/FiO2, better preserved functional residual capacity and lower plasma troponin I as compared with animals ventilated with a medium high tidal volume and lower PEEP. The beneficial effects of protective ventilation were seen despite greater reductions in cardiac index and oxygen delivery index. In the immediate postoperative phase low VT ventilation with higher PEEP was associated with reduced ex vivo plasma capacity to produce TNF-α upon endotoxin stimulation and higher nitrite levels in urine. These findings might represent mechanistic explanations for the attenuation of systemic inflammation and inflammatory-induced organ dysfunction.

  • 63.
    Sperber, Jesper
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Nyberg, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Exposure to Mechanical Ventilation and Endotoxin for 24 Hours Before Infection Influences Pseudomonas Aeruginosa Growth During Experimental Porcine Ventilator-Associated PneumoniaManuskript (preprint) (Övrigt vetenskapligt)
  • 64.
    Sperber, Jesper
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Nyberg, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Melhus, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi och infektionsmedicin.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Protective Ventilation Reduces Pseudomonas Aeruginosa Growth in a Porcine Pneumonia ModelManuskript (preprint) (Övrigt vetenskapligt)
  • 65.
    Sperber, Jesper
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Centre for Clinical Research Sörmland, Department of Anesthesiology & Intensive Care Mälarsjukhuset, SE-631 88 Eskilstuna, Sweden.
    Nyberg, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Centre for Clinical Research Sörmland, Department of Anesthesiology & Intensive Care Mälarsjukhuset, SE-631 88 Eskilstuna, Sweden.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Melhus, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Perioperative Medicine and Intensive Care, Karolinska University Hospital and CLINTEC, Karolinska Institute, Stockholm, Sweden.
    Protective ventilation reduces Pseudomonas aeruginosa growth in lung tissue in a porcine pneumonia model2017Ingår i: Intensive & Critical Care Nursing, ISSN 0964-3397, E-ISSN 1532-4036, Vol. 5, artikel-id 40Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Mechanical ventilation with positive end expiratory pressure and low tidal volume, i.e. protective ventilation, is recommended in patients with acute respiratory distress syndrome. However, the effect of protective ventilation on bacterial growth during early pneumonia in non-injured lungs is not extensively studied. The main objectives were to compare two different ventilator settings on Pseudomonas aeruginosa growth in lung tissue and the development of lung injury.

    METHODS: A porcine model of severe pneumonia was used. The protective group (n = 10) had an end expiratory pressure of 10 cm H2O and a tidal volume of 6 ml x kg-1. The control group (n = 10) had an end expiratory pressure of 5 cm H2O and a tidal volume of 10 ml x kg-1. 1011 colony forming units of Pseudomonas aeruginosa were inoculated intra-tracheally at baseline, after which the experiment continued for 6 h. Two animals from each group received only saline, and served as sham animals. Lung tissue samples from each animal were used for bacterial cultures and wet-to-dry weight ratio measurements.

    RESULTS: The protective group displayed lower numbers of Pseudomonas aeruginosa (p < 0.05) in the lung tissue, and a lower wet-to-dry ratio (p < 0.01) than the control group. The control group deteriorated in arterial oxygen tension/inspired oxygen fraction, whereas the protective group was unchanged (p < 0.01).

    CONCLUSIONS: In early phase pneumonia, protective ventilation with lower tidal volume and higher end expiratory pressure has the potential to reduce the pulmonary bacterial burden and the development of lung injury.

  • 66.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Gustafsson, Mats G
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Analysis of intraosseous samples using point of care technology: an experimental study in the anaesthetised pig2012Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 83, nr 11, s. 1381-1385Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Intraosseous access is an essential method in emergency medicine when other forms of vascular access are unavailable and there is an urgent need for fluid or drug therapy. A number of publications have discussed the suitability of using intraosseous access for laboratory testing. We aimed to further evaluate this issue and to study the accuracy and precision of intraosseous measurements.

    METHODS:

    Five healthy, anaesthetised pigs were instrumented with bilateral tibial intraosseous cannulae and an arterial catheter. Samples were collected hourly for 6h and analysed for blood gases, acid base status, haemoglobin and electrolytes using an I-Stat(®) point of care analyser.

    RESULTS:

    There was no clinically relevant difference between results from left and right intraosseous sites. The variability of the intraosseous sample values, measured as the coefficient of variance (CV), was maximally 11%, and smaller than for the arterial sample values for all variables except SO(2). For most variables, there seems to be some degree of systematic difference between intraosseous and arterial results. However, the direction of this difference seems to be predictable.

    CONCLUSION:

    Based on our findings in this animal model, cartridge based point of care instruments appear suitable for the analysis of intraosseous samples. The agreement between intraosseous and arterial analysis seems to be good enough for the method to be clinically useful. The precision, quantified in terms of CV, is at least as good for intraosseous as for arterial analysis. There is no clinically important difference between samples from left and right tibia, indicating a good reproducibility.

  • 67.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Intraosseous Samples Can Be Used for CreatinineMeasurements - An Experimental Study in the Anaesthetised Pig2014Ingår i: Clinical Laboratory, ISSN 1433-6510, Vol. 60, nr 10, s. 1587-1591Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Intraosseous (IO) access is a valuable tool in prehospital locations and in emergency departments when other forms of vascular access are unavailable. Creatinine is often used for dose adjustment of drugs that may be administered through intraosseous cannulae. We aimed to study the possibility of analysing creatinine in intraosseous samples and study the accuracy and precision of such measurements.

    Methods: Eight pigs with endotoxin induced septic shock were sampled hourly for six hours and analysed for plasma creatinine. Samples were collected from arterial, venous, and IO cannulae.

    Results: There was an increase in creatinine values during the later part of the experiment. The coefficients of variation between the three sampling sites were less than 10% at all sampling times.

    Conclusions: Based on our findings intraosseous samples can be used for creatinine determination in emergency settings.

  • 68.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Analysis of intraosseous samples in endotoxemic shock: an experimental study in the anaesthetised pig2014Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, nr 3, s. 337-344Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Intraosseous (IO) access is used in emergency situations to allow rapid initiation of treatment. IO access is also sometimes used for blood sampling, although data on accuracy of such sampling in critical illness are limited. There is also a potential risk that bone marrow fragments in IO samples may damage laboratory equipment. It is ethically questionable to perform a simultaneous comparison between IO and arterial/venous sampling in critically ill humans. We have, thus, studied the analytical performance of IO sampling in a porcine septic shock model using a cartridge-based analyser.

    Methods

    Eight pigs with endotoxin-induced septic shock were sampled hourly for 6 h, and analysed for blood gases, acid base status, haemoglobin, glucose and lactate using point of care instruments. Samples were taken from three IO cannulae (tibia bilaterally, one with infusion, and humerus), one arterial and one venous. An interaction test was used to assess changes in agreement between methods over time. Bland–Altman plots were constructed to study bias between methods.

    Results

    There were, to a varying extent, differences between IO and arterial/venous levels for all studied variables, but agreement did not change significantly during the experiment. A general finding was a large dispersion of differences between methods.

    Conclusions

    IO sample values should be treated with caution in this setting but may add useful information to the clinical picture. The tibia or humerus may be used for sampling. IO infusion decreases agreement, thus sampling during infusion should be avoided.

  • 69.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Intraosseous blood aspirates analysed by a portable cartridge-based device2011Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 15, nr Suppl 1, s. 49-49Artikel i tidskrift (Refereegranskat)
  • 70.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Michalek, J
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Intraosseous and intravenous administration of antibiotics yields comparable plasma concentrations during experimental septic shock2015Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, nr 3, s. 346-353Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: We aimed to investigate whether comparable antibiotic concentrations could be reached with intraosseous and intravenous administration during septic shock.

    METHODS: In this randomized, prospective experimental study conducted at an animal research laboratory at the University Hospital of Uppsala, eight anesthetized pigs, weighing 21.2 to 29.1 kg (mean: 25.2 ± 2.3 kg), received endotoxin infusion at 4 μg/kg/h for 6 h. At the onset of clinical shock, alternatively after 3 h of endotoxemia, they received 75 mg/kg of cefotaxime and 7 mg/kg of gentamicin either in a proximal tibial intraosseous catheter or in a peripheral intravenous catheter. Mixed venous samples were taken after 5, 15, 30, 60, 120 and 180 min and analyzed for antibiotic concentrations.

    RESULTS: For both antibiotics, plasma concentrations after intraosseous and intravenous administration followed similar curves throughout the observation period, and peak concentrations were comparable. Mean concentration area under the curve (AUC mg × h/l) for cefotaxime was 108.1 ± 19.5 after intraosseous and 116.5 ± 11.1 after intravenous administration; ratio 0.93, (95% CI 0.71-1.19). Mean AUC for gentamicin was 28.1 ± 6.8 for intraosseous and 32.2 ± 3.5 for intravenous administration; ratio 0.87 (95% CI 0.62-1.19).

    CONCLUSIONS: In this porcine septic shock model, intraosseous and intravenous administration of gentamicin and cefotaxime yielded comparable concentrations. In an emergency, intraosseous administration of these antibiotics may be considered in severe infections when venous access is difficult.

  • 71.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Comparison of Intraosseous, Arterial, and Venous Blood Sampling for Laboratory Analysis in Hemorrhagic Shock2019Ingår i: Clinical Laboratory, ISSN 1433-6510, Vol. 65, nr 7, s. 1169-1177Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Intraosseous (IO) access is often indicated for administration of drugs and fluids in emergencies when venous access is challenging. There is no consensus regarding whether and which laboratory analyses may be performed on IO aspirates, and research on hemodynamically unstable subjects is limited.

    Methods: Twelve anesthetized pigs were sampled from IO, venous, and arterial accesses during stable circulation and after hemorrhage corresponding to 20% and 40% of the blood volume. Samples were analyzed for blood gases and acid-base status, electrolytes, hematocrit, creatinine, glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), alkaline phosphatase (ALP), and creatine kinase (CK).

    Results: Average differences of blood gases and acid-base parameters, sodium, creatinine, hematocrit, ALT, and γ-GT and between IO and venous samples were small at baseline and after hemorrhage while differences for lactate and glucose increased with hypovolemia. Both IO-arterial and venoarterial differences in acid-base parameters increased with hypovolemia. Dispersions of differences were often large.

    Conclusions: Average levels of blood gases, acid base parameters, hematocrit, CK, AST, γ-GT, creatinine, and ALT, but not lactate and glucose, were similar in IO and venous samples in hypovolemia. However, precision was limited, indicating that IO test results should be confirmed when other vascular access is established, and that analysis of IO samples should be limited to acute situations and not used for detailed diagnostics in this setting.

  • 72.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Eriksson, Mats B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lubenow, Norbert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Analysis of Thromboelastography, PT, APTT and Fibrinogen in Intraosseous and Venous Samples: An Experimental Study2016Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 24, artikel-id 131Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:Laboratory analysis of coagulation is often important in emergencies. If vascular access is challenging,intraosseous catheterization may be necessary for treatment. We studied the analysis of coagulation parameters inintraosseous aspirate during stable conditions and after major haemorrhage in a porcine model.Methods:Ten anesthetized pigs received central venous and intraosseous catheters and samples were taken foranalysis of thromboelastography (TEG), prothrombin time (PT), activated partial thromboplastin time (APTT) andfibrinogen concentration. Analyses were repeated after removal of 50 % of the calculated blood volume andresuscitation with crystalloid. Intraosseous and venous values were compared.Results:Bleeding and resuscitation resulted in haemodilution and hypotension. Median TEG reaction time wasshorter in intraosseous than in venous samples before (1.6 vs 4.6 min) and after (1.6 vs 4.7 min) haemodilution.Median maximal amplitude was smaller in intraosseous samples at baseline (68.3 vs 76.4 mm). No major differenceswere demonstrated for the other TEG parameters. The intraosseous samples often coagulated in vitro, makinganalysis of PT, APTT and fibrinogen difficult. After haemodilution, TEG maximal amplitude andα-angle, andfibrinogen concentration, were decreased and PT increased.Discussion:The intraosseous samples were clinically hypercoagulable and the TEG demonstrated a shortenedreaction time. The reason for this may hypothetically be found in the composition of the IO aspirate or in thesampling technique. After 50 % haemorrhage and haemodilution, a clinically relevant decrease in fibrinogenconcentration and a lower TEG maximal amplitude were observed.Conclusions:Although the sample is small, these data indicate that intraosseous samples are hypercoagulable,which may limit their usefulness for coagulation studies. Major haemodilution only moderately affected the studied parameters.

  • 73.
    Strandberg, Gunnar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Walther, Sten
    Uppsala Univ, Uppsala, Sweden..
    Öhman, Christina Agvald
    Uppsala Univ, Uppsala, Sweden..
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Long-term mortality after severe sepsis and septic shock in Swedish intensive care units 2005-20152017Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, nr 8, s. 1039-1039Artikel i tidskrift (Övrigt vetenskapligt)
  • 74. Suzuki, Satoshi
    et al.
    Woinarski, Nicholas C. Z.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Candal, Cristina Lluch
    Schneider, Antoine G.
    Glassford, Neil J.
    Eastwood, Glenn M.
    Bellomo, Rinaldo
    Pulse pressure variation-guided fluid therapy after cardiac surgery: A pilot before-and-after trial2014Ingår i: Journal of critical care, ISSN 0883-9441, E-ISSN 1557-8615, Vol. 29, nr 6, s. 992-996Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: The aim of this study is to study the feasibility, safety, and physiological effects of pulse pressure variation (PPV)-guided fluid therapy in patients after cardiac surgery. Materials and methods: We conducted a pilot prospective before-and-after study during mandatory ventilation after cardiac surgery in a tertiary intensive care unit. We introduced a protocol to deliver a fluid bolus for a PPV >= 13% for at least >10 minutes during the intervention period. Results: We studied 45 control patients and 53 intervention patients. During the intervention period, clinicians administered a fluid bolus on 79% of the defined PPV trigger episodes. Median total fluid intake was similar between 2 groups during mandatory ventilation (1297 mL[interquartile range 549-1968] vs 1481 mL [807-2563]; P =. 17) and the first 24 hours (3046 mL [interquartile range 2317-3982] vs 3017 mL [2192-4028]; P = .73). After adjusting for several baseline factors, PPV-guided fluid management significantly increased fluid intake during mandatory ventilation (P = .004) but not during the first 24 hours (P = .47). Pulse pressure variation-guided fluid therapy, however, did not significantly affect hemodynamic, renal, and metabolic variables. No serious adverse events were noted. Conclusions: Pulse pressure variation-guided fluid management was feasible and safe during mandatory ventilation after cardiac surgery. However, its advantages may be clinically small.

  • 75.
    Söderberg, Ewa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Eriksson, Mats B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Counteraction of early circulatory derangement by administration of low dose steroid treatment at the onset of established endotoxemic shock is not directly mediated by TNF-α and IL-62012Ingår i: Steroids, ISSN 0039-128X, E-ISSN 1878-5867, Vol. 77, nr 11, s. 1101-1106Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Once a septic condition is progressing, administration of steroids in the pro-inflammatory phase of septic shock ought to yield maximal effect on the subsequent, devastating inflammatory response. Recently, a retrospective study showed that early initiation of corticosteroid therapy improved survival in septic shock. We aimed to prospectively evaluate effects of early administrated hydrocortisone therapy on physiologic variables in a porcine model of septic shock.

    EXPERIMENT:

    Eight anesthetized pigs were given a continuous infusion of endotoxin during this 6h prospective, randomized, parallel-grouped placebo-controlled experimental study. At the onset of endotoxemic shock, defined as the moment when the mean pulmonary arterial pressure reached the double baseline value, the pigs were either given a single intravenous dose of hydrocortisone (5 mg kg−1) or the corresponding volume of saline.

    RESULTS:

    Mean arterial pressure and systemic vascular resistance index were significantly higher (both p<0.05), and heart rate was significantly lower (p<0.05), in the endotoxin+hydrocortisone group as compared to the endotoxin+saline group. Body temperature and blood hemoglobin levels increased significantly in the endotoxin+saline group (both p<0.05). Urinary hydrocortisone increased significantly in both groups (p<0.05). There were no significant differences in the plasma levels of TNF-alpha, IL-6 or nitrite/nitrate between the groups.

    CONCLUSION:

    Early treatment with hydrocortisone ameliorates some endotoxin mediated circulatory derangements, fever response and microvascular outflow. Our results suggest that these effects are not directly mediated by the pro-inflammatory cytokines TNF-alpha or IL-6, nor by NO.

  • 76.
    Thorsted, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Bouchene, Salim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Tano, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin. Uppsala Univ Hosp, Sect Clin Microbiol & Infect Med, Dept Med Sci, Uppsala, Sweden.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Karolinska Univ Hosp, Div Perioperat Med & Intens Care, Stockholm, Sweden;Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala Univ Hosp, Dept Surg Sci, Sect Anesthesiol & Intens Care, Hedenstierna Lab, Uppsala, Sweden.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala Univ Hosp, Infect Dis Sect, Dept Med Sci, Uppsala, Sweden.
    Karlsson, Mats O
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Friberg, Lena E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Nielsen, Elisabet I.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    A non-linear mixed effect model for innate immune response: In vivo kinetics of endotoxin and its induction of the cytokines tumor necrosis factor alpha and interleukin-62019Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 2, artikel-id e0211981Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Endotoxin, a component of the outer membrane of Gram-negative bacteria, has been extensively studied as a stimulator of the innate immune response. However, the temporal aspects and exposure-response relationship of endotoxin and resulting cytokine induction and tolerance development is less well defined. The aim of this work was to establish an in silico model that simultaneously captures and connects the in vivo time-courses of endotoxin, tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and associated tolerance development. Data from six studies of porcine endotoxemia in anesthetized piglets (n = 116) were combined and used in the analysis, with purified endotoxin (Escherichia coli O111: B4) being infused intravenously for 1-30 h in rates of 0.063-16.0 mu g/kg/h across studies. All data were modelled simultaneously by means of importance sampling in the non-linear mixed effects modelling software NONMEM. The infused endotoxin followed one-compartment disposition and non-linear elimination, and stimulated the production of TNF-alpha to describe the rapid increase in plasma concentration. Tolerance development, observed as declining TNF-alpha concentration with continued infusion of endotoxin, was also driven by endotoxin as a concentration-dependent increase in the potency parameter related to TNF-alpha production (EC50). Production of IL-6 was stimulated by both endotoxin and TNF-a, and four consecutive transit compartments described delayed increase in plasma IL-6. A model which simultaneously account for the time-courses of endotoxin and two immune response markers, the cytokines TNF-alpha and IL-6, as well as the development of endotoxin tolerance, was successfully established. This model-based approach is unique in its description of the time-courses and their interrelation and may be applied within research on immune response to bacterial endotoxin, or in pre-clinical pharmaceutical research when dealing with study design or translational aspects.

  • 77.
    von Seth, Magnus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Engström, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Maripuu, Enn
    Department of Medical Physics, University Hospital, Uppsala, Sweden.
    Widström, Charles
    Department of Medical Physics, University Hospital, Uppsala, Sweden.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Rapid Bolus Administration Does Not Increase the Extravasation Rate of Albumin: A Randomized Controlled Trial in the Endotoxemic Pig2017Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 47, nr 4, s. 514-519Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Some experimental data suggest that rapid bolus administration of albumin causes less plasma-expanding effects than slow, continuous infusion. To determine whether rapid bolus administration, in comparison with slow infusion, results in greater extravasation of albumin in experimental septic shock we performed a randomized controlled trial with 32 endotoxemic pigs. The animals were monitored and ventilated with standard intensive care equipment and given 10 mL x kg 5% albumin labeled with Technetium-99m, either as a rapid 15-minute bolus (Bolus group, n = 16) or as a 2-hour (h) infusion (Infusion group, n = 16). Radioactivity was monitored in plasma, extracellular microdialysate and urine for 6 h. Physiological parameters were monitored hourly. Radioactivity in the liver, spleen, kidney and lung was analyzed post-mortem.The plasma area under the curve (AUC) activity0-6h was 4.4 ± 0.9 x 10 in the Bolus group and 4.4 ± 1.1 x 10 counts x min x mL x h in the Infusion group. Blood hemoglobin levels increased in both groups, suggesting severe capillary leakage. Yet, there were no group differences in albumin radioactivity in plasma, muscle tissue, urine or in the post-mortem analysis of the organs. Following albumin administration, circulatory and respiratory parameters were similar in the two groups.In conclusion, the present results suggest that albumin might be given as a bolus without leading to increased extravasation of albumin, in contrast to previous animal experiments in rodents.

  • 78.
    von Seth, Magnus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Effects of Tigecycline and Doxycycline on Inflammation and Hemodynamics in Porcine Endotoxemia: a Prospective, Randomized and Placebo Controlled Trial2015Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 43, nr 6, s. 604-611Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Antibiotics might, apart from an antimicrobial effect, also exert anti-inflammatory effects. The novel antibiotic tigecycline, potentially useful in septic shock from Gram-negative multi-resistant bacteria, is structurally related to antibiotics with known anti-inflammatory properties. However, its anti-inflammatory effects have previously not been explored in vivo. Using a sterile integrative porcine sepsis model, we investigated the anti-inflammatory and circulatory effects of tigecycline in comparison to doxycycline and placebo.

    METHODS: Eighteen pigs were randomized to receive tigecycline 100 mg, doxycycline 200 mg or placebo and subjected to 6 h endotoxin infusion at 0.5 μg x kg x h. Markers of inflammation, nitric oxide (NO) production, vascular permeability, hemodynamics, organ dysfunction, tissue metabolism and acid-base parameters were monitored.

    RESULTS: Peak plasma tumor necrosis alpha (TNF-α) was lower in the doxycycline group (P=0.031) but not in the tigecycline group (P=0.86) compared to placebo with geometric mean plasma concentrations of 16, 79 and 63 ng x ml, respectively. Mean arterial pressure was higher 4-6 h in the tigecycline group with values at 6 h of 107± 9 mmHg compared to the placebo and doxycycline groups (85 ± 27 mmHg and 90 ± 32 mmHg, respectively) (P=0.025). The white blood cell and the neutrophil granulocyte counts were less reduced in the doxycycline group, but not in the tigecycline group at 4-6 h (P=0.009 and p=0.019, respectively). Other markers of inflammation, organ dysfunction, tissue metabolism and acid-base parameters were unaffected by tigecycline.

    CONCLUSIONS: Consistent with known anti-inflammatory properties, doxycycline yielded decreased TNF-α levels. Tigecycline did not affect cytokine levels but counteracted hypotension and hypoperfusion.

  • 79. Woinarski, Nicholas C. Z.
    et al.
    Suzuki, Satoshi
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lumsden, Natalie
    Chin-Dusting, Jaye
    Schneider, Antoine G.
    Bailey, Michael
    Bellomo, Rinaldo
    Near-infrared spectroscopy of the thenar eminence to estimate forearm blood flow2013Ingår i: Critical Care and Resuscitation, ISSN 1441-2772, Vol. 15, nr 4, s. 323-326Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Near-infrared spectroscopy of the thenar eminence (NIRSth) can be used at the bedside to assess tissue oxygenation (Sto(2)), the reperfusion response to ischaemia and the tissue haemoglobin index (THI). Its ability to estimate forearm blood flow (FBF) has not previously been assessed. Objectives: We aimed to test whether short-lived venous occlusion-induced changes in NIRSth-derived THI (Delta THI/minute) correlate with strain gauge plethysmography (SGP) measurements. Methods: We measured FBF in nine volunteers with SGP by venous occlusion, while estimating Delta THI. Measurements were obtained in two forearm positions (elevated and horizontal) at baseline and during induced hyperaemia. Results: We performed 246 paired measurements at rest and after occlusion-induced hyperaemia. At rest, mean SGP-estimated FBF was 3.5-3.6 mL/dL/minute at baseline, compared with 12.9-13.6 mL/dL/minute during hyperaemia. At rest, Delta THI was 6.1-8.2/minute, compared with 29.7-32.5/minute during hyperaemia. Delta THI was a significant predictor of SGP FBF (P<0.01), with stronger correlation during hyperaemia (P<0.01). An equation was developed to convert Delta THI/minute into FBF at mL/dL/minute (FBF=0.362 x Delta THI/minute + 0.864). Conclusions: NIRSth can be used to estimate FBF. Given its portability and its ability to also measure Sto(2) and vascular reactivity, NIRSth can assist in providing a comprehensive bedside assessment of the forearm circulation in critically ill patients.

  • 80.
    Åkerfeldt, Torbjörn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Gunningberg, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Swenne, Christine, Leo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Serum leptin is decreased thirty days after surgery2014Ingår i: Journal of Diabetes and Metabolism, ISSN 2155-6156, Vol. 5, nr 12Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Leptin plays an important role for the regulation of food intake, energy expenditure and glucose control. The aim of this study was to study the effect of surgery on circulating levels of human leptin in a human elective surgery model. Methods: A prospective observational study was conducted. Blood sampling was carried out prior to surgery and four and thirty days after elective surgery, respectively. Patients undergoing orthopedic surgery (n=29) and coronary bypass patients (n=21) were included in the study. Serum leptin levels were measured using sandwich ELISA. C-reactive protein (CRP) was analyzed by turbidimetry. Results: Leptin values was significantly decreased thirty days after surgery in both orthopedic (p=0.002) and coronary bypass patients (p=0.003) in comparison with presurgical values. Conclusion: Elective surgery is associated with decreased leptin levels in the late postsurgical phase.

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