Effects of the timing of administration of IgM- and IgA-enriched intravenous polyclonal immunoglobulins on the outcome of septic shock patients

Background: The administration of endovenous immunoglobulins in patients with septic shock could be beneficial and preparations enriched with IgA and IgM (ivIgGAM) seem to be more effective than those containing only IgG. In a previous study Berlot et al. demonstrated that early administration of ivIgGAM was associated with lower mortality rate. We studied a larger population of similar patients aiming either to confirm or not this finding considering also the subgroup of patients with septic shock by multidrug-resistant (MDR) pathogens. Methods: Adult patients with septic shock in intensive care unit (ICU) treated with ivIgGAM from August 1999 to December 2016 were retrospectively examined. Collected data included the demographic characteristics of the patients, the diagnosis at admission, SOFA, SAPS II and Murray Lung Injury Score (LIS), characteristics of the primary infection, the adequacy of antimicrobial therapy, the delay of administration of ivIgGAM from the ICU admission and the outcome at the ICU discharge. Parametric and nonparametric tests and logistic regression were used for statistic analysis. Results: During the study period 107 (30%) of the 355 patients died in ICU. Survivors received the ivIgGAM earlier than nonsurvivors (median delay 12 vs 14 h), had significantly lower SAPS II, SOFA and LIS at admission and a lower rate of MDR- and fungal-related septic shock. The appropriateness of the administration of antibiotics was similar in survivors and nonsurvivors (84 vs 79%, respectively, p: n.s). The delay in the administration of ivIgGAM from the admission was associated with in-ICU mortality (odds ratio per 1-h increase = 1.0055, 95% CI 1.003\u20131.009, p < 0.001), independently of SAPS II, LIS, cultures positive for MDR pathogens or fungi and onset of septic shock. Only 46 patients (14%) had septic shock due to MDR pathogens; 21 of them (46%) died in ICU. Survivors had significantly lower SAPS II, SOFA at admission and delay in administration of ivIgGAM than nonsurvivors (median delay 18 vs 66 h). Even in this subgroup the delay in the administration of ivIgGAM from the admission was associated with an increased risk of in-ICU mortality (odds ratio 1.007, 95% CI 1.0006\u20131.014, p = 0.048), independently of SAPS II. Conclusions: Earlier administration of ivIgGAM was associated with decreased risk of in-ICU mortality both in patients with septic shock caused by any pathogens and in patients with MDR-related septic shock

Management of tricyclic antidepressant poisoning

Although a number of more recent substances with fewer side effects have become available for the treatment of depression, tricyclic antidepressants (TCA) are still commonly used. In addition, they are used for the treatment of neuropathic pain. The common basic mechanism of action is inhibition of reuptake of different neuromediators at the presynaptic terminal in both the central nervous system (CNS) and peripheral tissues, with the subsequent prolongation of their effect on the post-synaptic membrane. The earliest drug of this class was imipramine. Despite a phenothiazine-like structure it was not effective for the treatment of schizophrenia; quite unexpectedly, it improved depressive symptoms. Consequently, these substances and the derived TCAs became the first line of treatment for depression until the development of the selective serotonin reuptake inhibitors (SSRI). Although all TCAs share the same mechanisms of action, there are some differences in terms of the mediator involved. Whereas imipramine and some of its derivates, including amitriptyline and doxepin, block the reuptake of noradrenaline and serotonin at the presynaptic terminals, clomipramine has a more selective action on serotonin. After oral administration, TCAs are promptly absorbed and achieve peak blood concentrations in 2\u20136 hours; their absorption is reduced by antacids and drugs with anticholinergic effects. Being highly lipophilic, TCAs are rapidly taken up by the CNS. They are metabolized in the liver through oxidation and glucoronization. Although they undergo a relevant enterohepatic circulation, they are primarily eliminated through the kidney, with a half-life of 12\u201324 hours depending on the specific drug

The Effects of Hemoadsorption on the Kinetics of Antibacterial and Antifungal Agents

The extracorporeal elimination of a pathogen or damage-associated molecular pattern via blood purification techniques is increasingly being used in patients with septic shock and other clinical conditions characterized by a life-threatening inflammatory response. The removal of these substances can be accomoplished by means of ultrafiltration or hemoadsorption. Independently from the blood putification technique used, they could also affect the clearance of antibacterial and antifungal agents with a potentially significant clinical impact. In our review, we describe the basic principles of ultrafiltration and hemoadsorption, the available devices for this latter and the existing experimental and clinical studies; the final paragraph is dedicated to practical considerations that can help clinicians to consider the clearance of antibiotics and antifungals attributable to these techniques to minimize the risk of a iatrogenic underdosage

Widespread Arterial Thrombosis after ChAdOx1 nCov-19 Vaccination

6A worldwide anti-SARS-CoV-2 immunization campaign commenced at the end of 2020 using different vaccines that induce the production of an immunological response against the viral spike protein (Sp). To this aim, two different strategies are used: the first takes advantage of S-encoding mRNA carried inside the cells by lipid nanoparticles (BNT162B2, Pfizer-BioNTech; mRNA-1273, Moderna), while the other uses engineered adenoviruses (ChAdOx1 nCov-19, AstraZeneca; Ad.26.COV2.S, Johnson & Johnson), whose genes coding for replication have been disabled and replaced with others encoding the Sp. Although all these preparations can cause transient flu-like symptoms, adenovirus-based vaccines have been associated with extremely rare occurrence (<1 case/100,000 doses) of a syndrome resembling heparininduced thrombocytopenia (HIT), appearing 7–14 days after the injection and whose main features are the reduction of the platelet count and the formation of venous thrombi in both common and uncommon sites, including the cerebral venous sinuses (CVS) and portal system [1, 2]. A cause–effect relationship with the vaccine has been hypothesized by some authors, who described this condition as vaccine-induced thrombotic thrombocytopenia (VITT) [3].openopenBerlot, Giorgio; Tomasini, Ariella; La Fata, Cristina; Pintacuda, Stefania; Rigutti, Sara; Falanga, AnnaBerlot, Giorgio; Tomasini, Ariella; La Fata, Cristina; Pintacuda, Stefania; Rigutti, Sara; Falanga, Ann

Fatal Septic Shock in a Patient with Hemophagocytic Lymphohistiocytosis Associated with an Infectious Mononucleosis

6noThe authors describe the case of a young woman who developed a clinical pictures resembling a septic shock-related multiple organ dysfunction syndrome a couple of months after having been diagnosed suffering from a hemophagocytic lymphohistiocytosis associated with an infectious mononucleosis. Despite the aggressive treatment, which included antibiotics, vasopressors, IV immunoglobulins, and the use of an extracorporeal device aimed to remove mediators released both during sepsis and the cytokine storm determined by the hemophagocytic lymphohistiocytosis, the patient died. At the autopsy, an extremely uncommon aggressive lymphoma of Epstein-Barr virus-positive T-lymphocytes with systemic involvement was discovered.openopenBerlot, Giorgio; Tomasini, Ariella; Zandonà, Lorenzo; Leonardo, Eugenio; Bussani, Rossana; Zarrillo, NadiaBerlot, Giorgio; Tomasini, Ariella; Zandonà, Lorenzo; Leonardo, Eugenio; Bussani, Rossana; Zarrillo, Nadi

Effects of the Selective Decontamination of the Digestive Tract (SDD) on Pulmonary Secondary Infections in Patients with COVID-19 Acute Respiratory Distress Syndrome: A Retrospective Single Centre Experience

Definitive data on the incidence rate of ventilator-associated pneumonia (VAP) in COVID-19 are still lacking, ranging from 29 to 58%. To date, most of the existing literature refers to patients who are not subjected to VAP prevention with selective decontamination of the digestive tract (SDD). We retrospectively collected data on all COVID-19 patients admitted to our ICU during the second phase of the pandemic with the aim of assessing the occurrence of VAP and the related mortality at 30 days and comparing our findings with the available literature. Of 213 patients, only 74 were eligible for the analysis. An incidence of 6.90 VAP per 1000 days of mechanical ventilation was detected. Apart from a smoking habit (0% vs. 10%, p p = 0.026), patients who developed VAP did not differ significantly from those who did not regarding comorbidities, steroid use, and the severity of COVID-19. VAP were predominantly caused by mono-microbial Gram-negative or fungal infections. Mortality was significantly higher in those who developed VAP (86 vs. 33%, p = 0.002). Our evidence aligned with the available literature in assuming a possible role of SDD in reducing the incidence of VAP in COVID-19 patients, with a possible impact on related mortality and costs

Heat stroke: Clinical experience from an Italian ICU during summer 2015

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Effects of the volume of processed plasma on the outcome, arterial pressure and blood procalcitonin levels in patients with severe sepsis and septic shock treated with coupled plasma filtration and adsorption

To understand how coupled plasma filtration and adsorption (CPFA) could influence the time course of the advanced stages of sepsis, mean arterial pressure (MAP) and norepinephrine dosage. METHODS: Patients with severe sepsis and septic shock with 652 organ failures not responding to volume resuscitation and vasopressor infusion were treated with CPFA within 8 h of admission to the intensive care unit. RESULTS: Thirty-nine patients were treated (median age: 63 years, median SAPS II score: 45) and 28 survived advanced sepsis. In the latter, the median MAP increased and the norepinephrine dosage decreased significantly after CPFA, whereas in the nonsurvivors these values did not change significantly. The volume of treated plasma was significantly higher in survivors than nonsurvivors. CONCLUSION: These results suggest a possible existence of a dose-response effect for CPFA. Future studies are therefore recommended to evaluate the efficacy of this treatment and to determine its best timing and intensit

Regional Citrate Anticoagulation during Coupled Plasma Filtration and Adsorption May Increase Survival in Septic Shock

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Influence of Timing of Initiation and Volume of Processed Plasma on the Outcome of Septic Shock Patients Treated with Coupled Plasma Filtration and Adsorption

The extracorporeal removal of mediators is a rescue strategy for septic shock patients, which is still under investigation. Several techniques are available: coupled plasma filtration and adsorption (CPFA) combines plasma processing with renal replacement therapy