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- Kander, Thomas
(author)
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Aspects of bleeding complications and hemostasis at central line insertion and mild induced hypothermia
- 2014
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Doctoral thesis (other academic/artistic)abstract
- Bleeding complications range from 0.5 to 1.6% in connection with central venous catheter insertions but are more frequent in patients with bone marrow failure and severe thrombocytopenia. Although supportive evidence is scarce, prophylactic platelet transfusion is sometimes performed in these patients before catheter insertion. Furthermore, the ideal threshold platelet count and timing of transfusion remain controversial among clinical studies. Hypothermia is generally considered to reduce coagulation and platelet function. However, studies performed in animals, healthy volunteers, and patients have shown conflicting results. Paper I, a retrospective study in non-intensive care unit patients, showed that serious bleeding complications in association with central line insertions were uncommon and that insertion of a large bore catheter may be an independent risk factor for mild bleeding complications in this population. Paper II, a prospective observational study, evaluated the efficacy of prophylactic platelet transfusions in thrombocytopenic patients with bone marrow failure. Transfusion improved hemostatic parameters in ROTEM and Multiplate tests by increasing the number of platelets and not by enhancing platelet function. Improved clotting parameters persisted between 1 and 4 hours after transfusion. Paper III demonstrated increased platelet aggregation and strengthened clot formation over time in out-of-hospital cardiac arrest patients treated with hypothermia. In patients with dual platelet inhibition, including ticagrelor and aspirin, this effect was offset by powerful P2Y12 blockade, confirmed by analysis of vasodilator-stimulated phosphoprotein. The effect of ticagrelor was delayed in survivors of cardiac arrest, probably due to slow gastric emptying. Paper IV demonstrated prolonged clot initiation and decreased clot propagation in ROTEM testing (EXTEM, FIBTEM, and APTEM assays) in whole blood from out-of-hospital cardiac arrest patients treated with mild induced hypothermia. Paper V investigated whole blood from acute coronary syndrome patients treated with ticagrelor and aspirin. In vitro applied hypothermia to 33 degrees C markedly increased platelet activity measured by flow cytometry, whereas a viscoelastic coagulation test (Sonoclot) revealed a hypocoagulative response.
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- Kander, Thomas, et al.
(author)
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Bleeding complications after central line insertions: relevance of pre-procedure coagulation tests and institutional transfusion policy.
- 2013
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 57:5, s. 573-579
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Journal article (peer-reviewed)abstract
- BACKGROUND: The aim of this study was to map pre-procedural variables for insertion of a central venous catheter, prophylactic blood component use and to investigate whether any independent variable could be identified as an independent risk factor for associated bleeding complications in patients outside the intensive care unit. METHODS: In this retrospective study, we investigated 1737 consecutive insertions of central venous catheters in 1444 patients in a large university hospital during 2009-2010. Pre-procedural coagulation status, blood component use, type of catheter, insertion site and complications during insertion were recorded and compared with bleeding complications documented on electronic charts. RESULTS: No serious bleeding complications were recorded in connection with the insertion of central venous catheters. Sixteen of 1769 (0.9%) insertions caused grade 2 bleeding, defined as bleeding requiring prolonged compression at the insertion site. Insertion of a large bore central dialysis catheter was found to be an independent risk factor for bleeding complications. Neither conventional coagulation tests nor accidental arterial puncture or the number of needle passes could predict bleeding complications in this study. CONCLUSION: This retrospective study, in non-ICU patients, shows that serious bleeding complications in association with central line insertions are uncommon and that insertion of a large bore catheter is likely to be an independent risk factor for mild-bleeding complications in this population.
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- Kander, Thomas, et al.
(author)
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Platelet aggregation and clot formation in comatose survivors of cardiac arrest treated with induced hypothermia and dual platelet inhibition with aspirin and ticagrelor; a prospective observational study
- 2014
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In: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 18:5
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Journal article (peer-reviewed)abstract
- Introduction: We conducted a prospective observational study in cardiac arrest survivors treated with mild induced hypothermia, evaluating different platelet function tests at hypo-and normothermia. We also investigated the relation between gastric emptying and vasodilator stimulated phosphoprotein (VASP). Methods: Comatose survivors of out of hospital cardiac arrest were included and divided into two groups, depending on whether dual platelet inhibition with peroral ticagrelor and aspirin was given or not. The first blood samples (T1) were collected 12-24 hours after reaching target temperature (33 degrees C) and were compared to blood samples collected 12-28 hours after reaching normothermia (37 degrees C) (T2) within each group. All samples were analysed by Sonoclot viscoelasticity, flow cytometry based VASP and with multiple electrode aggregometry, Multiplate (R); adenosine diphosphate (ADP), collagen (COL), thrombin receptor agonist peptide (TRAP) and arachidonic acid (ASPI). Sonoclot and Multiplate (R) instruments were set on in vivo temperatures. Gastric secretion from the nasogastric tube was measured to assess absorption of per orally administered antiplatelet drugs. Differences between T1 and T2 within each group were calculated using Wilcoxon matched pairs signed test. Significance levels were set at P < 0.01. Results: In total, 23 patients were included. In patients with dual platelet inhibition (n = 14) Multiplate (R)-analyses showed no changes in ADP stimulated platelets. COL, TRAP and ASPI aggregations were higher at T2 compared to T1. Sonoclot-analyses showed that activated clotting time (ACT) was unchanged but both clot rate (CR) and platelet function (PF) were higher at T2 compared to T1. VASP decreased from 53 +/- 28(T1) to 24 +/- 22(T2), (P < 0.001). The average volume of gastric secretion aspirated before T1 correlated well with VASP (T1), r = 0.81 (P < 0.001). In patients with no platelet inhibition, (n = 9) similar changes between T1 and T2 were seen as in patients with dual platelet inhibition while VASP was unchanged. Conclusions: We have demonstrated increased platelet aggregation and strengthened clot formation over time in out of hospital cardiac arrest patients treated with hypothermia. In patients on oral dual platelet inhibition, the effect of ticagrelor was delayed, probably due to slow gastric emptying.
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| 9. |
- Kander, Thomas, et al.
(author)
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Wide Temperature Range Testing with ROTEM Coagulation Analyses.
- 2014
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In: Therapeutic hypothermia and temperature management. - : Mary Ann Liebert Inc. - 2153-7933 .- 2153-7658. ; 4:3, s. 125-130
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Journal article (peer-reviewed)abstract
- Mild induced hypothermia is used for neuroprotection in patients successfully resuscitated after cardiac arrest. Temperature-dependent effects on rotational thromboelastometry (ROTEM(®)) assays with EXTEM(®), FIBTEM(®), or APTEM(®) in cardiac arrest patients have not previously been studied. Ten patients with out-of-hospital cardiac arrest who underwent induced hypothermia were studied during stable hypothermia at 33°C. ROTEM temperature effects on EXTEM, FIBTEM, and APTEM assays were studied at temperatures set between 30°C and 42°C. Citrated whole blood test tubes were incubated in temperature-adjusted heating blocks and then investigated at respective temperature in the temperature-adjusted ROTEM. The following variables were determined: clotting time (CT), clot formation time (CFT), α-angle, and maximum clot firmness (MCF). The results from hypo- and hyperthermia samples were compared with the samples incubated at 37°C using the Wilcoxon matched-pairs signed-rank test. A p-value of <0.05 was considered significant. CT-EXTEM(®) and CT-APTEM(®) were prolonged by hypothermia at 30°C (p<0.01 for both) and 33°C (p<0.05 for both). Hyperthermia at 42°C shortened CT-EXTEM (p<0.05) and CT-APTEM (p<0.01). CFT-EXTEM(®) and CFT-APTEM(®) were markedly prolonged by hypothermia at 30°C, 33°C, and 35°C (p<0.01 for all except CFT-EXTEM, 35°C [p<0.05]). The α-angle-EXTEM was markedly decreased at 30°C, 33°C, and 35°C (p<0.01) but increased at 40°C (p<0.05) and 42°C (p<0.01); α-angle-APTEM showed similar results. MCF was unchanged at different temperatures for all tests. ROTEM (EXTEM, FIBTEM, and APTEM assays) revealed a hypocoagulative response to in vitro-applied hypothermia in the blood of cardiac arrest patients reflected in the prolonged clot initiation and decreased clot propagation. Hyperthermia showed the opposite effects. Clot firmness was not affected by temperature.
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- Nielsen, Niklas, et al.
(author)
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Targeted Temperature Management at 33 degrees C versus 36 degrees C after Cardiac Arrest
- 2013
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In: New England Journal of Medicine. - 0028-4793. ; 369:23, s. 2197-2206
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Journal article (peer-reviewed)abstract
- BackgroundUnconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. MethodsIn an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33 degrees C or 36 degrees C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. ResultsIn total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33 degrees C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36 degrees C group (225 of 466 patients) (hazard ratio with a temperature of 33 degrees C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33 degrees C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36 degrees C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. ConclusionsIn unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33 degrees C did not confer a benefit as compared with a targeted temperature of 36 degrees C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.)
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