Publications by authors named "Nicole P Juffermans"

227 Publications

Transfusion strategies in bleeding critically ill adults: a clinical practice guideline from the European Society of Intensive Care Medicine.

Intensive Care Med 2021 Dec 22;47(12):1368-1392. Epub 2021 Oct 22.

Department of Medicine, McMaster University, Hamilton, Canada.

Purpose: To develop evidence-based clinical practice recommendations regarding transfusion practices and transfusion in bleeding critically ill adults.

Methods: A taskforce involving 15 international experts and 2 methodologists used the GRADE approach to guideline development. The taskforce addressed three main topics: transfusion support in massively and non-massively bleeding critically ill patients (transfusion ratios, blood products, and point of care testing) and the use of tranexamic acid. The panel developed and answered structured guideline questions using population, intervention, comparison, and outcomes (PICO) format.

Results: The taskforce generated 26 clinical practice recommendations (2 strong recommendations, 13 conditional recommendations, 11 no recommendation), and identified 10 PICOs with insufficient evidence to make a recommendation.

Conclusions: This clinical practice guideline provides evidence-based recommendations for the management of massively and non-massively bleeding critically ill adult patients and identifies areas where further research is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00134-021-06531-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8532090PMC
December 2021

Plasma and rhADAMTS13 reduce trauma-induced organ failure by restoring the ADAMTS13-VWF axis.

Blood Adv 2021 09;5(17):3478-3491

Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Trauma-induced organ failure is characterized by endothelial dysfunction. The aim of this study was to investigate the role of von Willebrand factor (VWF) and its cleaving enzyme, ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13) in the occurrence of endothelial permeability and organ failure in trauma. In an observational study in a level-1 trauma center, 169 adult trauma patients with clinical signs of shock and/or severe injuries were included. Trauma was associated with low ADAMTS13 and high VWF antigen levels, thus generating an imbalance of ADAMTS13 to VWF. Patients who developed organ failure (23%) had greater ADAMTS13-to-VWF imbalances, persistently lower platelet counts, and elevated levels of high-molecular-weight VWF multimers compared with those without organ failure, suggesting microthrombi formation. To investigate the effect of replenishing low ADAMTS13 levels on endothelial permeability and organ failure using either recombinant human ADAMTS13 (rhADAMTS13) or plasma transfusion, a rat model of trauma-induced shock and transfusion was used. Rats in traumatic hemorrhagic shock were randomized to receive crystalloids, crystalloids supplemented with rhADAMTS13, or plasma transfusion. A 70-kDa fluorescein isothiocyanate-labeled dextran was injected to determine endothelial leakage. Additionally, organs were histologically assessed. Both plasma transfusion and rhADAMTS13 were associated with a reduction in pulmonary endothelial permeability and organ injury when compared with resuscitation with crystalloids, but only rhADAMTS13 resulted in significant improvement of a trauma-induced decline in ADAMTS13 levels. We conclude that rhADAMTS13 and plasma transfusion can reduce organ failure following trauma. These findings implicate the ADAMTS13-VWF axis in the pathogenesis of organ failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2021004404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525227PMC
September 2021

Venous thromboembolism is not a risk factor for the development of bloodstream infections in critically ill COVID-19 patients.

Thromb Res 2021 10 25;206:128-130. Epub 2021 Aug 25.

Department of Intensive Care, OLVG Hospital, Amsterdam, the Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2021.08.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384728PMC
October 2021

Differential effects of speed and volume on transfusion-associated circulatory overload: A randomized study in rats.

Vox Sang 2021 Aug 15. Epub 2021 Aug 15.

Department of Intensive Care, Amsterdam UMC, Amsterdam, The Netherlands.

Background And Objectives: Transfusion-associated circulatory overload (TACO) is the primary cause of transfusion-related mortality. Speed and volume of transfusion are major risk factors. The aim of this study was to investigate the interaction of red blood cell (RBC) transfusion speed and volume on the development of TACO.

Materials And Methods: A validated model for TACO in anaemic Lewis rats with an acute myocardial infarction was used. The effect on pulmonary hydrostatic pressure of one, two or four units of packed RBCs transfused in either 30 or 60 min was evaluated (3.3-26.6 ml·kg ·hr ). Pulmonary capillary pressure was measured as left ventricular end-diastolic pressure (LVEDP). Cardiac stress biomarkers atrial natriuretic-peptide (ANP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured 1-h post-transfusion.

Results: Thirty animals were included (n = 5 per group). Transfusion of RBCs increased LVEDP in a volume-dependent manner (ΔLVEDP [mmHg]: -0.95, +0.50, +6.26, p < 0.001). Fast transfusion increased overall ΔLVEDP by +3.5 mmHg and up to +11.8 mmHg in the four units' group (p = 0.016). Doubling transfusion speed increased ΔLVEDP more than doubling volume in the larger volume groups. No difference in ANP or NT-proBNP were seen in high transfusion volume or groups.

Conclusion: Transfusion volume dose-dependently increased LVEDP, with speed of transfusion rapidly elevating LVEDP at higher transfusion volumes. ANP and NT-proBNP were not impacted by transfusion volume or speed in this model. TACO is seen as purely volume overload, however, this study emphasizes that limiting transfusion speed, as a modifiable risk factor, might aid in preventing TACO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/vox.13191DOI Listing
August 2021

A Large Retrospective Assessment of Voriconazole Exposure in Patients Treated with Extracorporeal Membrane Oxygenation.

Microorganisms 2021 Jul 20;9(7). Epub 2021 Jul 20.

Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.

Background: Voriconazole is one of the first-line therapies for invasive pulmonary aspergillosis. Drug concentrations might be significantly influenced by the use of extracorporeal membrane oxygenation (ECMO). We aimed to assess the effect of ECMO on voriconazole exposure in a large patient population.

Methods: Critically ill patients from eight centers in four countries treated with voriconazole during ECMO support were included in this retrospective study. Voriconazole concentrations were collected in a period on ECMO and before/after ECMO treatment. Multivariate analyses were performed to evaluate the effect of ECMO on voriconazole exposure and to assess the impact of possible saturation of the circuit's binding sites over time.

Results: Sixty-nine patients and 337 samples (190 during and 147 before/after ECMO) were analyzed. Subtherapeutic concentrations (<2 mg/L) were observed in 56% of the samples during ECMO and 39% without ECMO ( = 0.80). The median trough concentration, for a similar daily dose, was 2.4 (1.2-4.7) mg/L under ECMO and 2.5 (1.4-3.9) mg/L without ECMO ( = 0.58). Extensive inter-and intrasubject variability were observed. Neither ECMO nor squared day of ECMO (saturation) were retained as significant covariates on voriconazole exposure.

Conclusions: No significant ECMO-effect was observed on voriconazole exposure. A large proportion of patients had voriconazole subtherapeutic concentrations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms9071543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303158PMC
July 2021

Prophylactic plasma: Can we finally let go?

Transfusion 2021 07;61(7):1991-1992

Department of Intensive Care Medicine, Amsterdam UMC, Amsterdam, The Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/trf.16546DOI Listing
July 2021

Platelet-to-red blood cell ratio and mortality in bleeding trauma patients: A systematic review and meta-analysis.

Transfusion 2021 07;61 Suppl 1:S243-S251

Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Background: In traumatic bleeding, transfusion practice has shifted toward higher doses of platelets and plasma transfusion. The aim of this systematic review was to investigate whether a higher platelet-to-red blood cell (RBC) transfusion ratio improves mortality without worsening organ failure when compared with a lower ratio of platelet-to-RBC.

Methods: Pubmed, Medline, and Embase were screened for randomized controlled trials (RCTs) in bleeding trauma patients (age ≥16 years) receiving platelet transfusion between 1946 until October 2020. High platelet:RBC ratio was defined as being the highest ratio within an included study. Primary outcome was 24 hour mortality. Secondary outcomes were 30-day mortality, thromboembolic events, organ failure, and correction of coagulopathy.

Results: In total five RCTs (n = 1757 patients) were included. A high platelet:RBC compared with a low platelet:RBC ratio significantly improved 24 hour mortality (odds ratio [OR] 0.69 [0.53-0.89]) and 30- day mortality (OR 0.78 [0.63-0.98]). There was no difference between platelet:RBC ratio groups in thromboembolic events and organ failure. Correction of coagulopathy was reported in five studies, in which platelet dose had no impact on trauma-induced coagulopathy.

Conclusions: In traumatic bleeding, a high platelet:RBC improves mortality as compared to low platelet:RBC ratio. The high platelet:RBC ratio does not influence thromboembolic or organ failure event rates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/trf.16455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362120PMC
July 2021

Incidence, Clinical Characteristics and Outcomes of Early Hyperbilirubinemia in Critically ill Patients - Insights From The Mars Study.

Shock 2021 Jul 7. Epub 2021 Jul 7.

Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands: Department of Anesthesiology Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands: Department of Intensive Care Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands: Research VUmc Intensive Care (REVIVE) Amsterdam UMC, Universiteit van Amsterdam, Amsterdam, The Netherlands: Department of Intensive Care Amsterdam UMC, Universiteit van Amsterdam, Amsterdam, The Netherlands: Department of Pulmonology Amsterdam UMC, Universiteit van Amsterdam, Amsterdam, The Netherlands: Department of Gastroenterology and Hepatology Amsterdam UMC, Universiteit van Amsterdam, Amsterdam, The Netherlands: Division of Infectious Diseases Amsterdam UMC, Universiteit van Amsterdam, Amsterdam, The Netherlands: Center for Experimental and Molecular Medicine (CEMM) OLVG hospital, Amsterdam, The Netherlands: Department of Intensive Care Medicine University Medical Center Utrecht, Utrecht, The Netherlands: Department of Intensive Care Medicine University Medical Center Utrecht, Utrecht, The Netherlands: Department of Medical Microbiology Mahidol University, Bangkok, Thailand: Mahidol-Oxford Tropical Medicine Research Unit (MORU) Mahidol University, Bangkok, Thailand: University of Oxford, Oxford, UK: Nuffield Department of Medicine.

Objective: To investigate the incidence, clinical characteristics and outcomes of early hyperbilirubinemia in critically ill patients.

Design And Setting: This is a post-hoc analysis of a prospective multicenter cohort study.

Patients: Patients with measured bilirubin levels within the first 2 days after ICU admission were eligible. Patients with liver cirrhosis were excluded.

Endpoints: The primary endpoint was the incidence of early hyperbilirubinemia, defined as bilirubin ≥ 33 μmol/L within 2 days after ICU admission. Secondary endpoints included clinical characteristics of patients with versus patients without early hyperbilirubinemia, and outcomes up to day 30.

Results: Of 4836 patients, 559 (11.6%) patients had early hyperbilirubinemia. Compared to patients without early hyperbilirubinemia, patients with early hyperbilirubinemia presented with higher severity of illness scores, and higher incidences of sepsis and organ failure. After adjustment for confounding variables, early hyperbilirubinemia remained associated with mortality at day 30 (odds ratio, 1.31 [95%-confidence interval 1.06-1.60]; p = 0.018). Patients with early hyperbilirubinemia and thrombocytopenia (interaction p-value = 0.005) had a higher likelihood of death within 30 days (odds ratio, 2.61 [95%-confidence interval 2.08-3.27]; p < 0.001) than patients with early hyperbilirubinemia and a normal platelet count (odds ratio, 1.09 [95%-confidence interval 0.75-1.55]; p = 0.655).

Conclusions: Early hyperbilirubinemia occurs frequently in the critically ill, and these patients present with higher disease severity and more often with sepsis and organ failures. Early hyperbilirubinemia has an association with mortality, albeit this association was only found in patients with concomitant thrombocytopenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SHK.0000000000001836DOI Listing
July 2021

Effect of red blood cell transfusion on inflammation, endothelial cell activation and coagulation in the critically ill.

Vox Sang 2021 Jul 1. Epub 2021 Jul 1.

Department of Intensive Care Medicine and Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, Location VUmc, University of Amsterdam, Amsterdam, The Netherlands.

Background And Objectives: Red blood cell (RBC) transfusion is a frequently applied intervention in an intensive care unit. However, transfusion is associated with adverse outcomes including organ failure and thrombo-embolic events. Mechanisms of these effects are not known but may be related to activation of the endothelium or of the coagulation or inflammatory system. We hypothesized that a RBC transfusion in the critically ill would result in further activation of these systems.

Materials And Methods: In 74 non-bleeding critically ill patients receiving one RBC unit, markers of inflammation, endothelial cell activation and coagulation were measured before transfusion, at 1 h after transfusion and 24 h after transfusion. The impact of disease severity of the recipient on these changes was assessed by comparing septic and non-septic patients (according to sepsis-3 definition) and by correlation of biomarkers with the sequential organ failure assessment (SOFA) score.

Results: Levels of von Willebrand Factor (vWF), soluble ICAM-1, soluble thrombomodulin, fibrinogen and d-dimer were already high at baseline, whereas ADAMTS13 levels were low. VWF levels increased significantly 24 h after RBC transfusion (median 478% (338-597) vs. 526% (395-623), p = 0.009). The other biomarkers did not change significantly. Post transfusion change was not dependent on the presence of sepsis and was not correlated with SOFA score.

Conclusion: RBC transfusion in critically ill patients was associated with an increase in circulating vWF levels, suggesting a further increase in activation of the endothelium, a finding that was independent of the presence of sepsis or organ injury level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/vox.13125DOI Listing
July 2021

Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial.

Lancet Respir Med 2021 09 18;9(9):957-968. Epub 2021 Jun 18.

Department of Internal Medicine, Haaglanden Medisch Centrum, The Hague, Netherlands.

Background: The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak.

Methods: This randomised, double-blind, placebo-controlled, clinical trial was done at 13 academic and non-academic teaching hospitals in the Netherlands. Hospitalised patients (aged ≥18 years) with COVID-19, as confirmed by an RT-PCR test for SARS-CoV-2, requiring supplemental oxygen to maintain a peripheral oxygen saturation of greater than 94% were eligible. Patients were excluded if they had severe pre-existing pulmonary disease, had pre-existing heart failure, had undergone active treatment of a haematological or non-haematological malignancy in the previous 12 months, had cytopenia, or were receiving concomitant treatment with medication known to strongly interact with imatinib. Patients were randomly assigned (1:1) to receive either oral imatinib, given as a loading dose of 800 mg on day 0 followed by 400 mg daily on days 1-9, or placebo. Randomisation was done with a computer-based clinical data management platform with variable block sizes (containing two, four, or six patients), stratified by study site. The primary outcome was time to discontinuation of mechanical ventilation and supplemental oxygen for more than 48 consecutive hours, while being alive during a 28-day period. Secondary outcomes included safety, mortality at 28 days, and the need for invasive mechanical ventilation. All efficacy and safety analyses were done in all randomised patients who had received at least one dose of study medication (modified intention-to-treat population). This study is registered with the EU Clinical Trials Register (EudraCT 2020-001236-10).

Findings: Between March 31, 2020, and Jan 4, 2021, 805 patients were screened, of whom 400 were eligible and randomly assigned to the imatinib group (n=204) or the placebo group (n=196). A total of 385 (96%) patients (median age 64 years [IQR 56-73]) received at least one dose of study medication and were included in the modified intention-to-treat population. Time to discontinuation of ventilation and supplemental oxygen for more than 48 h was not significantly different between the two groups (unadjusted hazard ratio [HR] 0·95 [95% CI 0·76-1·20]). At day 28, 15 (8%) of 197 patients had died in the imatinib group compared with 27 (14%) of 188 patients in the placebo group (unadjusted HR 0·51 [0·27-0·95]). After adjusting for baseline imbalances between the two groups (sex, obesity, diabetes, and cardiovascular disease) the HR for mortality was 0·52 (95% CI 0·26-1·05). The HR for mechanical ventilation in the imatinib group compared with the placebo group was 1·07 (0·63-1·80; p=0·81). The median duration of invasive mechanical ventilation was 7 days (IQR 3-13) in the imatinib group compared with 12 days (6-20) in the placebo group (p=0·0080). 91 (46%) of 197 patients in the imatinib group and 82 (44%) of 188 patients in the placebo group had at least one grade 3 or higher adverse event. The safety evaluation revealed no imatinib-associated adverse events.

Interpretation: The study failed to meet its primary outcome, as imatinib did not reduce the time to discontinuation of ventilation and supplemental oxygen for more than 48 consecutive hours in patients with COVID-19 requiring supplemental oxygen. The observed effects on survival (although attenuated after adjustment for baseline imbalances) and duration of mechanical ventilation suggest that imatinib might confer clinical benefit in hospitalised patients with COVID-19, but further studies are required to validate these findings.

Funding: Amsterdam Medical Center Foundation, Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ZonMW, and the European Union Innovative Medicines Initiative 2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-2600(21)00237-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232929PMC
September 2021

The relation between fibrinogen level, neutrophil activity and nucleosomes in the onset of disseminated intravascular coagulation in the critically ill.

J Intern Med 2021 10 9;290(4):922-927. Epub 2021 Jul 9.

Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Background: Nucleosomes and neutrophil extracellular traps (NETs) are important in the pathophysiology of disseminated intravascular coagulation (DIC). Fibrinogen, as an acute phase reactant, may be protective by engaging neutrophils. We hypothesize that DIC can occur when NET formation becomes uncontrolled in relation to low fibrinogen levels.

Patients/method: The ratio of both circulating nucleosomes and human neutrophil elastase alpha-1-antitrypsine complexes (HNE-a1ATc) to fibrinogen was correlated to thrombocytopenia, DIC and organ failure in 64 critically ill coagulopathic patients.

Results: A high nucleosome to fibrinogen ratio correlated with thrombocytopenia and organ failure (ρ -0.391, p 0.01 and ρ 0.556, p 0.01, respectively). A high HNE-a1ATc to fibrinogen ratio correlated with thrombocytopenia, DIC and organ failure (ρ -0.418, p 0.01, ρ 0.391, p 0.01 and ρ 0.477, p 0.01 respectively).

Conclusion: These findings support the hypothesis that fibrinogen is protective against DIC by counterbalancing excessive neutrophil activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/joim.13346DOI Listing
October 2021

Population Pharmacokinetics and Probability of Target Attainment of Different Dosing Regimens of Ceftazidime in Critically Ill Patients with a Proven or Suspected Infection.

Antibiotics (Basel) 2021 May 21;10(6). Epub 2021 May 21.

Hospital Pharmacy and Clinical Pharmacology, Amsterdam University Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

Altered pharmacokinetics (PK) of hydrophilic antibiotics in critically ill patients is common, with possible consequences for efficacy and resistance. We aimed to describe ceftazidime population PK in critically ill patients with a proven or suspected infection and to establish optimal dosing. Blood samples were collected for ceftazidime concentration measurement. A population PK model was constructed, and probability of target attainment (PTA) was assessed for targets 100% T > MIC and 100% T > 4 × MIC in the first 24 h. Ninety-six patients yielded 368 ceftazidime concentrations. In a one-compartment model, variability in ceftazidime clearance (CL) showed association with CVVH. For patients not receiving CVVH, variability in ceftazidime CL was 103.4% and showed positive associations with creatinine clearance and with the comorbidities hematologic malignancy, trauma or head injury, explaining 65.2% of variability. For patients treated for at least 24 h and assuming a worst-case MIC of 8 mg/L, PTA was 77% for 100% T > MIC and 14% for 100% T > 4 × MIC. Patients receiving loading doses before continuous infusion demonstrated higher PTA than patients who did not (100% T > MIC: 95% ( = 65) vs. 13% ( = 15); < 0.001 and 100% T > 4 × MIC: 20% vs. 0%; = 0.058). The considerable IIV in ceftazidime PK in ICU patients could largely be explained by renal function, CVVH use and several comorbidities. Critically ill patients are at risk for underexposure to ceftazidime when empirically aiming for the breakpoint MIC for . A loading dose is recommended.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antibiotics10060612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224000PMC
May 2021

Induced normothermia ameliorates the procoagulant host response in human endotoxaemia.

Br J Anaesth 2021 Jun 23;126(6):1111-1118. Epub 2021 Apr 23.

Laboratory of Experimental Intensive Care and Anaesthesiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands; Department of Intensive Care Medicine, OLVG Hospital, Amsterdam, the Netherlands.

Background: Dysregulation of coagulation occurs commonly in sepsis, ranging from mild coagulopathy with decreased platelets to disseminated intravascular coagulation (DIC). We investigated the effect of induced normothermia on coagulation during lipopolysaccharide (LPS)-induced endotoxaemia in healthy volunteers.

Methods: Twelve volunteers received an infusion of bacterial lipopolysaccharide (Escherichia coli; 2 ng kg) and were assigned to either induced normothermia or control. Induced normothermia to maintain core temperature at 37°C consisted of external surface cooling, cold i.v. fluids, and medication to reduce shivering (buspirone, clonidine, and magnesium sulphate). The primary outcome was the DIC score (International Society on Thrombosis and Haemostasis guideline). Prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, plasma von Willebrand factor (vWf), and rotational thromboelastometry (ROTEM) were measured before and 1, 3, 6, and 8 h after LPS infusion. Differences between groups were tested with a mixed effects model.

Results: In control subjects, lipopolysaccharide caused a fever, transiently decreased platelet levels and lowered activated partial thromboplastin time, while prolonging prothrombin time and increasing D-Dimer and vWf levels. Normothermia prevented the DIC-score exceeding 4, which occurred in 50% of control subjects. Normothermia also reduced the fall in platelet count by 67x10 L([95%CI:27-107]; p=0.002), aPTT (mean difference:3s [95%CI:1-5]; p=0.005) and lowered vWf levels by 89% ([95%CI:6-172]; p=0.03), compared to the fever group. ROTEM measurements were unaffected by lipopolysaccharide.

Conclusion: In human endotoxaemia, induced normothermia decreases markers of endothelial activation and DIC. Maintaining normothermia may reduce coagulopathy in hyperinflammatory states.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bja.2021.02.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258978PMC
June 2021

Addressing gender imbalance in intensive care.

Crit Care 2021 04 16;25(1):147. Epub 2021 Apr 16.

Department of Anaesthesia and Intensive Care Medicine, Imperial College London, London, UK.

There is a large gender gap in critical care medicine with women underrepresented, particularly in positions of leadership. Yet gender diversity better reflects the current critical care community and has multiple beneficial effects at individual and societal levels. In this Viewpoint, we discuss some of the reasons for the persistent gender imbalance in critical care medicine, and suggest some possible strategies to help achieve greater equity and inclusion. An explicit and consistent focus on eliminating gender inequity is needed until gender diversity and inclusion become the norms in critical care medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-021-03569-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051087PMC
April 2021

Caging the dragon: Research approach to COVID-19-related thrombosis.

Res Pract Thromb Haemost 2021 Feb 8;5(2):278-290. Epub 2021 Mar 8.

Dept of Pulmonary Medicine Amsterdam Cardiovascular Sciences Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands.

The incidence of venous thrombosis, mostly pulmonary embolism (PE), ranging from local immunothrombosis to central emboli, but also deep vein thrombosis (DVT) in people with coronavirus disease 2019 (COVID-19) is reported to be remarkably high. The relevance of better understanding, predicting, treating, and preventing COVID-19-associated venous thrombosis meets broad support, as can be concluded from the high number of research, review, and guideline papers that have been published on this topic. The Dutch COVID & Thrombosis Coalition (DCTC) is a multidisciplinary team involving a large number of Dutch experts in the broad area of venous thrombosis and hemostasis research, combined with experts on virology, critically ill patients, pulmonary diseases, and community medicine, across all university hospitals and many community hospitals in the Netherlands. Within the consortium, clinical data of at least 5000 admitted COVID-19-infected individuals are available, including substantial collections of biobanked materials in an estimated 3000 people. In addition to considerable experience in preclinical and clinical thrombosis research, the consortium embeds virology-hemostasis research models within unique biosafety facilities to address fundamental questions on the interaction of virus with epithelial and vascular cells, in relation to the coagulation and inflammatory system. The DCTC has initiated a comprehensive research program to answer many of the current questions on the pathophysiology and best anticoagulant treatment of COVID-19-associated thrombotic complications. The research program was funded by grants of the Netherlands Thrombosis Foundation and the Netherlands Organization for Health Research and Development. Here, we summarize the design and main aims of the research program.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/rth2.12470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938618PMC
February 2021

Bosutinib reduces endothelial permeability and organ failure in a rat polytrauma transfusion model.

Br J Anaesth 2021 May 6;126(5):958-966. Epub 2021 Mar 6.

Laboratory of Experimental Intensive Care and Anesthesiology, Department of Trauma Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Intensive Care Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.

Background: Trauma-induced shock is associated with endothelial dysfunction. We examined whether the tyrosine kinase inhibitor bosutinib as an adjunct therapy to a balanced blood component resuscitation strategy reduces trauma-induced endothelial permeability, thereby improving shock reversal and limiting transfusion requirements and organ failure in a rat polytrauma transfusion model.

Methods: Male Sprague-Dawley rats (n=13 per group) were traumatised and exsanguinated until a MAP of 40 mm Hg was reached, then randomised to two groups: red blood cells, plasma and platelets in a 1:1:1 ratio with either bosutinib or vehicle. Controls were randomised to sham (median laparotomy, no trauma) with bosutinib or vehicle. Organs were harvested for histology and wet/dry (W/D) weight ratio.

Results: Traumatic injury resulted in shock, with higher lactate levels compared with controls. In trauma-induced shock, the resuscitation volume needed to obtain a MAP of 60 mm Hg was lower in bosutinib-treated animals (2.8 [2.7-3.2] ml kg) compared with vehicle (6.1 [5.1-7.2] ml kg, P<0.001). Lactate levels in the bosutinib group were 2.9 [1.7-4.8] mM compared with 6.2 [3.1-14.1] mM in the vehicle group (P=0.06). Bosutinib compared with vehicle reduced lung vascular leakage (W/D ratio of 5.1 [4.6-5.3] vs 5.7 [5.4-6.0] (P=0.046) and lung injury scores (P=0.027).

Conclusions: Bosutinib as an adjunct therapy to a balanced transfusion strategy reduced resuscitation volume, improved shock reversal, and reduced vascular leak and organ injury in a rat polytrauma model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bja.2021.01.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258973PMC
May 2021

How the COVID-19 pandemic will change the future of critical care.

Intensive Care Med 2021 Mar 22;47(3):282-291. Epub 2021 Feb 22.

School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

Coronavirus disease 19 (COVID-19) has posed unprecedented healthcare system challenges, some of which will lead to transformative change. It is obvious to healthcare workers and policymakers alike that an effective critical care surge response must be nested within the overall care delivery model. The COVID-19 pandemic has highlighted key elements of emergency preparedness. These include having national or regional strategic reserves of personal protective equipment, intensive care unit (ICU) devices, consumables and pharmaceuticals, as well as effective supply chains and efficient utilization protocols. ICUs must also be prepared to accommodate surges of patients and ICU staffing models should allow for fluctuations in demand. Pre-existing ICU triage and end-of-life care principles should be established, implemented and updated. Daily workflow processes should be restructured to include remote connection with multidisciplinary healthcare workers and frequent communication with relatives. The pandemic has also demonstrated the benefits of digital transformation and the value of remote monitoring technologies, such as wireless monitoring. Finally, the pandemic has highlighted the value of pre-existing epidemiological registries and agile randomized controlled platform trials in generating fast, reliable data. The COVID-19 pandemic is a reminder that besides our duty to care, we are committed to improve. By meeting these challenges today, we will be able to provide better care to future patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00134-021-06352-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898492PMC
March 2021

COVID-19: What we've done well and what we could or should have done better-the 4 Ps.

Crit Care 2021 01 28;25(1):40. Epub 2021 Jan 28.

Department of Anesthesiology and Intensive Care, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy.

The current coronavirus pandemic has impacted heavily on ICUs worldwide. Although many hospitals and healthcare systems had plans in place to manage multiple casualties as a result of major natural disasters or accidents, there was insufficient preparation for the sudden, massive influx of severely ill patients with COVID-19. As a result, systems and staff were placed under immense pressure as everyone tried to optimize patient management. As the pandemic continues, we must apply what we have learned about our response, both good and bad, to improve organization and thus patient care in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-021-03467-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841973PMC
January 2021

Continuous postoperative pericardial flushing reduces postoperative bleeding after coronary artery bypass grafting: A randomized trial.

EClinicalMedicine 2021 Jan 23;31:100661. Epub 2020 Dec 23.

Department of Cardiothoracic Surgery, Amsterdam University Medical Center, location AMC, Meibergdreef 9, Amsterdam, AZ 1105, Netherlands.

Background: Prolonged or excessive bleeding after cardiac surgery can lead to a broad spectrum of secondary complications. One of the underlying causes is incomplete wound drainage, with subsequent accumulation of blood and clots in the pericardium. We developed the continuous postoperative pericardial flushing (CPPF) therapy to improve wound drainage and reduce postoperative blood loss and bleeding-related complications after cardiac surgery. This study compared CPPF to standard care in patients after coronary artery bypass grafting (CABG).

Methods: This is a single center, open label, randomized trial that enrolled patients at the Amsterdam UMC, location AMC, Amsterdam, the Netherlands. The study was registered at the 'Netherlands Trial Register', study identifier NTR5200 [1]. Adults undergoing CABG were randomly assigned to receive CPPF therapy or standard care, participants and investigators were not masked to group assignment. The primary end point was postoperative blood loss in the first 12-hours after surgery.

Findings: Between the January 15, 2014 and the March 13, 2017, 169 patients were enrolled and assigned to CPPF therapy (study group;  = 83) or standard care (control group;  = 86). CPPF reduced postoperative blood loss when compared to standard care (median differences -385 ml, reduction 76% =≤0.001), with the remark that these results are overestimated due to a measurement error in part of the study group. None of patients in the study group required reoperation for non-surgical bleeding versus 3 (4%, 95% CI -0.4% to 7.0%) in the control group. None of the patients in the study group suffered from cardiac tamponade, versus 3 (4%, 95% CI -0,4% to 7.0%) in the control group. The incremental cost-effectiveness ratio was €116.513 (95% bootstrap CI €-882.068 to €+897.278).

Interpretation: The use of CPPF therapy after CABG seems to reduce bleeding and bleeding related complications. With comparable costs and no improvement in Qualty of Life (QoL), cost consideration for the implementation of CPPF is not relevant. None of the patients in the study group required re-interventions for non-surgical bleeding or acute cardiac tamponade, which underlines the proof of concept of this novel therapy.

Funding: This study was funded by ZonMw, the Netherlands organization for health research and development (project 837001405).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2020.100661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772543PMC
January 2021

Alkaline phosphatase in pulmonary inflammation-a translational study in ventilated critically ill patients and rats.

Intensive Care Med Exp 2020 Dec 18;8(Suppl 1):46. Epub 2020 Dec 18.

Department of Intensive Care, Amsterdam University Medical Centers, location "VU", Mail stop ZH 7D-172, De Boelelaan 1117, 1082 RW, Amsterdam, the Netherlands.

Background: Alkaline phosphatase (AP), a dephosphorylating enzyme, is involved in various physiological processes and has been shown to have anti-inflammatory effects.

Aim: To determine the correlation between pulmonary AP activity and markers of inflammation in invasively ventilated critically ill patients with or without acute respiratory distress syndrome (ARDS), and to investigate the effect of administration of recombinant AP on pulmonary inflammation in a well-established lung injury model in rats METHODS: AP activity was determined and compared with levels of various inflammatory mediators in bronchoalveolar lavage fluid (BALF) samples obtained from critically ill patients within 2 days of start of invasive ventilation. The endpoints of this part of the study were the correlations between AP activity and markers of inflammation, i.e., interleukin (IL)-6 levels in BALF. In RccHan Wistar rats, lung injury was induced by intravenous administration of 10 mg/kg lipopolysaccharide, followed by ventilation with a high tidal volume for 4 h. Rats received either an intravenous bolus of 1500 IU/kg recombinant AP or normal saline 2 h after intravenous LPS administration, right before start of ventilation. Endpoints of this part of the study were pulmonary levels of markers of inflammation, including IL-6, and markers of endothelial and epithelial dysfunction.

Results: BALF was collected from 83 patients; 10 patients had mild ARDS, and 15 had moderate to severe ARDS. AP activity correlated well with levels of IL-6 (r = 0.70), as well as with levels of other inflammatory mediators. Pulmonary AP activity between patients with and without ARDS was comparable (0.33 [0.14-1.20] vs 0.55 [0.21-1.42] U/L; p = 0.37). Animals with acute lung injury had markedly elevated pulmonary AP activity compared to healthy controls (2.58 [2.18-3.59] vs 1.01 [0.80-1.46] U/L; p < 0.01). Intravenous administration of recombinant AP did neither affect pulmonary inflammation nor endothelial and epithelial dysfunction.

Conclusions: In ventilated critically ill patients, pulmonary AP activity correlates well with markers of pulmonary inflammation, such as IL-6 and IL-8. In animals with lung injury, pulmonary AP activity is elevated. Administration of recombinant AP does not alter pulmonary inflammation and endothelial or epithelial dysfunction in the acute phase of a murine lung injury model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40635-020-00335-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746537PMC
December 2020

The effects of tidal volume size and driving pressure levels on pulmonary complement activation: an observational study in critically ill patients.

Intensive Care Med Exp 2020 Dec 18;8(Suppl 1):74. Epub 2020 Dec 18.

Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Background: Mechanical ventilation can induce or even worsen lung injury, at least in part via overdistension caused by too large volumes or too high pressures. The complement system has been suggested to play a causative role in ventilator-induced lung injury.

Aims And Methods: This was a single-center prospective study investigating associations between pulmonary levels of complement activation products and two ventilator settings, tidal volume (V) and driving pressure (ΔP), in critically ill patients under invasive ventilation. A miniature bronchoalveolar lavage (BAL) was performed for determination of pulmonary levels of C5a, C3b/c, and C4b/c. The primary endpoint was the correlation between BAL fluid (BALF) levels of C5a and V and ΔP. Levels of complement activation products were also compared between patients with and without ARDS or with and without pneumonia.

Results: Seventy-two patients were included. Median time from start of invasive ventilation till BAL was 27 [19 to 34] hours. Median V and ΔP before BAL were 6.7 [IQR 6.1 to 7.6] ml/kg predicted bodyweight (PBW) and 15 [IQR 11 to 18] cm HO, respectively. BALF levels of C5a, C3b/c and C4b/c were neither different between patients with or without ARDS, nor between patients with or without pneumonia. BALF levels of C5a, and also C3b/c and C4b/c, did not correlate with V and ΔP. Median BALF levels of C5a, C3b/c, and C4b/c, and the effects of V and ΔP on those levels, were not different between patients with or without ARDS, and in patients with or without pneumonia.

Conclusion: In this cohort of critically ill patients under invasive ventilation, pulmonary levels of complement activation products were independent of the size of V and the level of ΔP. The associations were not different for patients with ARDS or with pneumonia. Pulmonary complement activation does not seem to play a major role in VILI, and not even in lung injury per se, in critically ill patients under invasive ventilation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40635-020-00356-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746430PMC
December 2020

Therapeutic application of recombinant human ADAMTS-13 improves shock reversal and coagulation status in a trauma hemorrhage and transfusion rat model.

Intensive Care Med Exp 2020 Dec 18;8(Suppl 1):42. Epub 2020 Dec 18.

Department of Intensive Care Medicine, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands.

Introduction: In hemorrhaging trauma patients, the endothelium is activated, resulting in excessive endothelial synthesis of von Willebrand Factor (vWF), which may enhance micro-thrombi formation, resulting in obstruction of the microcirculation and endothelial injury, aggravating bleeding, as well as contributing to organ failure. Under normal conditions, vWF is cleaved by the metalloprotease ADAMTS-13. After trauma, ADAMTS-13 levels are reduced.

Objectives: To assess whether recombinant human ADAMTS-13 inhibits endothelial injury and organ failure in a rat trauma-transfusion model.

Methods: Blood products were prepared from syngeneic rat blood according to blood bank standards. Polytrauma was induced in rats by crush injury to the intestines and liver and by fracture of the femur. The rats were hemorrhaged until a mean arterial pressure (MAP) of 40 mmHg was reached. Rats were randomized to receive transfusion of RBCs, FFPs, and platelets in a 1:1:1 ratio to achieve a MAP of 70 mmHg, with or without the addition of ADAMTS-13 (50 μg/kg). Blood samples were assessed for biochemistry and rotational thromboelastometry (ROTEM). Syndecan-1 and VE-cadherin levels were measured as a reflection of endothelial integrity. The amount of leakage of dextran-FITC from the vascular system to the parenchyma in lungs was quantified. To assess inflammation, IL-6 and IL-8 levels were determined. Organ damage was assessed by histopathology.

Results: All rats were severely shocked, with no significant differences in shock parameters between groups. Rats treated with ADAMTS-13 showed signs of a more effective shock reversal (higher blood pressure, lower lactate levels) compared to controls. Also, ROTEM parameters of clot formation in rats receiving ADAMTS-13 improved compared to controls, which was mainly platelet-dependent. Syndecan-1 levels relative to baseline trended to be lower in ADAMTS-13 treated rats compared to controls (107 vs 149%, p = 0.08). ADAMTS-13 reduced albuminuria (1.7 vs 4.4 g/L, p < 0.01) and organ-specific inflammation (pulmonary IL-6 243 vs 369 pg/mL, p = 0.08; splenic IL-6 253 vs 307, p = 0.03) compared to controls, but did not improve histopathological scores.

Conclusions: The use of ADAMTS-13 in a rat trauma-transfusion model improves parameters of shock, platelet-driven coagulation, endothelial damage, and organ inflammation. These results suggest that ADAMTS-13 is important in mediating outcome of trauma. Whether ADAMTS-13 can be used as a therapeutic adjunct to treat bleeding trauma patients remains to be determined.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40635-020-00328-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746419PMC
December 2020

The predictive validity for mortality of the driving pressure and the mechanical power of ventilation.

Intensive Care Med Exp 2020 Dec 18;8(Suppl 1):60. Epub 2020 Dec 18.

Department of Intensive Care, University of Amsterdam, Amsterdam University Medical Centers, Location "Academic Medical Center", Meibergdreeg 9, 1105 AZ, Amsterdam, The Netherlands.

Background: Outcome prediction in critically ill patients under invasive ventilation remains extremely challenging. The driving pressure (ΔP) and the mechanical power of ventilation (MP) are associated with patient-centered outcomes like mortality and duration of ventilation. The objective of this study was to assess the predictive validity for mortality of the ΔP and the MP at 24 h after start of invasive ventilation.

Methods: This is a post hoc analysis of an observational study in intensive care unit patients, restricted to critically ill patients receiving invasive ventilation for at least 24 h. The two exposures of interest were the modified ΔP and the MP at 24 h after start of invasive ventilation. The primary outcome was 90-day mortality; secondary outcomes were ICU and hospital mortality. The predictive validity was measured as incremental 90-day mortality beyond that predicted by the Acute Physiology, Age and Chronic Health Evaluation (APACHE) IV score and the Simplified Acute Physiology Score (SAPS) II.

Results: The analysis included 839 patients with a 90-day mortality of 42%. The median modified ΔP at 24 h was 15 [interquartile range 12 to 19] cm HO; the median MP at 24 h was 206 [interquartile range 145 to 298] 10 J/min/kg predicted body weight (PBW). Both parameters were associated with 90-day mortality (odds ratio (OR) for 1 cm HO increase in the modified ΔP, 1.05 [95% confidence interval (CI) 1.03 to 1.08]; P < 0.001; OR for 100 10 J/min/kg PBW increase in the MP, 1.20 [95% CI 1.09 to 1.33]; P < 0.001). Area under the ROC for 90-day mortality of the modified ΔP and the MP were 0.70 [95% CI 0.66 to 0.74] and 0.69 [95% CI 0.65 to 0.73], which was neither different from that of the APACHE IV score nor that of the SAPS II.

Conclusions: In adult patients under invasive ventilation, the modified ΔP and the MP at 24 h are associated with 90 day mortality. Neither the modified ΔP nor the MP at 24 h has predictive validity beyond the APACHE IV score and the SAPS II.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40635-020-00346-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746416PMC
December 2020

Mechanical ventilation of the healthy lungs: lessons learned from recent trials.

Curr Opin Crit Care 2021 02;27(1):55-59

Department of Intensive Care.

Purpose Of Review: Although there is clear evidence for benefit of protective ventilation settings [including low tidal volume and higher positive end-expiratory pressure (PEEP)] in patients with acute respiratory distress syndrome (ARDS), it is less clear what the optimal mechanical ventilation settings are for patients with healthy lungs.

Recent Findings: Use of low tidal volume during operative ventilation decreases postoperative pulmonary complications (PPC). In the critically ill patients with healthy lungs, use of low tidal volume is as effective as intermediate tidal volume. Use of higher PEEP during operative ventilation does not decrease PPCs, whereas hypotension occurred more often compared with use of lower PEEP. In the critically ill patients with healthy lungs, there are conflicting data regarding the use of a higher PEEP, which may depend on recruitability of lung parts. There are limited data suggesting that higher driving pressures because of higher PEEP contribute to PPCs. Lastly, use of hyperoxia does not consistently decrease postoperative infections, whereas it seems to increase PPCs compared with conservative oxygen strategies.

Summary: In patients with healthy lungs, data indicate that low tidal volume but not higher PEEP is beneficial. Thereby, ventilation strategies differ from those in ARDS patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCC.0000000000000787DOI Listing
February 2021

Targeting Endothelial Dysfunction in Acute Critical Illness to Reduce Organ Failure.

Anesth Analg 2020 12;131(6):1708-1720

Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

During hyperinflammatory conditions that can occur in acute critical illness, such as shock or hypoperfusion, inflammatory mediators activate the endothelium, fueling a proinflammatory host-response as well as procoagulant processes. These changes result in shedding of the glycocalyx, endothelial hyperpermeability, edema formation, and lead to disturbed microcirculatory perfusion and organ failure. Different fluid strategies that are used in shock may have differential effects on endothelial integrity. Collectively, low protein content fluids seem to have negative effects on the endothelial glycocalyx, aggravating endothelial hyperpermeability, whereas fluids containing albumin or plasma proteins may be superior to normal saline in protecting the glycocalyx and endothelial barrier function. Targeting the endothelium may be a therapeutic strategy to limit organ failure, which hitherto has not received much attention. Treatment targets aimed at restoring the endothelium should focus on maintaining glycocalyx function and/or targeting coagulation pathways or specific endothelial receptors. Potential treatments could be supplementing glycocalyx constituents or inhibiting glycocalyx breakdown. In this review, we summarize mechanisms of endothelial dysfunction during acute critical illness, such as the systemic inflammatory response, shedding of the glycocalyx, endothelial activation, and activation of coagulation. In addition, this review focuses on the effects of different fluid strategies on endothelial permeability. Also, potential mechanisms for treatment options to reduce endothelial hyperpermeability with ensuing organ failure are evaluated. Future research is needed to elucidate these pathways and to translate these data to the first human safety and feasibility trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1213/ANE.0000000000005023DOI Listing
December 2020

Transfusion in the mechanically ventilated patient.

Intensive Care Med 2020 12 12;46(12):2450-2457. Epub 2020 Nov 12.

Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium.

Red blood cell transfusions are a frequent intervention in critically ill patients, including in those who are receiving mechanical ventilation. Both these interventions can impact negatively on lung function with risks of transfusion-related acute lung injury (TRALI) and other forms of acute respiratory distress syndrome (ARDS). The interactions between transfusion, mechanical ventilation, TRALI and ARDS are complex and other patient-related (e.g., presence of sepsis or shock, disease severity, and hypervolemia) or blood product-related (e.g., presence of antibodies or biologically active mediators) factors also play a role. We propose several strategies targeted at these factors that may help limit the risks of associated lung injury in critically ill patients being considered for transfusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00134-020-06303-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658306PMC
December 2020

Mechanical ventilation in patients with acute brain injury: recommendations of the European Society of Intensive Care Medicine consensus.

Intensive Care Med 2020 12 11;46(12):2397-2410. Epub 2020 Nov 11.

School of Medicine and Surgery, University of Milano - Bicocca, Milan, Italy.

Purpose: To provide clinical practice recommendations and generate a research agenda on mechanical ventilation and respiratory support in patients with acute brain injury (ABI).

Methods: An international consensus panel was convened including 29 clinician-scientists in intensive care medicine with expertise in acute respiratory failure, neurointensive care, or both, and two non-voting methodologists. The panel was divided into seven subgroups, each addressing a predefined clinical practice domain relevant to patients admitted to the intensive care unit (ICU) with ABI, defined as acute traumatic brain or cerebrovascular injury. The panel conducted systematic searches and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to evaluate evidence and formulate questions. A modified Delphi process was implemented with four rounds of voting in which panellists were asked to respond to questions (rounds 1-3) and then recommendation statements (final round). Strong recommendation, weak recommendation, or no recommendation were defined when > 85%, 75-85%, and < 75% of panellists, respectively, agreed with a statement.

Results: The GRADE rating was low, very low, or absent across domains. The consensus produced 36 statements (19 strong recommendations, 6 weak recommendations, 11 no recommendation) regarding airway management, non-invasive respiratory support, strategies for mechanical ventilation, rescue interventions for respiratory failure, ventilator liberation, and tracheostomy in brain-injured patients. Several knowledge gaps were identified to inform future research efforts.

Conclusions: This consensus provides guidance for the care of patients admitted to the ICU with ABI. Evidence was generally insufficient or lacking, and research is needed to demonstrate the feasibility, safety, and efficacy of different management approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00134-020-06283-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655906PMC
December 2020

Fill the critical care discovery pipeline with ICMx!

Intensive Care Med Exp 2020 Nov 9;8(1):65. Epub 2020 Nov 9.

Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Trauma Research Center, Vienna, Austria.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40635-020-00355-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652981PMC
November 2020
-->