Xia Zheng

Introduction: Carbapenem-resistant organisms (CROs) threaten critically ill patients, requiring model-informed ceftazidime-avibactam (CAZ-AVI) dosing by renal function and renal replacement therapy (RRT) status. Materials and Methods: Thirty-three patients were prospectively enrolled at one center (18 RRT; 15 non-RRT). RRT settings were recorded. Samples were collected at 0, 1, 2, 4, 6, and 8 h after first-dose and steady-state infusions. Population pharmacokinetic modeling used NONMEM. Monte Carlo simulations evaluated joint probability of target attainment (PTA) for minimum inhibitory concentration (MIC)-directed therapy and pathogen-specific cumulative fraction of response (CFR) for empirical therapy using BRICS MIC distributions under two targets: (1) CAZ 100% fT > MIC and AVI 100% fT > 1 mg/L; and (2) CAZ 50% fT > 4MIC and AVI 50% fT > 1 mg/L. Robust model-informed regimens required joint PTA ≥ 90% under both targets for MIC-directed therapy and CFR ≥ 90% under both for empirical therapy; lower values were exploratory. Results: We analyzed 211 blood samples (120 RRT; 91 non-RRT). Creatinine clearance (CrCL) was retained in the final non-RRT models, whereas no covariate was retained in the final RRT models. RRT-model clearance (CL)/volume of distribution (V_d) estimates were 2.03 L/h/17.0 L for CAZ and 1.77 L/h/14.0 L for AVI; non-RRT estimates were 3.36 L/h/20.5 L and 4.27 L/h/16.0 L, respectively. At MICs ≤ 8 mg/L, robust model-informed regimens included 2000/500 mg q6h for augmented renal clearance and 2000/500 mg q12h during RRT. For CFR-based empirical therapy during RRT, robust model-informed regimens were 2000/500 mg q12h for carbapenem-resistant Klebsiella pneumoniae (CRKP) and 2000/500 mg q8h for carbapenem-resistant Pseudomonas aeruginosa (CRPA). Conclusion: Our study describes the pharmacokinetics of CAZ-AVI in critically ill patients and provides model-informed dosing regimens stratified by renal function and RRT status for both empirical and targeted therapy. Larger, multicenter prospective studies are warranted to validate these findings.

Background: Left ventricular assist device (LVAD) implantation is a common intervention for patients with end-stage heart failure. However, comorbid chronic obstructive pulmonary disease (COPD) poses significant challenges in perioperative management. In such cases, ultrafast track anesthesia (UFTA) has been proposed to minimize cardiopulmonary disturbances and promote rapid recovery. Case: This report describes the case of a 53-year-old man diagnosed with dilated cardiomyopathy and COPD. Despite extensive medical treatment, the patient's condition did not improve, and his activities were strictly limited (New York Heart Association Class IV). Echocardiography revealed an enlarged heart with an ejection fraction of 24%. The patient was scheduled to undergo LVAD implantation via minimally invasive surgery. An UFTA protocol based on propofol and remifentanil was consequently designed and implemented. Postoperatively, the patient regained consciousness and exhibited stable respiratory function and hemodynamic parameters. On-table extubation was performed, and the patient was transferred to the intensive care unit. However, he received a butorphanol infusion after surgery and had to be re-intubated 23 h later. Conclusions: This case reveals that if a multidisciplinary team effort and tailored treatment protocols had not been executed, reintubation may not have been avoided, even though the patient had been extubated in the operating room shortly after surgery.

Methylprednisolone is still used to treat adults with septic shock in real-world clinical settings, despite current international guidelines recommending hydrocortisone. The aim of this study was to assess the effect of methylprednisolone vs hydrocortisone on 30-day mortality among critically ill patients with septic shock. We conducted a retrospective cohort study on adults with septic shock using the MIMIC-IV v3.0 database. Patients who received methylprednisolone after diagnosis were matched using propensity score matching (PSM) with those received hydrocortisone, to balance confounding factors between groups. The primary outcome was the 30-day mortality rate. Subgroup and sensitivity analyses were performed to assess the robustness of the conclusions. A total of 1,607 septic shock patents were enrolled in this study, with an overall 30-day mortality rate of 42.1%. After 1:1 PSM, 376 pairs were successfully matched. The primary outcome occurred in 141 patients (37.5%) and in 131 patients (34.8%) in the methylprednisolone and hydrocortisone groups, respectively (HR = 1.105, 95% CI: 0.871–1.402, P = 0.410). In subgroup analyses based on age, sex, blood culture positivity, pneumonia, and invasive mechanical ventilation (IMV), along with sensitivity analyses for deletion of missing values, findings remained consistent. However, the methylprednisolone group exhibited a longer ICU stay, elevated blood glucose levels, and a shorter maintenance duration for vasopressin compared to the hydrocortisone group. Among adults with septic shock, there was no significant difference in 30-day mortality between those administered methylprednisolone and hydrocortisone. It needs to be further verified in prospective, randomized controlled trials.

Background: Respiratory mechanics and gas exchange parameters are readily accessible indicators for evaluating ventilation in patients with acute respiratory distress syndrome (ARDS). Computed tomography (CT) is a widely used radiological imaging technique, while electrical impedance tomography (EIT) is a novel technique for pulmonary function monitoring developed in recent years. Studies suggest that EIT combined with quantitative CT holds unique value in assessing ventilation/perfusion (V/Q) function. Unlike classic ARDS, the pathophysiologic alterations in ARDS following lung transplantation are complex, and the specific mechanisms remain unclear. This study aims to explore the use of respiratory mechanics, gas exchange parameters, EIT, and quantitative CT for the multimodal assessment of V/Q function in post‐lung transplantation ARDS. We further aim to integrate visualizing dynamic imaging and regional quantitative lung analysis into this multimodal assessment system. Method: We retrospectively enrolled lung transplant recipients admitted to the intensive care unit who met the Berlin criteria for ARDS. Inclusion required an arterial partial pressure of oxygen to fraction of inspired oxygen ratio (P/F) ≤ 300 mmHg, with both EIT monitoring of V/Q and high‐resolution CT performed within 24 h of documented P/F ≤ 300 mmHg. Patient baseline characteristics, respiratory mechanics parameters, gas exchange parameters, EIT data, and CT images were collected. Subjects were stratified into two groups according to P/F values: a low P/F group (P/F < 200 mmHg) and a high P/F group (200 mmHg ≤ P/F ≤ 300 mmHg). Ventilation parameters derived from EIT included global inhomogeneity index (GI), center of ventilation (COV), and regional ventilation delay index (RVDI). Using hypertonic saline contrast‐enhanced EIT, we acquired V/Q parameters and calculated both global and regional EIT‐based dead space fraction (EIT‐Dead Space), intrapulmonary shunt fraction (EIT‐Shunt), and V/Q matching (EIT‐V/Q Match). Chest CT images were processed through a multitask learning U‐net‐based computer‐aided diagnostic model. This enabled semiautomated lung segmentation, identification of high‐density lesions, quantitative analysis, and three‐dimensional visualization. Pulmonary volumes, lesion volumes, and percentage lesion volumes (calculated as lung lesion volume divided by lung volume) were, respectively, quantified for the left and right lungs. Result: The study ultimately enrolled 21 lung transplant recipients with ARDS, comprising five patients in the low P/F group and 16 in the high P/F group. Among 21 patients, the low P/F group demonstrated significantly higher ventilation ratio (VR), RVDI, and EIT‐Dead Space, along with lower EIT‐V/Q match levels compared to the high P/F group, while no significant difference in EIT‐Shunt was observed between the two groups. EIT‐Dead Space showed substantial agreement with ventilator‐measured dead space fraction, and VR exhibited a significant positive correlation with EIT‐Dead Space. In the two groups, quantitative CT‐derived pulmonary metrics—including lung volume, lesion volume, and percentage lesion volume—showed no significant differences between the low and high P/F groups. Conclusion: Among lung transplant recipients with ARDS, the low P/F group demonstrated elevated VR, RVDI, and EIT‐Dead Space, alongside reduced EIT‐V/Q matching levels when compared to the high P/F group. Notably, no significant differences were found in the quantitative CT‐derived lesion volume parameters between the two groups.

Nasogastric tubes (NGTs) are commonly used in the intensive care unit (ICU) and are often inserted blindly at the bedside. Previous studies have highlighted various complications associated with NGT misplacement, including epistaxis, pneumothorax and even fatal perforations. To reduce the incidence of complications, guidelines recommend confirming the correct position of the NGT through radiography, pH testing, end‐expiratory carbon dioxide monitoring, ultrasonography, etc. Herein, we present the case of a 78‐year‐old man who experienced sudden dyspnoea, was brought to the ICU and subsequently developed gastrointestinal bleeding following improper NGT placement. In this patient, air was rapidly injected down the NGT while auscultating for a ‘whooshing sound’ over the epigastrium. However, the correct position of the NGT was eventually confirmed by X‐ray. Urgent upper gastrointestinal endoscopy revealed an oesophagogastric submucosal tunnelling of the NGT. This case emphasizes that auscultation may be unreliable and no longer encouraged. Additionally, various verification methods may not detect such rare complications related to NGT placement, making it necessary to focus on the emerging clinical manifestations following NGT insertion. Moreover, gaining further insight into the history of gastrointestinal diseases in patients may be beneficial. Relevance to Clinical Practice: This case underscores the importance of noting resistance during a blind nasogastric tube (NGT) insertion in the intensive care unit (ICU). Additionally, the ‘whooshing testing’ for tube placement verification is not recommended. Although radiographic confirmation remains the gold standard, it may not effectively identify rare complications. Furthermore, emerging clinical signs (such as the abnormal nature of the gastrointestinal decompression drainage fluid, hypotension and anaemia) after insertion may suggest NGT misalignment. Finally, in urgent ICU settings, the patient's history of gastrointestinal disease should not be overlooked, as it can lead to complications such as gastrointestinal bleeding.

Evidence-based data regarding the timing of the application of invasive mechanical ventilation among adults with septic shock is insufficient. The guidelines fail to provide clear advice about the optimal time to initiate this support. Consequently, we aimed to investigate whether early intubation could improve survival rates in septic shock patients. We conducted a retrospective analysis of the MIMIC-IV database to evaluate the effectiveness of early intubation on mortality in a cohort of septic shock patients. Adults diagnosed with septic shock, according to the Sepsis-3 definition, were included. They were categorized into an early intubation group (first 8 h after vasopressor initiation) and a non-early intubation group (unexposed). A propensity score matching (PSM) analysis was used to balance the baseline characteristics between the two groups. The primary outcomes were 30-day and 90-day all-cause mortality rates. In addition, we employed the restricted cubic spline to analyze the potential non-linear relationship between the timing of intubation and 30-day or 90-day all-cause mortality. A total of 6864 adult patients, of whom 2048 were intubated in the first 8 h, were evaluated in the final cohort. Following a 1:1 PSM procedure, 2786 patients were successfully paired. At 30 days, 288 of 1393 patients (20.7%) in the early intubation group and 381 of 1393 patients (27.4%) in the non-early intubation group had died (hazard ratio [HR] 0.717; 95% confidence interval [CI] 0.616–0.836; p < 0.001). Similarly, the results also showed that early intubation was associated with a lower 90 day all-cause mortality rate (HR 0.761; 95% CI 0.663–0.874; p < 0.001). Furthermore, ICU and hospital lengths of stay were significantly different between the groups (3.6 [1.9, 7.1] vs. 2.3 [1.3, 4.3]; p < 0.001 and 8.9 [5.4, 15.1] vs. 7.2 [4.5, 12.0]; p < 0.001). In the subgroup analysis, we further confirmed the robustness of our findings. Additionally, we found that the timing of intubation is inversely U-shaped correlated to the 30 day all-cause mortality rate. Among adult patients with septic shock, the early initiation of invasive mechanical ventilation could improve clinical outcomes. The timing of intubation demonstrated an inverse U-shaped association with the 30 day all-cause mortality rate, with the peak risk of death occurring at 50.5 h after septic shock.

Background: Posttransplant lymphoproliferative disorders (PTLDs) are uncommon but serious complications in patients following solid organ transplantation. Primary Epstein-Barr virus (EBV) infection is a risk factor for the development of PTLD, especially early-onset PTLD, in EBV-negative recipients. To date, however, there are no specific guidelines on the threshold of EBV-DNA load for therapeutic intervention, the source for measurement (e.g., blood, bronchoalveolar fluid), or the use of antiviral agents as prophylaxis for early PTLD prevention in EBV-mismatched patients.Methods: The present study describes a 56-year-old male lung transplant recipient diagnosed with EBV-associated PTLD.Results: This patient had a history of invasive fungal disease and Mucor and Aspergillus fumigatus infections in the early post-transplant period, necessitating antifungal therapy throughout the course of the disease. The patient was EBV-positive 15 days after transplantation, with lung CT showing multiple bilateral nodules of varying sizes beginning 98 days after transplantation. A lung biopsy showed PTLD, and next-generation sequencing (NGS) revealed EBV. This patient, however, did not receive any antiviral therapy for early PTLD prevention or any PTLD-related treatment. He died 204 days after lung transplantation.Conclusion: The present study describes a lung transplant recipient who developed EBV-associated PTLD, a non-negligible disease, after solid organ transplantation. Monitoring EBV-DNA load is important, as a sudden increase may be a sensitive indicator of PTLD. An earlier diagnosis may increase the likelihood of successful treatment.