Herpes Simplex Virus Hepatitis in Patients Requiring Intensive Care Unit Admission: A Retrospective, Multicenter, Observational Study.

The clinical features and short-term prognosis of patients admitted to the intensive care unit for herpes hepatitis are lacking. Of 33 patients admitted between 2006 and 2022, 22 were immunocompromised, 4 were pregnant women, and 23 died. Sixteen patients developed a hemophagocytic syndrome. Acyclovir was initiated a median (interquartile range) of 1 (0-3) day after admission.

Alternative forms of portal vein revascularization in liver transplant recipients with complex portal vein thrombosis.

BACKGROUND & AIMS: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation (LT). Extra-anatomical approaches to portal revascularization, including renoportal (RPA), left gastric vein (LGA), pericholedochal vein (PCA), and cavoportal (CPA) anastomoses, have been described in case reports and series. The RP4LT Collaborative was created to record cases of alternative portal revascularization performed for complex PVT. METHODS: An international, observational web registry was launched in 2020. Cases of complex PVT undergoing first LT performed with RPA, LGA, PCA, or CPA were recorded and updated through 12/2021. RESULTS: A total of 140 cases were available for analysis: 74 RPA, 18 LGA, 20 PCA, and 28 CPA. Transplants were primarily performed with whole livers (98%) in recipients with median (IQR) age 58 (49-63) years, model for end-stage liver disease score 17 (14-24), and cold ischemia 431 (360-505) minutes. Post-operatively, 49% of recipients developed acute kidney injury, 16% diuretic-responsive ascites, 9% refractory ascites (29% with CPA, p <0.001), and 10% variceal hemorrhage (25% with CPA, p = 0.002). After a median follow-up of 22 (4-67) months, patient and graft 1-/3-/5-year survival rates were 71/67/61% and 69/63/57%, respectively. On multivariate Cox proportional hazards analysis, the only factor significantly and independently associated with all-cause graft loss was non-physiological portal vein reconstruction in which all graft portal inflow arose from recipient systemic circulation (hazard ratio 6.639, 95% CI 2.159-20.422, p = 0.001). CONCLUSIONS: Alternative forms of portal vein anastomosis achieving physiological portal inflow (i.e., at least some recipient splanchnic blood flow reaching transplant graft) offer acceptable post-transplant results in LT candidates with complex PVT. On the contrary, non-physiological portal vein anastomoses fail to resolve portal hypertension and should not be performed. IMPACT AND IMPLICATIONS: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation. Results of this international, multicenter analysis may be used to guide clinical decisions in transplant candidates with complex PVT. Extra-anatomical portal vein anastomoses that allow for at least some recipient splanchnic blood flow to the transplant allograft offer acceptable results. On the other hand, anastomoses that deliver only systemic blood flow to the allograft fail to resolve portal hypertension and should not be performed.

SARS-CoV-2 anti-spike antibodies after a fourth dose of COVID-19 vaccine in adult solid-organ transplant recipients.

BACKGROUND: A fourth dose of SARS-CoV-2 vaccine is recommended in solid-organ transplant (SOT) recipients, but the immunogenicity is poorly known. METHODS: We conducted a retrospective, observational, monocentric study between the 1st January 2021 and 31st March 2022 of the anti-Spike antibody titers after one to four doses of vaccine in SOT. RESULTS: 825 SOT were included. Median age at first vaccine injection was 61.2 (IQR 50.9-69.3) years; 66.7 % were male; 63.4 % had received four vaccine doses. The proportion of participants with a strong humoral response (>260 BAU/mL) increased with the number of vaccine doses: 10.6 % after the 1st dose (D1), 35.1 % after the 2nd (D2), 48.5 % after the 3rd (D3), and 65.1 % after the 4th (D4) (p < 0.001). Among the tested patients, the proportion with a detectable humoral response was significantly higher after D4 than after D3 (47 % vs 22 %, p = 0.01). Liver transplant recipients had more frequently a strong humoral response after D2, D3 and D4 (OR = 5.3, 3.7 and 6.6 respectively when compared with other organ transplant recipients, p < 0.001). In kidney transplant recipients, belatacept-containing regimen was associated with a lower rate of detectable humoral (9 % vs 40 %, p = 0.025) after D3, but there was no statistical difference after D4. CONCLUSION: A fourth dose should be proposed to SOT recipients who did not developed an immune response after 3 doses. Kidney transplant recipients receiving belatacept have a poorer, although frequently detectable response.

Outcome of patients treated with molecular adsorbent recirculating system albumin dialysis: A national multicenter study.

BACKGROUND AND AIM: The molecular adsorbent recirculating system (MARS) is the most widely used device to treat liver failure. Nevertheless, data from widespread real-life use are lacking. METHODS: This was a retrospective multicenter study conducted in all French adult care centers that used MARS between 2004 and 2009. The primary objective was to evaluate patient survival according to the liver disease and listing status. Factors associated with mortality were the secondary objectives. RESULTS: A total of 383 patients underwent 393 MARS treatments. The main indications were acute liver failure (ALF, 32.6%), and severe cholestasis (total bilirubin >340 µmol/L) (37.2%), hepatic encephalopathy (23.7%), and/or acute kidney injury-hepatorenal syndrome (22.9%) most often among patients with chronic liver disease. At the time of treatment, 34.4% of the patients were listed. Overall, the hospital survival rate was 49% (95% CI: 44-54%) and ranged from 25% to 81% depending on the diagnosis of the liver disease. In listed patients versus those not listed, the 1-year survival rate was markedly better in the setting of nonbiliary cirrhosis (59% vs 15%), early graft nonfunction (80% vs 0%), and late graft dysfunction (72% vs 0%) (all P < 0.001). Among nonbiliary cirrhotic patients, hospital mortality was associated with the severity of liver disease (HE and severe cholestasis) and not being listed for transplant. In ALF, paracetamol etiology and ≥3 MARS sessions were associated with better transplant-free survival. CONCLUSION: Our study suggests that MARS should be mainly used as a bridge to liver transplantation. Survival was correlated with being listed for most etiologies and with the intensity of treatment in ALF.

Evaluation of eight biomarkers to predict short-term mortality in patients with acute severe dyspnea.

BACKGROUND: Being able to better predict risk and optimal care for patients presenting with acute dyspnea is critical. Prognostic biomarkers are well known: amino-terminal pro-B-type Natriuretic Peptide, troponin, C-reactive protein, procalcitonin. Some were more recently developed: mid-regional pro-A-type natriuretic peptide (Mid Pro-ANP), mid-regional-pro-adrenomedullin (MR-proADM), pro-endothelin, copeptin. The aim of the paper was to evaluate prognostic value of clinical findings and 8 biomarkers in patients with severe acute dyspnea. METHODS: We designed a prospective cohort study targeting patients admitted in the Emergency Department and in Intensive Care Unit of a University Hospital. Inclusion criteria were acute dyspnea with SpO2 less than 92% and/or respiratory rate (RR) greater than or equal to 25 bpm. Clinical and biological data, including biomarker levels, were recorded. The contribution of the biomarkers in the prognosis was assessed using AUC-ROC curves and by multiple logistic regression. RESULTS: Three hundred and eighty four patients (median age 74 years, 28-day mortality 17%) were enrolled. All biomarkers were available for 317 patients. Main diagnoses were sepsis in 141 cases (36.7%), and acute heart failure in 84 (21.9%) cases. All biomarkers were correlated with prognosis. Pro-ADM (AUC-ROC=0.731; 95% CI: 0.658-0.804) showed the best accuracy. The parameters independently associated with prognosis led to a clinical/biological model with an AUC=0.809 and a good calibration (P (HLchi2)=0.9). Three biomarkers added prognostic information to the model: MR-proADM (P=0.005), copeptin (P=0.006) and troponin (P=0.05). CONCLUSIONS: Biomarkers can contribute to determine the day-28 outcome of patients with acute severe dyspnea.

Complications of intravascular catheters in ICU: definitions, incidence and severity. A randomized controlled trial comparing usual transparent dressings versus new-generation dressings (the ADVANCED study).

PURPOSE: To describe all post-insertion complications involving most used intravascular access, and to determine whether the use of a new-generation transparent dressing (3M™ IV Advanced) might reduce their number and impact on ICU patient outcomes. METHODS: Patients older than 18, with an expected length of stay ≥48 h and requiring at least one central venous catheter (CVC), arterial catheter (AC), haemodialysis catheter (HDC), pulmonary arterial catheters (PAC) or peripheral venous catheter (PVC) were randomized into two groups: a new-generation transparent dressing, or the hospital's classical transparent dressing, and were followed daily for any infectious and non-infectious complications. Complications were graduated for severity by an independent international multicentre multidisciplinary panel of practitioners using a Delphi process. RESULTS: We included 628 patients, 2214 catheters (873 PVCs, 630 CVCs, 512 ACs and 199 HDCs and PACs) and 4836 dressings. Overall incidence rate was of 60.9/1000 catheter-days. The most common complication was dysfunction (34.6/1000 catheter-days), mainly for PVCs (16/1000 catheter-days) and ACs (12.9/1000 catheter-days). Infectious complications incidence rate in CVCs and ACs was of 14.5/1000, mostly due to colonization (14.2/1000 catheter-days). Thrombosis incidence was of 3.8/1000 catheter-days with severe and very severe complications in 16 cases (1.8/1000 catheter-days) and one thrombosis-related death. 3M™ IV Advanced dressing did not decrease the rate of catheters with at least a minor complication [57.37/1000 vs. 57.52/1000 catheter-days, HR 1.03, CI (0.84-1.27), p = 0.81]. Incidence rates for each single complication remained equivalent: infectious [HR 0.93 (0.62-1.40), p = 0.72], deep thrombosis [HR 0.90 (0.39-2.06), p = 0.80], extravasation and phlebitis [HR 1.40 (0.69-2.82), p = 0.35], accidental removal [1.07 (0.56-2.04), p = 0.84] and dysfunction [HR 1.04 (0.80-1.35), p = 0.79]. CONCLUSION: The ADVANCED study showed the overall risk of complications to intravascular catheters in ICU patients being dysfunction, infection and thrombosis. The 3M™ IV Advanced dressing did not decrease complication rates as compared to standard dressings.

Venous thromboembolism in the ICU: main characteristics, diagnosis and thromboprophylaxis.

Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep venous thrombosis (DVT), is a common and severe complication of critical illness. Although well documented in the general population, the prevalence of PE is less known in the ICU, where it is more difficult to diagnose and to treat. Critically ill patients are at high risk of VTE because they combine both general risk factors together with specific ICU risk factors of VTE, like sedation, immobilization, vasopressors or central venous catheter. Compression ultrasonography and computed tomography (CT) scan are the primary tools to diagnose DVT and PE, respectively, in the ICU. CT scan, as well as transesophageal echography, are good for evaluating the severity of PE. Thromboprophylaxis is needed in all ICU patients, mainly with low molecular weight heparin, such as fragmine, which can be used even in cases of non-severe renal failure. Mechanical thromboprophylaxis has to be used if anticoagulation is not possible. Nevertheless, VTE can occur despite well-conducted thromboprophylaxis.

Safety of intrahospital transport in ventilated critically ill patients: a multicenter cohort study*.

OBJECTIVES: To describe intrahospital transport complications in critically ill patients receiving invasive mechanical ventilation. DESIGN: Prospective multicenter cohort study. SETTING: Twelve French ICUs belonging to the OUTCOMEREA study group. PATIENTS: Patients older than or equal to 18 years old admitted in the ICU and requiring invasive mechanical ventilation between April 2000 and November 2010 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six thousand two hundred forty-two patients on invasive mechanical ventilation were identified in the OUTCOMEREA database. The statistical analysis included a description of demographic and clinical characteristics of the cohort, identification of risk factors for intrahospital transport and construction of an intrahospital transport propensity score, and an exposed/unexposed study to compare complication of intrahospital transport (excluding transport to the operating room) after adjustment on the propensity score, length of stay, and confounding factors on the day before intrahospital transport. Three thousand and six intrahospital transports occurred in 1,782 patients (28.6%) (1-17 intrahospital transports/patient). Transported patients had higher admission Simplified Acute Physiology Score II values (median [interquartile range], 51 [39-65] vs 46 [33-62], p < 10) and longer ICU stay lengths (12 [6-23] vs 5 [3-11] d, p < 10). Post-intrahospital transport complications were recorded in 621 patients (37.4%). We matched 1,659 intrahospital transport patients to 3,344 nonintrahospital transport patients according to the intrahospital transport propensity score and previous ICU stay length. After adjustment, intrahospital transport patients were at higher risk for various complications (odds ratio = 1.9; 95% CI, 1.7-2.2; p < 10), including pneumothorax, atelectasis, ventilator-associated pneumonia, hypoglycemia, hyperglycemia, and hypernatremia. Intrahospital transport was associated with a longer ICU length of stay but had no significant impact on mortality. CONCLUSIONS: Intrahospital transport increases the risk of complications in ventilated critically ill patients. Continuous quality improvement programs should include specific procedures to minimize intrahospital transport-related risks.

Pulmonary embolism in mechanically ventilated patients requiring computed tomography: Prevalence, risk factors, and outcome.

OBJECTIVE: To estimate the rate of pulmonary embolism among mechanically ventilated patients and its association with deep venous thrombosis. DESIGN: Prospective cohort study. SETTING: Medical intensive care unit of a university-affiliated teaching hospital. INCLUSION CRITERIA: mechanically ventilated patients requiring a thoracic contrast-enhanced computed tomography scan for any medical reason. EXCLUSION CRITERIA: a diagnosis of pulmonary embolism before intensive care unit admission, an allergy to contrast agents, and age younger than 18 yrs. INTERVENTIONS: All the mechanically ventilated patients requiring a thoracic computed tomography underwent the standard imaging protocol for pulmonary embolism detection. Therapeutic anticoagulation was given immediately after pulmonary embolism diagnosis. All the included patients underwent a compression ultrasound of the four limbs within 48 hrs after the computed tomography scan to detect deep venous thrombosis. RESULTS: Of 176 included patients, 33 (18.7%) had pulmonary embolism diagnosed by computed tomography, including 20 (61%) with no clinical suspicion of pulmonary embolism. By multiple logistic regression, independent risk factors for pulmonary embolism were male gender, high body mass index, history of cancer, past medical history of deep venous thrombosis, coma, and high platelet count. Previous prophylactic anticoagulant use was not a risk factor for pulmonary embolism. Of the 176 patients, 35 (19.9%) had deep venous thrombosis by compression ultrasonography, including 20 (57.1%) in the lower limbs and 24 (68.6%) related to central venous catheters. Of the 33 pulmonary embolisms, 11 (33.3%) were associated with deep venous thrombosis. The pulmonary embolism risk was increased by lower-limb deep venous thrombosis (odds ratio 4.0; 95% confidence interval 1.6-10) but not upper-limb deep venous thrombosis (odds ratio 0.6; 95% confidence interval 0.1-2.9). Crude comparison of patients with and without pulmonary embolism shows no difference in length of stay or mortality. CONCLUSIONS: In mechanically ventilated patients who needed a computed tomography, pulmonary embolism was more common than expected. Patients diagnosed with pulmonary embolism were all treated with therapeutic anticoagulation, and their intensive care unit or hospital mortality was not impacted by the pulmonary embolism occurrence. These results invite further research into early screening and therapeutic anticoagulation of pulmonary embolism in critically ill patients.

New materials and devices for preventing catheter-related infections.

Catheters are the leading source of bloodstream infections for patients in the intensive care unit (ICU). Comprehensive unit-based programs have proven to be effective in decreasing catheter-related bloodstream infections (CR-BSIs). ICU rates of CR-BSI higher than 2 per 1,000 catheter-days are no longer acceptable. The locally adapted list of preventive measures should include skin antisepsis with an alcoholic preparation, maximal barrier precautions, a strict catheter maintenance policy, and removal of unnecessary catheters. The development of new technologies capable of further decreasing the now low CR-BSI rate is a major challenge. Recently, new materials that decrease the risk of skin-to-vein bacterial migration, such as new antiseptic dressings, were extensively tested. Antimicrobial-coated catheters can prevent CR-BSI but have a theoretical risk of selecting resistant bacteria. An antimicrobial or antiseptic lock may prevent bacterial migration from the hub to the bloodstream. This review discusses the available knowledge about these new technologies.

New challenges in the diagnosis, management, and prevention of central venous catheter-related infections.

Catheters are the leading source of bloodstream infections in critically ill patients. Because the clinical signs of infection are nonspecific, such infections are overly suspected, which results in unnecessary removal of catheters. A conservative approach might be attempted in mild infections, whereas catheters should always be removed in cases of severe sepsis or septic shock. Nowadays, comprehensive unit-based improvement programs are effective to reduce catheter-related bloodstream infections (CR-BSIs). Rates of CR-BSI higher than 2 per 1000 catheter-days are no longer acceptable. A locally adapted checklist of preventive measures should include cutaneous antisepsis with alcoholic preparation, maximal barrier precaution, strict policy of catheter maintenance, and ablation of useless catheters. Antiseptic dressings and, to a lesser extent, antimicrobial-coated catheters, might be added to the prevention strategies if the level of infections remains high despite implementation of a prevention program. In the case of CR-BSI in intensive care units (ICUs), the catheter should be removed. In the case of persistence of fever or positive blood cultures after 3 days, inadequate antibiotic therapy, endocarditis, or thrombophlebitis should be ruled out.

FVIIa corrects the coagulopathy of fulminant hepatic failure but may be associated with thrombosis: a report of four cases.

PURPOSE: During liver transplantation, excessive blood losses are correlated with increased morbidity and mortality. Blood losses are particularly high in the case of urgent liver transplantation for fulminant hepatic failure (FHF). Recombinant activated factor VII (rFVIIa) has shown promise in treating the coagulopathy of liver disease. We review our experience with the use of rFVIIa in treating the coagulopathy of FHF during urgent liver transplantation. CLINICAL FEATURES: We report four patients with FHF who met King's College criteria for liver transplantation and in whom rFVIIa was used after conventional means for treating the associated coagulopathy had failed. In all patients, the coagulation defect was corrected by rFVIIa. However, thrombotic complications occurred in two patients (myocardial ischemia and portal vein thrombosis) and the implication of rFVIIa cannot be excluded. CONCLUSION: We conclude that rFVIIa is effective in the correction of the coagulopathy associated with FHF. However, thrombotic events are of concern and therefore, further studies are warranted to define the safety of rFVIIa in that setting.