Search Results (20)

Background: Severe acute pancreatitis (SAP) presents with Multiple Organ Dysfunction Syndrome (MODS) in ~15% of cases, accounting for ~35% of early deaths within 48 h. Major complications—shock, renal failure, and respiratory insufficiency—arise from an overwhelming systemic inflammatory response driven by markedly elevated pro-inflammatory cytokines. Massive release of IL-2, IL-6, and TNF-α underlies the systemic inflammatory response syndrome (SIRS). Continuous veno-venous hemofiltration (CVVH) with the oXiris filter, adsorbing endotoxins and cytokines, has been used in sepsis and applied early in SAP to reduce cytokine load and organ injury. Aims: To evaluate the efficacy and safety of early CVVH with the oXiris filter in modulating the systemic inflammatory response by removing toxic cytokines from the bloodstream in patients with SAP complicated by organ dysfunction and refractory sepsis. Methods: This single-centre, retrospective, observational study was conducted at a tertiary university hospital between 2000 and 2022. Forty-eight consecutive patients with SAP at onset, defined according to the 2012 Atlanta Classification, with an APACHE II score ≥ 19 and persistent organ dysfunction (>48 h), were included. All patients were unresponsive to initial intensive care within the first 24 h and underwent urgent laparotomy with extensive peritoneal lavage, pancreatic necrosectomy, and placement of multiple abdominal drains, followed by transfer to the intensive care unit. CVVH (Prismax system) with the oXiris filter was initiated within 12 h post-surgery. IL-6 and TNF-α were selected as inflammatory markers and measured in both serum and ultrafiltrate at baseline (0 h) and at 24, 48, 72, and 96 h. These measurements were correlated with clinical parameters and prognostic scores (APACHE II, SOFA). Results: Treatment was well tolerated in all patients. The 28-day survival rate was 97.9%. There was a significant time-dependent decrease in IL-6 (p = 0.019) and TNF-α (p = 0.008) concentrations in the ultrafiltrate, consistent with high early adsorption followed by a reduced cytokine burden, whereas serum levels showed a non-significant downward trend (IL-6 p = 0.08; TNF-α p = 0.310). The APACHE II score decreased from 23 postoperatively to 8 by the second week (−65.2%; p = 0.013), with a statistically significant correlation between cytokine reduction and clinical improvement. Adverse events were rare and manageable. Conclusions: Early CVVH with the oXiris filter in SAP, complicated by MODS and refractory sepsis, proved safe, well-tolerated, and potentially effective in reducing cytokine burden and improving prognostic indices. These findings support the hypothesis of a relevant immunomodulatory effect, warranting prospective controlled trials to confirm its true impact on survival and organ recovery. Full article

Background: Renal replacement therapy (RRT), widely used in the treatment of renal injury during sepsis, aims to eliminate the toxins and proinflammatory cytokines involved in the pathomechanism underlying septic shock. Dialysis filters are characterized by a high adsorption potential for cytokines in RRT in the case of septic renal injury. For the treatment of sepsis with antibiotics, it is of key importance to achieve the desired values of PK/PD indices. Continuous renal replacement therapy (CRRT) may affect antimicrobial clearance, increasing their elimination in some cases. Methods: The aim of this study was to determine the degree of adsorption for linezolid on three different types of filters used in CRRT. In our in vitro study, a continuous veno-venous hemofiltration (CVVH) was conducted using three types of filters: polysulfone (PS), polyethyleneimine-treated polyacrylonitrile (PAN PEI), and non-PEI-treated polyacrylonitrile (PAN). Each type of filter was used in three CVVH cycles, involving the use of 600 mg of linezolid dissolved in 700 mL of bovine blood or in 700 mL of 0.9% NaCl. In each case, the total volume of the obtained solution was 1000 mL. Blood samples were collected at particular time points to measure their drug concentration. The differences in mean drug/NaCl adsorption and drug/blood adsorption were determined using a one-way ANOVA with multiple comparisons via Tukey’s post hoc test; a p-value of <0.05 was considered significant. Results: A significant adsorption of linezolid was found for PAN PEI filters, both in samples obtained from bovine blood and 0.9% NaCl solutions, at the endpoint. In PAN PEI samples, the concentration of linezolid in 0.9% NaCl solutions decreased from 594.74 μg/mL to 310.66 μg/mL after 120 min (the difference was established at 52%). In blood samples, the initial concentration was 495.18 μg/mL, which then decreased to 359.84 μg/mL (73% of the beginning value). No significant adsorption was demonstrated on PAN or PS filters. Conclusion: There is a need for in vivo research to confirm the effect of filter type on linezolid concentration in patients undergoing CRRT. Full article

Continuous venovenous hemofiltation (CVVH) with citrate anticoagulation has been shown to be associated with substantial losses of calcium and negative calcium balance in ICU patients, which may lead to excessive bone loss and osteoporosis. The aim of this study is to investigate whether plasma parathormone monitoring can identify patients with negative calcium balance during CVVH. This is a retrospective single-center study of all adult ICU patients treated with citrate CVVH from 2021 to 2023. PTH was measured routinely once per week. Calcium excretion in ultrafiltrate fluid and CVVH calcium balance were measured daily. In total, 274 PTH measurements were performed in 111 patients. In 61 measurements (22%), PTH was higher than the upper limit of normal (>8 pmol/L). If PTH was higher than normal, plasma ionized calcium was less than 1.16 mmol/L in 77% of cases and hypercalcemia was never present. In a subgroup of patients treated with CVVH for at least 36 h in the preceding 72 h, PTH values were similar for quartiles by cumulative calcium balance. Increased plasma concentrations of PTH are frequently found in ICU patients treated with citrate CVVH, but no association was found between PTH and the CVVH calcium balance over the last 72 h. Full article

Introduction: Metformin, a commonly used oral antihyperglycemic drug, poses a rare risk related to the development of metformin-associated lactic acidosis (MALA). The Extracorporeal Treatments in Poisoning (EXTRIP) group recommended intermittent haemodialysis (IHD) as a primary elimination therapy in case of severe metformin poisoning. However, in haemodynamically unstable patients, our previous observations suggested that continuous venovenous haemofiltration (CVVH) might be more effective. This retrospective cohort study aimed to contribute evidence on the use of IHD and CVVH in patients with severe MALA, particularly in haemodynamically unstable patients. Methods: Data from January 2015 to December 2020 were collected from the Leuven University Hospital. Two separate search methods, based on hospital activity records and laboratory criteria, were used to identify patients with MALA. Patients diagnosed with MALA, receiving extracorporeal treatment within 24 h of admission, were included. Patients were categorized into the IHD and CVVH groups. Patient characteristics, treatment details, and outcomes were analysed. Results: Among 358,148 patient records, 35 MALA cases were identified. IHD was chosen as the initial elimination technique in 13 cases, whereas 22 patients were first commenced on CVVH. Patients treated with CVVH were sicker, had more comorbidities and had higher ventilation and vasopressor requirements. CVVH group had longer vasopressor use, longer ICU stays, and higher in-hospital mortality. Discussion: CVVH rather than IHD seems to be the preferred elimination technique in the more critically ill patients with MALA. Due to its retrospective design, this study failed to identify the superior elimination technique in terms of efficacy. Poorer outcomes in the CVVH group are likely attributed to the severity of illness rather than the inferiority of the elimination therapy. We acknowledge the diagnostic challenges regarding MALA. Using metformin assays could be beneficial in managing these patients. Conclusions: This study suggests clinicians’ preference for CVVH in severe cases of MALA with haemodynamic instability. Full article

Candidemia is a serious health threat. Whether this infection has a greater incidence and a higher mortality rate in patients with COVID-19 is still debated. In this multicenter, retrospective, observational study, we aimed to identify the clinical characteristics associated with the 30-day mortality in critically ill patients with candidemia and to define the differences in candidemic patients with and without COVID-19. Over a three-year period (2019–2021), we identified 53 critically ill patients with candidemia, 18 of whom (34%) had COVID-19 and were hospitalized in four ICUs. The most frequent comorbidities were cardiovascular (42%), neurological (17%), chronic pulmonary diseases, chronic kidney failure, and solid tumors (13% each). A significantly higher proportion of COVID-19 patients had pneumonia, ARDS, septic shock, and were undergoing an ECMO procedure. On the contrary, non-COVID-19 patients had undergone previous surgeries and had used TPN more frequently. The mortality rate in the overall population was 43%: 39% and 46% in the COVID-19 and non-COVID-19 patients, respectively. The independent risk factors associated with a higher mortality were CVVH (HR 29.08 [CI 95% 3.37–250]) and a Charlson’s score of > 3 (HR 9.346 [CI 95% 1.054–82.861]). In conclusion, we demonstrated that candidemia still has a high mortality rate in patients admitted to ICUs, irrespective of infection due to SARS-CoV-2. Full article

Background: Cefiderocol is a novel parenteral siderophore cephalosporin, demonstrating enhanced activity against multidrug-resistant (MDR) Gram-negative bacteria and difficult-to-treat Acinetobacter baumannii (DTR-AB). Plasma-free trough concentration (fC_trough) over the minimum inhibitory concentration (MIC) was reported as the best pharmacokinetic parameter to describe the microbiological efficacy of cefiderocol. Materials and methods: We retrospectively described the pharmacokinetic and pharmacodynamic profile of three critically ill patients admitted to the intensive care unit, receiving cefiderocol under compassionate use to treat severe DTR-AB infections while undergoing continuous venovenous haemofiltration. Cefiderocol was administrated at a dosage of 2 g every 8 h infused over 3 h. Therapeutic drug monitoring (TDM) was assessed at the steady state. Cthrough was evaluated by assuming a plasma protein binding of 58.0%. The fCmin/MIC was calculated assuming a cefiderocol MIC equal to the PK-PD breakpoint of susceptibility ≤ 2. The association between the PK/PD parameters and microbiological outcome was assessed. Results: fC_trough/MIC were >12 in 2 patients and 2.9 in the 1 who rapidly recovered from renal failure. Microbiological cure occurred in 3/3 of patients. None of the 3 patients died within 30 days. Conclusions: A cefiderocol dosage of 2 g q8 h in critically ill patients with AKI undergoing CVVH may bring about a very high plasma concentration, corresponding to essentially 100% free time over the MIC for DTR-AB. Full article

The proper posology of antibiotics in the critically ill in CRRT is difficult to assess. We therefore performed a prospective observational cohort study to make clear hints in this topic. Our results reveal a high Sieving Coefficient for all antibiotics, equal to or higher than those described in previous papers. CVVH clearance in relation to total body clearance was significant, (i.e., >than 25% for all classes). A strong correlation between the antibiotic concentrations obtained in plasma and ultrafiltrate was found both at the peak and in the valley, with the determination of two equations that allow a new method for calculating the amount of antibiotic lost in CVVH both for trough levels and peak. Based on the results of our study and considering the limitations we believe that we can extrapolate the following final considerations: (1) it is likely to carry out a loading dose for the main antibiotics (2) subsequent administrations must take into account the daily loss identified by the linear regression equation. This angular coefficient gives the idea that the average daily loss of given antibiotic is about 25%; this implies that on the basis of the linear regression equation that correlates ultrafiltered/plasma antibiotic concentration, the dosage should be increased by 25% every day, while still ensuring a daily plasma TDM of the drug. Full article

Background: The present study evaluates outcomes of LVAD patients, taking into account the device strategy and the INTERMACS profile. Methods: We included 192 LVAD-patients implanted between January 2012 and May 2021. The primary and secondary end-points were survival and major adverse events between Profiles 1–3 vs. Profile 4, depending on implantation strategies (Bridge-to-transplant-BTT; Bridge-to-candidacy-BTC; Destination-Therapy-DT). Results: The overall survival was 67% (61–75) at 12 months and 61% (54–70) at 24 months. Profile 4 patients showed significantly higher survival (p = 0.018). Incidences of acute right-ventricular-failure (RVF) (p = 0.046), right-ventricular-assist-device (RVAD) implantation (p = 0.015), and continuous-venovenous-hemofiltration (CVVH) (p = 0.006) were higher in Profile 1–3 patients, as well as a longer intensive care unit stays (p = 0.050) and in-hospital-mortality (p = 0.012). Twelve-month and 24-month survival rates were higher in the BTT rather than in BTC (log-rank = 0.410; log-rank = 0.120) and in DT groups (log-rank = 0.046). In the BTT group, Profile 1–3 patients had a higher need for RVAD support (p = 0.042). Conclusions: LVAD implantation in elective patients was associated with better survival and lower complications incidence. LVAD implantation in BTC patients has to be considered before their conditions deteriorate. DT should be addressed to elective patients in order to guarantee acceptable results. Full article

An 80-year-old man was admitted with an L5 compression fracture, L4/5 spondylolisthesis, and L5 radiculopathy and underwent a TLIF procedure. Refractory hypotension occurred, though it indicated a possible great vessel injury with vasopressor and fluid infusion. Emergent intraoperative angiography was performed, which showed extravasation at the right common iliac artery. Resuscitative endovascular balloon occlusion of the aorta followed by right common iliac artery stenting was successfully performed to arrest the bleeding. The iatrogenic right common iliac artery laceration was complicated with abdomen compartment syndrome and acute kidney injury. The patient received supportive care, including continuous venovenous hemofiltration (CVVH) for a week, after which the patient’s condition improved. The patient did not have any residual complications at the one-month follow-up. Great vessel injury during the TLIF procedure is rare but fatal. Refractory hypotension is indicative of a great vessel injury. Endovascular intervention is a fast and promising method to diagnose and treat arterial injury. Full article

Background: Some research indicated that hypothyroidism has huge adverse effects for the metabolic, cardiovascular, respiratory, and immune systems. However, there is no confirmed conclusion for the effect of cardiovascular surgery. This cohort study aims to investigate the prognosis of hypothyroidism patient at the age under 65-year-old after coronary artery bypass grafting (CABG) surgery. Method: From the National Health Insurance Research Database of Taiwan, 1586 patients with hypothyroidism who underwent elective CABG surgery were selected, along with 6334 patients who underwent surgery in a ratio of 1:4 sex-, age- and index year-matched controls, who were out of hypothyroidism. We used Cox proportional hazard analysis to compare the rate of 30-day, 5-year mortality, post-operative atrial fibrillation, respiratory complication during an average of 10-year follow-up. Result: Post-CABG patients had more hospital days, which was associated with hypothyroidism, male, DM and higher CCI_R (p < 0.001). Post-CABG patients had more inpatient respiratory complications, which was associated with hypothyroidism (p = 0.041), DM and CCI_R (p < 0.001, p = 0.046), and there was no difference in 1-year respiratory complication, tracheostomy in the same hospital course and within 1 year, repeated PCI, Af, CVVH, cerebral infarction, 30-day and 5-year mortality rate. Conclusions: Hypothyroidism correlates to post-CABG ventilator-related complications and pneumonia, and prolonged hospital days, but no effect on 30-day, 5-year mortality, post-operative atrial fibrillation and cerebral infarction rate. Thyroid function survey might include routinely preoperative survey for CABG outcome prognosis. Full article

Acute kidney injury (AKI) is a frequent complication in critically ill patients. Supportive treatment of AKI patients is based on renal-replacement therapy, including continuous veno-venous hemofiltration (CVVH). To limit clotting events on extracorporeal surfaces, anticoagulants are administered, including systemic heparin and local citrate. The differential and comparative effects of these anticoagulants on leukocyte function in acute kidney injury patients are, so far, insufficiently understood. In this bio-add-on-study, AKI patients were randomized as part of a parallel-group trial to either systemic heparin or regional citrate anticoagulation. Patient samples were collected upon inclusion, prior to CVVH initiation at day 0, day 1, day 3 and day 5, following CVVH initiation, and one day after cessation of CVVH, then immediately analyzed. Flow cytometric assessment of surface-receptor molecules was conducted. Whole-blood-perfused human microfluidic chambers were used for the analysis of neutrophil rolling and adhesion. Acute kidney injury was associated with significant changes in the surface expression of CD182 and CD16 throughout CVVH treatment, independent of the anticoagulation regime. AKI furthermore abrogated selectin-induced slow leukocyte rolling and diminished chemokine-induced leukocyte arrest. Subgroup analyses of citrate vs. heparin treatment showed no significant differences between groups, independent of the duration of CVVH treatment. CD182 and CD16 expression remained low in both groups throughout CVVH therapy. These data confirm that AKI impairs selectin-mediated leukocyte slow rolling and chemokine-induced leukocyte arrest in vitro. Systemic heparin or local citrate anticoagulation have no differential effect on the leukocyte recruitment steps examined in this study. Full article

(1) Background: Nutrition therapy guided by indirect calorimetry (IC) is the gold standard and is associated with lower morbidity and mortality in critically ill patients. When performing IC during continuous venovenous hemofiltration (CVVH), the measured VCO₂ should be corrected for the exchanged CO₂ to calculate the ‘true’ Resting Energy Expenditure (REE). After the determination of the true REE, the caloric prescription should be adapted to the removal and addition of non-intentional calories due to citrate, glucose, and lactate in dialysis fluids to avoid over- and underfeeding. We aimed to evaluate this bioenergetic balance during CVVH and how nutrition therapy should be adapted. (2) Methods: This post hoc analysis evaluated citrate, glucose, and lactate exchange. Bioenergetic balances were calculated based on these values during three different CVVH settings: low dose with citrate, high dose with citrate, and low dose without citrate. The caloric load of these non-intentional calories during a CVVH-run was compared to the true REE. (3) Results: We included 19 CVVH-runs. The bioenergetic balance during the low dose with citrate was 498 ± 110 kcal/day (range 339 to 681 kcal/day) or 26 ± 9% (range 14 to 42%) of the true REE. During the high dose with citrate, it was 262 ± 222 kcal/day (range 56 to 262 kcal/day) or 17 ± 11% (range 7 to 32%) of the true REE. During the low dose without citrate, the bioenergetic balance was −189 ± 77 kcal/day (range −298 to −92 kcal/day) or −13 ± 8% (range −28 to −5%) of the true REE. (4) Conclusions: Different CVVH settings resulted in different bioenergetic balances ranging from −28% up to +42% of the true REE depending on the CVVH fluids chosen. When formulating a caloric prescription during CVVH, an individual approach considering the impact of these non-intentional calories is warranted. Full article

The history of continuous renal replacement therapy (CRRT) is marked by technological advances linked to improvements in the knowledge of the mechanisms and kinetics of extracorporeal removal of solutes, and the pathophysiology of acute kidney injury (AKI) and other critical illnesses. In the present article, we review the main steps in the history of CRRT, from the discovery of continuous arteriovenous hemofiltration to its evolution into the current treatments and its early use in the treatment of AKI, to the novel sequential extracorporeal therapy. Beyond the technological advances, we describe the development of new medical specialties and a shared nomenclature to support clinicians and researchers in the broad and still evolving field of CRRT. Full article

The optimal dose of vancomycin in critically ill patients receiving continuous venovenous hemofiltration (CVVH) remains unclear. The objective of this study was to identify factors that significantly affect pharmacokinetic profiles and to further investigate the optimal dosage regimens for critically ill patients undergoing CVVH based on population pharmacokinetics and pharmacodynamic analysis. A prospective population pharmacokinetic analysis was performed at the surgical intensive care unit in a level A tertiary hospital. We included 11 critically ill patients undergoing CVVH and receiving intravenous vancomycin. Serial blood samples were collected from each patient, with a total of 131 vancomycin concentrations analyzed. Nonlinear mixed effects models were developed using NONMEM software. Monte Carlo Simulation was used to optimize vancomycin dosage regimens. A two-compartment model with first-order elimination was sufficient to characterize vancomycin pharmacokinetics for CVVH patients. The population typical vancomycin clearance (CL) was 1.15 L/h and the central volume of distribution was 16.9 L. CL was significantly correlated with ultrafiltration rate (UFR) and albumin level. For patients with normal albumin and UFR between 20 and 35 mL/kg/h, the recommended dosage regimen was 10 mg/kg qd. When UFR was between 35 and 40 mL/kg/h, the recommended dosage regimen was 5 mg/kg q8h. For patients with hypoalbuminemia and UFR between 20 and 25 mL/kg/h, the recommended dosage regimen was 5 mg/kg q8h. When UFR was between 25 and 40 mL/kg/h, the recommended dosage regimen was 10 mg/kg q12h. We recommend clinicians choosing the optimal initial vancomycin dosage regimens for critically ill patients undergoing CVVH based on these two covariates. Full article

Cardiovascular catheterization has been applied in infant treatment for several decades. To date, considerable research attention has been paid to cardiovascular catheterization in small neonates. However, peripheral vascular routes of catheterization are possible obstacles for interventionists. Umbilical vein catheterization has been reported as a route for neonates, although few attempts have been made to investigate this approach. This study aimed to retrospectively review cardiovascular intervention using the umbilical vein approach as applied to infants admitted to a tertiary center from 2017 to 2020. Details including the perinatal variables, indication diagnoses, and procedure devices were collected. The enrollment included a total of 16 cases representing 17 intervention events, with infants born at a gestation age of 22–39 weeks and body weight ranging from 478 to 3685 g at the time of the procedure. The postnatal age ranged from 1 to 27 days. The catheter sizes ranged from 4 to 11 Fr. Indications included being admitted for patent ductus arteriosus occlusion (n = 15), balloon pulmonary valvuloplasty (n = 3), balloon atrial septostomy (BAS) (n = 3), pulmonary valve (PV) perforation (n = 1), and two interventions for catheter placement for continuous venovenous hemofiltration. The success rate for cardiovascular catheterization was 88.2% (15/17). There were two patients for which cannulation failed due to ductus venosus closure: one intraabdominal hemorrhage complication during continuous venovenous hemofiltration (CVVH), and one cardiac catheterization failure of PV perforation due to failure to insert the guiding catheter into the right ventricular outflow tract. Based on these findings, we conclude that cardiac catheterization and the placement of a large-sized catheter through an umbilical vein in a small infant represents a safe and time-saving method when catheterization is required. Full article