Prognostic significance of early acute kidney injury in COVID-19 patients requiring mechanical ventilation: a single-center retrospective analysis.

Acute kidney injury (AKI) is associated with impaired outcomes in critically ill COVID-19 patients. However, the prognostic significance of early AKI is poorly described. We aimed to determine whether AKI on admission to the intensive care unit (ICU) and its development within the first 48 h predict the need for renal replacement therapy (RRT) and increased mortality. An analysis of 372 patients with COVID-19 pneumonia requiring mechanical ventilation without advanced chronic kidney disease from 2020 to 2021 was performed. The AKI stages on ICU admission and Day 2 were determined using adapted KDIGO criteria. The early development of renal function was assessed by the change in AKI score and the Day-2/Day-0 creatinine ratio. Data were compared between three consecutive COVID-19 waves and with data before the pandemic. Both ICU and 90-day mortality (79% and 93% vs. 35% and 44%) and the need for RRT increased markedly with advanced AKI stage on ICU admission. Similarly, an early increase in AKI stage and creatinine implied highly increased mortality. RRT was associated with very high ICU and 90-day mortality (72% and 85%), even surpassing that of patients on ECMO. No difference was found between consecutive COVID-19 waves, except for a lower mortality in the patients on RRT in the last omicron wave. Mortality and need for RRT were comparable in the COVID-19 and pre-COVID-19 patients, except that RRT did not increase ICU mortality in the pre-COVID-19 era. In conclusion, we confirmed the prognostic significance of both AKI on ICU admission and its early development in patients with severe COVID-19 pneumonia.

Differences in monocyte subsets are associated with short-term survival in patients with septic shock.

Sepsis is characterized by dynamic changes of the immune system resulting in deregulated inflammation and failure of homoeostasis and can escalate to septic shock. Circulating monocytes and other innate immune cells are among the first ones to recognize and clear pathogens. Monocytes have an important role in sepsis and septic shock and have been studied as potential diagnostic markers. In total, forty-two patients with septic shock were recruited and blood samples obtained within first 12 hours of ICU admission. We showed that frequency of classical and intermediate monocytes assessed at the time of admission to the intensive care unit are significantly distinct in patients with septic shock who survived longer that five days from those who died. These parameters correlate significantly with differences in serum levels of inflammatory cytokines MCP-1, IL-6, IL-8, IL-10, and IL-18, and with the proportion of helper and cytotoxic T cells. The described changes in frequency of monocyte subsets and their activation status may predict short-term septic shock survival and help with fast identification of the group of vulnerable patients, who may profit from tailored therapy.

Pharmacokinetic Comparison of Subcutaneous and Intravenous Nadroparin Administration for Thromboprophylaxis in Critically Ill Patients on Vasopressors.

INTRODUCTION: Critically ill patients are exposed to a high risk of developing thromboembolism. Moreover, standard prophylaxis with subcutaneous (SC) heparin is less efficient in patients requiring vasopressors. The aim is a comparison of pharmacokinetics between SC and intravenous (IV) applied nadroparin. METHODS: Thirty-eight ventilated ICU patients requiring vasopressor support were randomized into a single dose of nadroparin 3,800 IU (0.4 mL) subcutaneously (SC group) or 1,900 IU (0.2 mL) intravenously (IV group). Anti-factor Xa activity (anti-Xa) was observed over 24 h; data are stated as median (IQR). RESULTS: Peak anti-Xa was significantly higher in the IV group 0.42 (0.39-0.43) IU/mL than in the SC group 0.16 (0.09-0.18) IU/mL (p < 0.001). There was a trend towards higher area under the curve (AUC) of anti-Xa in the SC group 1.41 (0.41-1.80) IU/mL × h than in the IV group 1.04 (0.93-1.13) IU/mL × h (p = 0.08). In the SC group, there was a negative correlation between anti-Xa AUC and both capillary refill time Xa (r = -0.86) and norepinephrine dose (r = -0.68). In the IV group, anti-Xa decrease half-life was 1.6 (1.4-2.0) h. CONCLUSIONS: IV administration of 1,900 IU of nadroparin led to a predictable effective peak anti-Xa. After SC administration, anti-Xa was heterogeneous and significantly influenced by peripheral perfusion.

Comparison of Active Substance Losses and Total Weight Losses of Tablets Administered Via Feeding Tube.

BACKGROUND/AIMS: Administration of tablets via feeding tube (FT) is often associated with significant drug losses, as was confirmed by weighing. The aim of this study was to measure the proportion of active substance losses (ASLs) in an in vitro model. METHODS: A film-coated tablet (FilmCT) containing clopidogrel (Trombex®) and a tablet with enteric coating (EntericCT) containing pantoprazole (Controloc®) were crushed in a mortar and transferred by method A (tablet powder was transferred into the beaker, poured into the syringe and water added) and method B (water was added into the mortar, suspension drawn into the syringe) and administered via FT in an in vitro model. Total losses were measured with analytical balance and, simultaneously, ASL were analyzed with high-performance liquid chromatography UV-detection (HPLC-UV). RESULTS: ASL was different to weighing only in the case of EntericCT prepared by method B (2.0 ± 4.2 and 10.7 ± 0.8% for HPLC-UV and weighing, respectively; p = 0.004). HPLC-UV confirmed significantly lower ASL when method B was used for either EntericCT (34.3 ± 7.2 vs. 2.0 ± 4.2%; p < 0.001) or FilmCT (14.1 ± 2.2 vs. 7.7 ± 4.1%; p < 0.01). CONCLUSION: Drug loss analysis with analytical balance may overestimate ASL, as was proved for EntericCT in this study. ASL were significantly lower when method B was used.

The impact of sedation on pulse pressure variation.

OBJECTIVE: Pulse pressure variations (PPV) are mainly influenced by ventilation. The impact of sedation on PPV is not known. The aim of the study was to test the influence of sedation on pulse pressure variation in mechanically ventilated critically ill patients and to compare PPV in critically ill and brain dead patients. Beside the absolute value of PPV, the adjusted values of pulse pressure were used to eliminate influence of ventilation. DESIGN AND INTERVENTION: Mechanically ventilated patients received four different breath frequencies. At each frequency airway pressure was adjusted to keep the end-tidal CO2 stable. In critically ill patients the frequencies were applied at basal (bispectral index - BIS median 38) and deeper sedation (BIS 29). MAIN OUTCOME MEASURES: Simultaneous haemodynamic and respiratory data including oesophageal pressure were recorded, adjusted PPV were calculated as PPV/VT, PPV/dPair, PPV/dPes where VT is tidal volume, dPair and dPes are airway and oesophageal driving pressures. SETTING: University Hospital, ICU. PARTICIPANTS: 30 critically ill and 23 patients with a diagnosis of brain death. RESULTS: The pulse pressure variation did not change significantly during deep sedation compared to basal sedation (median 10.3 vs 10.9%) whereas PPV/dPair increased from 0.7 to 0.8%/cmH2O and PPV/dPes from 1.9%/cmH2O to 2.4%/cmH2O (p=0.04). Patients with a diagnosis of brain death had higher PPV and adjusted PPV than critically ill patients. CONCLUSION: Deeper sedation increases values of adjusted pulse pressure variation.

Temperature corrected thromboelastography in hypothermia: is it necessary?

CONTEXT: Hypothermia is known to influence thromboelastography (TEG). TEG reproducibility is generally low. OBJECTIVE: The aim of this study was to evaluate the rationale of TEG temperature adjustment in patients during hypothermia. We hypothesised that temperature adjustment would not be important because of low TEG reproducibility. DESIGN: Prospective observational study. SETTING: Single-centre, secondary care study performed 01/2009 to 07/2010. PATIENTS: Survivors of cardiopulmonary resuscitation in whom therapeutic hypothermia (32 to 34°C) was indicated for 24 h were recruited to the study which lasted 36 h. Four hundred samples from 30 patients (22 men and eight women) were obtained. No specific exclusion criteria were defined. MAIN OUTCOME MEASURES: Temperature adjusted and non-adjusted Kaolin-Heparinase and Rapid-TEG were done at 12-h intervals during the first 36 h. RESULTS: Bland-Altman plots were used for analysis. During hypothermia, the bias of adjusted measurements was greater in clot formation variables for both Kaolin-Heparinase-TEG (from -15 to -19%) and Rapid-TEG (-9 to -25%) compared to normothermia (from -3 to 3% for Kaolin-Heparinase-TEG and -10 to 2% for Rapid-TEG). Bias of clot strength variables was not influenced by temperature adjustment (median -1%). The 95% limits of agreement were wide for clot formation variables and independent of temperature. In Kaolin-Heparinase-TEG (R -42 to 40% normothermia, -47 to 18% hypothermia) and in Rapid-TEG (R -117 to 97% normothermia, -114 to 95% hypothermia). Limits of agreement of clot strength variables were narrower and independent of temperature in Kaolin-Heparinase-TEG (MA -16 to 13% normothermia, -9 to 10% hypothermia) and also in Rapid-TEG (MA -27 to 24% normothermia, -18 to 20% hypothermia). CONCLUSION: Although TEG analysis with temperature adjusted to the in-vivo value during hypothermia yields results with small systematic bias, the importance of temperature adjustment in clinical routine is low because of the precision limits of TEG measurement itself. Therefore, we see no need to perform TEG analysis at the in-vivo temperature.

Use of fondaparinux in patients with heparin-induced thrombocytopenia on veno-venous extracorporeal membrane oxygenation: A three-patient case series report.

Heparin-induced thrombocytopenia is a life-threatening immune-mediated complication of unfractionated heparin therapy. Fondaparinux is a therapeutic alternative, but it has limited evidence for its use in patients on extracorporeal membrane oxygenation (ECMO). We present a series of three adult patients with COVID-19 on ECMO who were diagnosed with heparin-induced thrombocytopenia after 7-12 days of unfractionated heparin treatment and were switched to fondaparinux. Fondaparinux was initiated with an intravenous loading dose of 5 mg, followed by a dose of 2.5 mg subcutaneously every 8-12 h. Dosage was adjusted according to daily measured anti-Xa concentration with a target range of 0.4-0.7 mg/L. The total duration of treatment with fondaparinux and ECMO ranged from 13 to 26 days. One major bleeding episode unrelated to fondaparinux therapy was observed, and the transfusions requirement was also low in all patients. The ECMO circuit was changed once in each patient. This series provides a deep insight into the use of fondaparinux over an extended period of time in patients on ECMO. Based on the presented data, fondaparinux can be considered a reasonable and affordable anticoagulant in patients without a high risk of bleeding.

Challenges of Colistin Use in ICU and Therapeutic Drug Monitoring: A Literature Review.

The emerging resistance of Gram-negative bacteria is a growing problem worldwide. Together with the financial cost, limited efficacy, and local unavailability of newer antibiotics or their combinations, it has led to the reintroduction of colistin as a therapeutic alternative. Despite its protracted development and availability on the market, there is now a complex maze of questions surrounding colistin with a more or less straightforward relationship to its safety and efficacy. This review aims to offer a way to navigate this maze. We focus on summarizing the available literature regarding the use of colistin in critically ill patients, particularly on stability, pharmacokinetics, methods for determining plasma concentrations, and therapeutic drug monitoring benefits and limitations. Based on these data, we then highlight the main gaps in the available information and help define directions for future research on this drug. The first gap is the lack of data on the stability of intravenous and nebulization solutions at clinically relevant concentrations and under external conditions corresponding to clinical practice. Furthermore, pharmacokinetic-pharmacodynamic parameters should be validated using standardized dosing, including a loading dose. Based on the pharmacokinetic data obtained, a population model for critically ill patients should be developed. Finally, the interference of colistin with extracorporeal methods should be quantified.

Changes of colistin pharmacokinetics in critically ill patients due to the extracorporeal membrane oxygenation: protocol for the COL-ECMO2022 trial - a prospective, non-randomised, open-label phase IV pharmacokinetic clinical trial.

INTRODUCTION: Colistin is a lipopeptide antibiotic administered as an inactive prodrug-colistin methanesulfonate (CMS). Colistin is a drug with a narrow therapeutic window; the limiting factors are mainly nephrotoxicity and neurotoxicity, dependent on plasma concentrations. The number of patients with infections caused by multidrug-resistant Gram-negative bacteria sensitive only to colistin and the number of patients requiring extracorporeal membrane oxygenation (ECMO) support for severe respiratory failure increased significantly in association with COVID-19-induced infections. ECMO can generally affect the pharmacokinetics of drugs by creating a new compartment. METHODS AND ANALYSIS: The COL-ECMO2022 study is a prospective, non-randomised, single-centre, phase IV pharmacokinetic clinical trial designed to assess the influence of ECMO on the pharmacokinetics of colistin and CMS. Up to 30 patients treated with colistin will be included in the study and assigned to one of two arms, depending on the presence/absence of ECMO. All study participants will receive standard CMS dose intravenously. The plasma concentrations of colistin and CMS taken at defined intervals will be assessed by high-performance liquid chromatography-mass spectrometry. Patients will participate in the clinical trial for a maximum of three monitored dosing intervals. A population pharmacokinetic model will be developed to assess the influence of ECMO on pharmacokinetics. A difference greater than 25% is considered clinically significant. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of St. Anne's University Hospital Brno (Number 10ML/2022-AM). Related manuscripts will be submitted to peer-review journals. TRIAL REGISTRATION NUMBERS: EudraCT Number 2022-000291-19; NCT05542446.

Extracorporeal Membrane Oxygenation Use in Thoracic Surgery.

This narrative review is focused on the application of extracorporeal membrane oxygenation (ECMO) in thoracic surgery, exclusive of lung transplantation. Although the use of ECMO in this indication is still rare, it allows surgery to be performed in patients where conventional ventilation is not feasible-especially in single lung patients, sleeve lobectomy or pneumonectomy and tracheal or carinal reconstructions. Comparisons with other techniques, various ECMO configurations, the management of anticoagulation, anesthesia, hypoxemia during surgery and the use of ECMO in case of postoperative respiratory failure are reviewed and supported by two cases of perioperative ECMO use, and an overview of published case series.

Characterisation of neutron field in the polyethylene neutron irradiator.

The paper describes neutron field characterisation of low-flux multipurpose educational irradiator developed at Czech Technical University in Prague. The irradiator is aimed for demonstration experiments including neutron activation analysis, delayed neutron counting, or studies related to neutron and/or gamma detection and spectrometric devices. It may accommodate various neutron sources including 252Cf or AmBe radionuclide sources, D-D generator, or in-reactor irradiated nuclear material serving as delayed neutron source, or gamma sources including radionuclide ones or short-lived sources produced in the adjacent reactor. The characterisation was performed based on neutron activation technique using gold foils. It included two experimental parts. The first one verified the level of response symmetry in the four irradiation channels and characterisation of the axial distribution in the irradiation channels. Within the second one, the responses to thermal and epithermal neutrons and the cadmium ratio in the central irradiation position were determined. Whereas the former was determined solely with the 252Cf source, the latter was performed for all available sources: 252Cf, AmBe, and the D-D generator. The experimental results were further compared to calculations by the MCNP Monte Carlo code.

Ischaemic Stroke Caused by a Gunshot Wound to the Chest.

INTRODUCTION: Pneumatic weapons rarely cause severe trauma. However, pellet embolisation can cause severe and unexpected injuries. REPORT: This is the case study of a 32 year old man, who was shot in the chest with a pneumatic rifle. Initially, urgent damage control surgery was performed to resolve pneumothorax and pericardial tamponade, but no projectile was found. Subsequent atypical symptomatology led to more extensive imaging that found a pellet embolised into the right carotid artery, thrombosis of the middle cerebral artery, and development of a large right hemispheric ischaemic area. After an unsuccessful endovascular intervention, the projectile was removed during an open surgical procedure. The right hemisphere oedema required decompressive hemicraniectomy, but long term intensive care and physiotherapy resulted in a satisfactory recovery with moderate neurological sequelae. CONCLUSION: An unusual clinical presentation in combination with an absent exit wound might be symptomatic of projectile embolisation and should lead to a search for it. When the projectile position is convenient, surgical removal is the treatment of choice while an endovascular approach should be reserved for inaccessible locations or asymptomatic cases.

Quantitative analysis of drug losses administered via nasogastric tube--In vitro study.

PURPOSE: Drug administration through nasogastric tube (NGT) is a standard practice but the real amount of the delivered drug is unknown. Therefore, we designed a study to determine the losses of various dosage forms administered by different methods through NGT. METHODS: In vitro model was used. Five different administration methods (A-E) and six dosage forms (simple compressed tablets - T/S; film coated tablets - T/FC; enteric coated tablets - T/EC; capsules with powder filling - C/P; capsules containing extended release pellets - C/ER; capsules containing gastro-resistant pellets - C/GR) were investigated. Measurement was repeated six times for each drug-method combination. The overall losses were determined by gravimetry. In method A partial losses associated with each step of drug administration were also determined. RESULTS: Significant drug losses were measured (4-38%). Only methods A (crushing-beaker-syringe-water-NGT) and B (crushing-water-syringe-NGT) were suitable for administration of all tested dosage forms. Method B proved the most effective for all kinds of tablets and C/GR (p<0.05) and tended to be more effective also for C/ER (p=0.052) compared to method A. C/P showed minimal losses for both tested methods (B and E). Flushing of the drug through NGT causes major losses during drug administration compared to crushing and transfer (p<0.05). All methods for intact pellets (C-E) were found inappropriate for clinical practice due to NGT clogging. CONCLUSIONS: Choosing a suitable administration method can significantly affect the amount of drugs delivered through NGT.