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

BACKGROUND: 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. METHODS: The study aimed to elucidate the role of both timing of initiation and intensity of treatment on the outcome, for which we retrospectively studied 52 patients. We collected the overall pre-CPFA time interval, starting from the first episode of hypotension in the wards and the volume of processed plasma (Vp), which we used as a proxy for intensity of treatment. RESULTS: Timing of initiation did not significantly differ between survivors and non-survivors (25 vs. 27 h), while the Vp did (0.25 vs. 0.17 L/kg/session, p < 0.05). The significance of Vp was confirmed by a multiple logistic regression model. CONCLUSION: Our study confirms that intensity of CPFA, but not its timing of initiation, correlates with survival of septic shock patients.

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.

AIMS: 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 ≥2 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 intensity.

The Techniques of Blood Purification in the Treatment of Sepsis and Other Hyperinflammatory Conditions.

Even in the absence of strong indications deriving from clinical studies, the removal of mediators is increasingly used in septic shock and in other clinical conditions characterized by a hyperinflammatory response. Despite the different underlying mechanisms of action, they are collectively indicated as blood purification techniques. Their main categories include blood- and plasma processing procedures, which can run in a stand-alone mode or, more commonly, in association with a renal replacement treatment. The different techniques and principles of function, the clinical evidence derived from multiple clinical investigations, and the possible side effects are reviewed and discussed along with the persisting uncertainties about their precise role in the therapeutic armamentarium of these syndromes.

The Role of the Intravenous IgA and IgM-Enriched Immunoglobulin Preparation in the Treatment of Sepsis and Septic Shock.

Polyclonal Intravenous Immunoglobulins (IvIg) are often administered to critically ill patients more as an act of faith than on the basis of relevant clinical studies. This particularly applies to the treatment of sepsis and septic shock because the current guidelines recommend against their use despite many investigations that have demonstrated their beneficial effects in different subsets of patients. The biology, mechanisms of action, and clinical experience related to the administration of IvIg are reviewed, which aim to give a more in-depth understanding of their properties in order to clarify their possible indications in sepsis and septic shock patients.

Waterhouse-Friderichsen syndrome following a dog bite in an asplenic patient: case report and review of the literature.

The Waterhouse-Friderichsen syndrome represents a critical condition characterized by a septic shock associated with a disseminated intravascular coagulation causing the plugging of the microvascular network virtually all organs and systems, including the skin, the kidneys, the liver, and adrenal glands; the mortality rate is elevated, and survivors often must undergo multiple limb amputations. Here, we describe the uncommon case of an asplenic patient who developed this syndrome after a superficial wound caused by a dog bite causing an initial infection due to Capnocytophaga canimorsus that is part of the normal oral microbiome of pets. The clinical and pathological findings and the current and future therapeutic options are reviewed and discussed.

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.

Vaccine-induced thrombotic thrombocytopenia is an uncommon complication of COVID-19 vaccines using adenovirus mRNA carriers and has been associated with thrombosis of the cerebral venous sinuses and portal system. We report a case of a 69-year-old woman admitted to the intensive care unit due to stroke caused by thrombosis of the right carotid artery 9 days after receiving the ChAdOx1 nCov-19 vaccine. Further investigations demonstrated multiple thrombi in the arterial tree in the absence of any venous involvement. The clinical course and the treatment are described and discussed.

Effects of the timing and intensity of treatment on septic shock patients treated with CytoSorb®: Clinical experience.

INTRODUCTION: A group of adult septic shock patients treated with hemoperfusion (HA) with the Cytosorb® associated with CVVHD were studied to determine (a) the effects of this technique on different clinical variables; and (b) the impact of the pre CytoSorb® interval and its intensity on the outcome. METHODS: The catecholamine index (CI) and the pressure-catecholamine Index (PCAI) were used to assess the amount of catecholamine administered at baseline and during the procedure, respectively. The pre-treatment time was calculated since the onset of the septic-shock related hypotension and the initiation of the first session and the intensity was assessed considering either the total volume of blood processed and the duration of the HA. RESULTS: Overall, 51 patients with septic shock (30 m, 21 f), age 68 years (IQR 59-76) were retrospectively enrolled in the study; 26 were discharged alive form the ICU (S) and 25 died in ICU (NS); in the S group either CI and PCAI decreased significantly but in NS the CI increased and the PCAI remained stable in NS. In S, the time elapsing from the onset of symptoms and the start of Cytosorb® was shorter than in NS; the duration of the treatment and the volume of blood processed were significantly higher in S than in NS. CONCLUSIONS: In this group of septic shock patients, the earlier initiation of Cytosorb®, its longer duration and the higher volume of blood processed were associated with a better survival.

Effects of tocilizumab versus hemoadsorption combined with tocilizumab in patients with SARS-CoV-2 pneumonia: Preliminary results.

OBJECTIVE: To assess the variations of Interleukin-6 (IL-6) in patients with SARS-CoV-2 infection treated with Tocilizumab (TCZ) alone or in association with hemoadsorption (HA). DESIGN: Retrospective. SETTING: An Intensive Care Unit (ICU) admitting mechanically ventilated patients with SARS-CoV-2 pneumonia. PATIENTS: Four adult patients. INTERVENTIONS: We compared the blood values of IL-6, C-reactive protein (CRP) and of other biochemical variables including the PaO2/FiO2 in two patients who received TCZ alone and in other 2 in whom it was associated with the HA (TCZ-HA) due to the presence of impending or established organ failures other than the lung. All variables were measured before, during and after the treatment. MAIN RESULTS: In all patients, the IL-6 increased during the treatment; after its termination, its values sharply decreased only in those treated also with HA; conversely, the CRP decreased in all patients; the PaO2/FiO2 increased in three patients and remained stable in the remaining one. Both the TCZ and the HA were well tolerated; all patients were weaned from the mechanical ventilation and discharged from the hospital. LIMITATIONS: Although the limited number of patients does not allow to draw firm conclusions, the increase of the IL-6 of can be ascribed to its displacement from cellular and soluble receptors, whereas its decrease is likely due to the scavenging effect exerted by the HA. Although the association TCZ-HA could be valuable in the treatment of the Cytokine Release Storm (CRS) associated with the SARS-CoV-2, the HA could be more effective as it neutralizes a wider panel of inflammatory mediators.

Kinetics of Immunoglobulins in Septic Shock Patients Treated With an IgM- and IgA-Enriched Intravenous Preparation: An Observational Study.

Objective: To assess the variations of the blood levels of immunoglobulins (Ig) in septic shock patients treated with an Ig preparation enriched in IgM and IgA (eIg). Design: The blood levels of Ig in survivors (S) and non-survivors (NS) of a group of septic shock patients were measured before the initial administration (D0) and 1 (D1), 4 (D4), and 7 (D7) days thereafter. The SAPS II score, the capillary permeability, the primary site of infection, the antibiotic appropriateness, and the outcome at 28 days were also assessed. Results: In the interval D0-D7, the IgM increased significantly only in the S while remained stable in NS; the IgA significantly increased in both groups; the IgG did not vary significantly in both groups. At D4, the capillary permeability significantly decreased in S but not in NS. Conclusions: The kinetics of the different classes of Ig after eIg were different between S and NS. This could be related either to (a) different capillary permeability in the two groups or to (b) higher Ig consumption in NS. Further studies to confirm the benefits of eIg in the treatment of sepsis syndrome and to define the specific target population and the correct eIg dose are warranted.

The Combined Use of Tocilizumab and Hemoadsorption in a Patient with SARS-COV-2-19-Associated Pneumonia: A Case Report.

The SARS-COV-2-19-associated respiratory involvement is caused by the massive release of inflammatory cytokines ultimately leading to interstitial pneumonia and acute respiratory distress syndrome (ARDS). In the absence of an effective antiviral treatment, a reasonable causal approach could be constituted by the neutralization of these substances. The authors describe the clinical course of a patient with SARS-COV-2-19 interstitial pneumonia treated with the combination of an anti-interleukin 6 (IL-6) agent (tocilizumab) and hemoadsorption (HA). This combination was used to abate the surge of inflammatory mediators leading to the lung damage. Blood levels of IL-6 and C-reactive protein (CRP) were measured before the initiation of the treatment and in the following 3 days. At the end of the treatment, the values of IL-6 and CRP decreased from 1,040 to 415 pg/mL and from 229 to 59 mg/L, respectively. The gas exchanges and the chest imaging rapidly improved, and the patient was extubated 10 days later. The combination of tocilizumab and HA could be valuable in the treatment of SARS-COV-2-19-associated pneumonia and ARDS that are caused by the release of inflammatory mediators.

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

Following publication of the original article [1], we have been notified that the tagging of the author name was done incorrectly in the XML version of the paper. The correct given name is Michele Claudio, and the family name is Vassallo.

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

The 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.

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 1.003-1.009, 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 1.0006-1.014, 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.

Simple thoracostomy in prehospital trauma management is safe and effective: a 2-year experience by helicopter emergency medical crews.

OBJECTIVE: To evaluate the effectiveness and potential complications of simple thoracostomy, as first described by Deakin, as a method for prehospital treatment of traumatic pneumothorax. METHODS: Prospective observational study of all severe trauma patients rescued by our Regional Helicopter Emergency Medical Service and treated with on-scene simple thoracostomy, over a period of 25 months, from June 1, 2002 to June 30, 2004. RESULTS: Fifty-five consecutive severely injured patients with suspected pneumothorax and an average Revised Trauma Score of 9.6+/-2.7 underwent field simple thoracostomy. Oxygen saturation significantly improved after the procedure (from 86.4+/-10.2% to 98.5%+/-4.7%, P<0.05). No difference exists in the severity of thoracic lesions between patients with systolic arterial pressure and oxygen saturation below and above or equal to 90. A pneumothorax or a haemopneumothorax was found in 91.5% of the cases and a haemothorax in 5.1%. No cases of major bleeding, lung laceration or pleural infection were recorded. No cases of recurrent tension pneumothorax were observed. Forty (72.7%) patients survived to hospital discharge. CONCLUSIONS: Prehospital treatment of traumatic pneumothorax by simple thoracostomy without chest tube insertion is a safe and effective technique.

Relationship between the timing of administration of IgM and IgA enriched immunoglobulins in patients with severe sepsis and septic shock and the outcome: a retrospective analysis.

PURPOSE: Because the use of IgM and IgA enriched polyclonal intravenous immunoglobulins (eIg) is a standard of care in critically ill patients admitted to our intensive care unit (ICU) with the diagnosis of severe sepsis or septic shock, we investigated if the delay from the onset of severe sepsis and septic shock and their administration could influence the outcome. MATERIALS AND METHODS: The medical records of all patients with severe sepsis or septic shock admitted to our ICU from July 2004 through October 2009 and treated with eIg (Pentaglobin®; Biotest, Dreieich, Germany) were retrospectively examined. RESULTS: A total of 129 adult patients with severe sepsis or septic shock were considered eligible. Thirty-two percent of patients died during the ICU stay. Survivors were given eIg significantly earlier than nonsurvivors (23 vs 63 hours, P < .05). The delay in the administration of eIg and the Simplified Acute Physiology Score II were the only variables that entered stepwise a propensity score-adjusted logistic model. The delay in the administration of eIg was a significant predictor of the odds of dying during the ICU stay (odds ratio for 1 hour of delay, 1.007; P < .01; 99% confidence interval from 1.001 to 1.010) and proved to be independent from the Simplified Acute Physiology Score II and other variables. CONCLUSIONS: The efficacy of eIg, being maximal in early phases of severe sepsis and/or septic shock, is probably time dependent.