Intravenous enoxaparin as alternative ECMO anticoagulation over a period of 94 days: a case report.

BACKGROUND: Unfractionated heparin is used worldwide as a standard anticoagulation therapy for extracorporeal membrane oxygenation (ECMO) machines. However, its use brings about significant bleeding and thrombotic complications for critically ill patients. This case report shows that low molecular weight heparin together with ECMO-produced primary haemostasis pathology can be used as an alternative way of ECMO anticoagulation. CASE PRESENTATION: This paper presents the case of a patient with respiratory failure who subsequently suffered from cardiac failure and spent 94 days on combined V-V and V-A ECMO devices (two ECMO devices running simultaneously on one patient) with intravenous enoxaparin used instead of unfractionated heparin anticoagulation. No life-threatening bleeding/thrombotic events happened during this period, nor did any technical problems with ECMO occur. CONCLUSIONS: In this case report, continuous intravenous low molecular weight heparin anticoagulation was used as a safe alternative to ECMO anticoagulation.

Effect of targeted coagulopathy management and 5% albumin as volume replacement therapy during lung transplantation on allograft function: a secondary analysis of a randomized clinical trial.

BACKGROUND: Primary graft dysfunction (PGD) after lung transplantation (LuTx) contributes substantially to early postoperative morbidity. Both intraoperative transfusion of a large amount of blood products during the surgery and ischemia-reperfusion injury after allograft implantation play an important role in subsequent PGD development. METHODS: We have previously reported a randomized clinical trial of 67 patients where point of care (POC) targeted coagulopathy management and intraoperative administration of 5% albumin led to significant reduction of blood loss and blood product consumption during the lung transplantation surgery. A secondary analysis of the randomized clinical trial evaluating the effect of targeted coagulopathy management and intraoperative administration of 5% albumin on early lung allograft function after LuTx and 1-year survival was performed. RESULTS: Compared to the patients in the control (non-POC) group, those in study (POC) group showed significantly superior graft function, represented by the Horowitz index (at 72 h after transplantation 402.87 vs 308.03 with p < 0.001, difference between means: 94.84, 95% CI: 60.18-129.51). Furthermore, the maximum doses of norepinephrine administered during first 24 h were significantly lower in the POC group (0.193 vs 0.379 with p < 0.001, difference between the means: 0.186, 95% CI: 0.105-0.267). After dichotomization of PGD (0-1 vs 2-3), significant difference between the non-POC and POC group occurred only at time point 72, when PGD grade 2-3 developed in 25% (n = 9) and 3.2% (n = 1), respectively (p = 0.003). The difference in 1-year survival was not statistically significant (10 patients died in non-POC group vs. 4 patients died in POC group; p = 0.17). CONCLUSIONS: Utilization of a POC targeted coagulopathy management combined with Albumin 5% as primary resuscitative fluid may improve early lung allograft function, provide better circulatory stability during the early post-operative period, and have potential to decrease the incidence of PGD without negative effect on 1-year survival. TRIAL REGISTRATION: This clinical trial was registered at ClinicalTrials.gov (NCT03598907).

Factors Affecting the Metabolic Conversion of Ciprofloxacin and Exposure to Its Main Active Metabolites in Critically Ill Patients: Population Pharmacokinetic Analysis of Desethylene Ciprofloxacin.

The objective of this prospective study was to examine the exposure to the main active metabolites of ciprofloxacin in critically ill patients and to examine the factors (demographic, laboratory and genetic) that could potentially affect the drug metabolic conversion of ciprofloxacin. The secondary aim was to develop a population pharmacokinetic model for the metabolite showing the most associations with the abovementioned factors. A total of 29 patients were treated with intravenous infusion of ciprofloxacin and enrolled on this trial. Blood samples for pharmacokinetic analysis were taken at 1, 4, and 11.5 h following the completion of the infusion. Sex, age, body weight, height, serum creatinine and bilirubin levels, and creatinine clearance (CLCR) were recorded, and polymorphisms rs2032582 and rs1045642 in the ABCB1 gene, rs4148977 in the SLCO1A2 gene and rs762551 in the CYP1A2 gene were analyzed. A three-stage parent drug-metabolite population pharmacokinetic model was developed. Median (IQR) metabolite/parent ratios of the desethylene ciprofloxacin, formyl ciprofloxacin and oxociprofloxacin were 5.86 (4.09-9.87)%, 4.08 (3.38-6.92)% and 5.91 (3.42-13.65)%, respectively. The desethylene ciprofloxacin metabolic ratio was positively associated with height (r2 = 0.2277, p = 0.0089) and CLCR (r2 = 0.2023, p = 0.0144) and negatively associated with age (r2 = 0.2227, p = 0.0112). Males had a significantly higher oxociprofloxacin metabolic ratio than females (9.14 vs 3.42%, p = 0.0043). In the desethylene ciprofloxacin population PK model, the volume of distribution decreased with age, the parent drug-metabolite transfer rate constant increased with CLCR, and the metabolite elimination rate constant decreased with age and is increased in CYP1A2 rs762551 variant allele carriers. We therefore hypothesized that the CYP1A2 inhibition by ciprofloxacin is mediated by its metabolite desethylene ciprofloxacin.

No Time Dependence of Ciprofloxacin Pharmacokinetics in Critically Ill Adults: Comparison of Individual and Population Analyses.

The aim of this prospective PK study was to evaluate the pharmacokinetics of ciprofloxacin dosed within the first 36 h (early phase) and after 3 days of treatment (delayed phase) using individual and population PK analysis. The secondary aim of the study was to evaluate possible dosing implications of the observed PK differences between early and delayed phases to achieve a PK/PD target for ciprofloxacin of AUC24/MIC ≥ 125. Blood concentrations of ciprofloxacin (1 and 4 h after dose and trough) were monitored in critically ill adults in the early and delayed phases of the treatment. Individual and population PK analyses were performed. Complete concentration-time profiles in the early phase, delayed phase, and both phases were obtained from 29, 15, and 14 patients, respectively. No systematic changes in ciprofloxacin PK parameters between the early and delayed phases were observed, although variability was higher at the early phase. Both individual and population analyses provided similar results. Simulations showed that after standard dosing, it is practically impossible to reach the recommended ciprofloxacin PK/PD target (AUC/MIC ≥ 125) for pathogens with MIC ≥ 0.5 mg/L. A dosing nomogram utilizing patients' creatinine clearance and MIC values was constructed. Both individual and population analyses provided similar results. Therapeutic drug monitoring should be implemented to safeguard the optimal ciprofloxacin exposure.

Direct detection of ESKAPEc pathogens from whole blood using the T2Bacteria Panel allows early antimicrobial stewardship intervention in patients with sepsis.

In the microbiological diagnosis of bloodstream infections (BSI), blood culture (BC) is considered the gold standard test despite its limitations such as low sensitivity and slow turnaround time. A new FDA-cleared and CE-marked platform utilizing magnetic resonance to detect amplified DNA of the six most common and/or problematic BSI pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli; referred to as ESKAPEc) is available and may shorten the time to diagnosis and potentially improve antimicrobial utilization. Whole blood samples from hospitalized patients with clinical signs of sepsis were analyzed using the T2Bacteria Panel (T2Biosystems) and compared to simultaneously collected BC. Discrepant results were evaluated based on clinical infection criteria, combining supporting culture results and the opinion of treating physicians. A total of 55 samples from 53 patients were evaluated. The sensitivity and specificity of the T2Bacteria panel was 94% (16 out of 17 detections of T2Bacteria-targeted organisms) and 100%, respectively, with 36.4% (8 of 22) causes of BSI detected only by this method. The T2Bacteria Panel detected pathogens on average 55 hours faster than standard BC. In our study, 9 of 15 patients with positive T2Bacteria Panel results received early-targeted antibiotic therapy and/or modification of antimicrobial treatment based on T2Bacteria Panel findings. Given the high reliability, faster time to detection, and easy workflow, the technique qualifies as a point-of-care testing approach.

Rotational thromboelastometry reduces blood loss and blood product usage after lung transplantation.

BACKGROUND: The shortage of blood products has become a worldwide problem, especially during the COVID-19 Pandemic. Here, we investigated whether a point of care (POC) approach to perioperative bleeding and coagulopathy based on rotational thromboelastometry (ROTEM) results could decrease perioperative blood loss and the perioperative consumption of blood products during lung transplantation. METHODS: Patients undergoing bilateral lung transplantation were randomized into two groups: In the first group, designated the "non POC" group, the management of perioperative bleeding and coagulopathy was based on the clinical experience of the anesthesiologist; in the second group, designated the "POC" group, the management of perioperative bleeding, and coagulopathy was based on the ROTEM results. RESULTS: After performing an interim statistical analysis, the project was prematurely terminated as the results were significantly in favor of the POC approach. Data were analyzed for the period January 2018 until June 2020 when 67 patients were recruited into the study. There was significantly decreased perioperative blood loss in the POC group (n = 31 patients) with p = 0.013, decreased perioperative consumption of RBC with p = 0.009, and decreased perioperative consumption of fresh frozen plasma with p < 0.0001 (practically no fresh frozen plasma was used in the POC group) without deteriorating clot formation in secondary and primary hemostasis as compared to the non POC group (n = 36). CONCLUSION: POC management of perioperative bleeding and coagulopathy based on ROTEM results is a promising strategy to decrease perioperative blood loss and the consumption of blood products in lung transplantation.

COVID-19 severe pneumonia: Prospective multicentre study on demands on intensive care capacities.

OBJECTIVES: The aim of the study was to obtain data on demands on the intensive care capacities to treat COVID-19 patients, and to identify predictors for in-hospital mortality. METHODS: The prospective observational multicentre study carried out from 1 March till 30 June 2020 included adult patients with confirmed SARS-CoV-2 infection with respiratory failure requiring ventilatory support or high-flow nasal oxygen therapy (HFNO). RESULTS: Seventy-four patients, 46 males and 28 females, median age 67.5 (Q1-Q3: 56-75) years, were included. Sixty-four patients (86.5%) had comorbidity. Sixty-six patients (89.2%) were mechanically ventilated, four of them received extracorporeal membrane oxygenation therapy. Eight patients (10.8%) were treated with non-invasive ventilation and HFNO only. The median of intensive care unit (ICU) stay was 22.5 days. Eighteen patients (24.3%) needed continuous renal replacement therapy. Thirty patients (40.5%) died. Age and acute kidney injury were identified as independent predictors of in-hospital death, and chronic kidney disease showed trend towards statistical significance for poor outcome. CONCLUSIONS: Sufficient number of intensive care beds, organ support equipment and well-trained staff is a decisive factor in managing the COVID-19 epidemic. The study focused on the needs of intensive care in the COVID-19 patients. Advanced age and acute kidney injury were identified as independent predictors for in-hospital mortality. When compared to clinical course and ICU management of patients with severe community-acquired pneumonia caused by other pathogens, we observed prolonged need for ventilatory support, high rate of progression to acute respiratory distress syndrome and significant mortality in studied population.

Limited diagnostic possibilities for bloodstream infections with broad-range methods: A promising PCR/electrospray ionization-mass spectrometry platform is no longer available.

Fast and accurate detection of causative agents of bloodstream infections remains a challenge of today's microbiology. We compared the performance of cutting-edge technology based on polymerase chain reaction coupled with electrospray ionization-mass spectrometry (PCR/ESI-MS) with that of conventional broad-range 16S rRNA PCR and blood culture to address the current diagnostic possibilities for bloodstream infections. Of 160 blood samples tested, PCR/ESI-MS revealed clinically meaningful microbiological agents in 47 samples that were missed by conventional diagnostic approaches (29.4% of all analyzed samples). Notably, PCR/ESI-MS shortened the time to positivity of the blood culture-positive samples by an average of 34 hr. PCR/ESI-MS technology substantially improved current diagnostic tools and represented an opportunity to make bloodstream infections diagnostics sensitive, accurate, and timely with a broad spectrum of microorganisms covered.

Extracorporeal membrane oxygenation-induced fibrinolysis detected by rotational thromboelastometry and treated by oxygenator exchange.

Coagulopathy and bleeding is a frequent phenomenon in patients on extracorporeal membrane oxygenation. The cause may be multifactorial and it may change over time. We present a case when bleeding was caused by hyperfibrinolysis induced by oxygenator. The diagnosis was established by comparing thromboelastometry result from blood obtained before and after oxygenator. Hyperfibrinolysis and bleeding could be successfully treated merely by oxygenator exchange.

Direct thrombolysis of multiple thrombi in both right and left heart atrium in a patient on extracorporeal membrane oxygenation support following urgent double-lung transplantation: a case report.

BACKGROUND: Lung transplantation is considered an established treatment for patients with end-stage chronic respiratory failure. Patients with acute respiratory failure requiring respiratory support with invasive mechanical ventilation while awaiting lung transplantation are at high risk of death. Extracorporeal membrane oxygenation (ECMO) has been proposed as an alternative bridging strategy to mechanical ventilation. The shear stress created by the mechanical pumps causes changes in the hematological system in almost all patients treated with ECMO. An antithrombotic strategy to mitigate ECMO bleeding and thrombotic complications is necessary. The use of thrombolytic therapy is recommended for patients with acute symptomatic embolism with associated hypotension or shock. In this setting, the hemodynamic benefits of thrombolytic treatment far outweigh its bleeding risk. CASE PRESENTATION: This case report describes a 32-year-old woman suffering from lymphangioleiomyomatosis, who underwent urgent double-lung transplantation. This patient was maintained on ECMO preoperatively, perioperatively, and postoperatively due to life-threatening hypoxemia caused by the progression of her pulmonary tissue damage. Multiple thrombi developed in the early postoperative period, in both right and left heart atria. Direct thrombolysis was successfully performed on the first postoperative day. CONCLUSION: According to the current published literature, direct thrombolysis of thrombi in both right and left atria in a patient supported on ECMO following urgent double-lung transplantation is an extremely rare treatment method. Even when taking into account all of the risks associated with thrombolysis and arteriovenous ECMO support, we found that this technique is very effective and, without a doubt, it saved the life of our patient.

Tracheostomy in intensive care unit patients can be performed without bleeding complications in case of normal thromboelastometry results (EXTEM CT) despite increased PT-INR: a prospective pilot study.

BACKGROUND: Coagulopathy is often accompanied by prolongation of prothrombin time (PT) in septic and nonseptic patients in intensive care unit (ICU). The conventional way to correct the coagulopathy is to administer fresh frozen plasma (FFP) before invasive procedures to minimise the risk of bleeding. However, prolonged PT can be present even in hypercoagulation status, resulting in unnecessary administration of FFP. In the present study, we have assessed the reliability of thromboelastometry in case of prolonged PT and the relationship to bleeding complications during surgical tracheostomy. METHODS: The study was conducted during the period between April 2013 and April 2014 in patients undergoing surgical tracheostomy. Coagulation status was assessed using PT, and the status was reassessed by thromboelastometry for prolonged PT. Tracheostomy was performed in patients with normal thromboelastometry results without administering FFP. RESULTS: Tracheostomy was performed in total 119 patients. Normal value of PT as measured by international normalized ratio (INR) ≤ 1.2 was found in 64 (54%) patients, while prolonged INR > 1.2 was found in 55 (46%) patients. Patients with INR ≥ 1.3 (with INR min- 1.3, max- 1.84, and median- 1.48) were further analysed by thromboelastometry. Despite prolonged INR, thromboelastometry results were in normal ranges in all cases except one. With normal thromboelastometry, tracheostomy was performed safely without any bleeding complication. CONCLUSIONS: Surgical tracheostomy in septic and nonseptic patients can be performed without bleeding complications in case of normal thromboelastometry results (EXTEM CT) despite increased PT-INR. This method can help physicians to reduce unnecessary administration of FFP in patients.