Intravenous immunoglobulin in septic shock: review of the mechanisms of action and meta-analysis of the clinical effectiveness

Sepsis is characterized by a complex immune response. In this study we aimed to provide a review of the mechanisms of action of immunoglobulin (Ig) related to sepsis and an updated meta-analysis of the clinical effectiveness of the Ig use in septic patients

Exploring alternative routes for oxygen administration

none5siHypoxemia may compromise cell metabolism and organ function. Supplemental oxygen (O2) at high concentrations may prove ineffective, and issues relating to hyperoxia, barotrauma, mechanical ventilation, and extracorporeal oxygenation are well documented. Old reports suggest the potential safety and efficacy of alternative routes for O2 administration, such as intravenous or intestinal. We re-explored these routes in rat models of hypoxemia.Damiani, Elisa; Dyson, Alex; Zacchetti, Lucia; Donati, Abele; Singer, MervynDamiani, Elisa; Dyson, Alex; Zacchetti, Lucia; Donati, Abele; Singer, Mervy

Airway Ultrasound as Predictor of Difficult Direct Laryngoscopy: A Systematic Review and Meta-analysis

Background: Despite several clinical index tests that are currently applied for airway assessment, unpredicted difficult laryngoscopy may still represent a serious problem in anesthesia practice. The aim of this systematic review and meta-analysis was to evaluate whether preoperative airway ultrasound can predict difficult direct laryngoscopy in adult patients undergoing elective surgery under general anesthesia. Methods: We searched the Medline, Scopus, and Web of Science databases from their inception to December 2020. The population of interest included adults who required tracheal intubation for elective surgery under general anesthesia without clear anatomical abnormalities suggesting difficult laryngoscopy. A bivariate model has been used to assess the accuracy of each ultrasound index test to predict difficult direct laryngoscopy. Results: Fifteen studies have been considered for quantitative analysis of summary receiver operating characteristic (SROC). The sensitivity for distance from skin to epiglottis (DSE), distance from skin to hyoid bone (DSHB), and distance from skin to vocal cords (DSVC) was 0.82 (0.74-0.87), 0.71 (0.58-0.82), and 0.75 (0.62-0.84), respectively. The specificity for DSE, DSHB, and DSVC was 0.79 (0.70-0.87), 0.71 (0.57-0.82), and 0.72 (0.45-0.89), respectively. The area under the curve (AUC) for DSE, DSHB, DSVC, and ratio between the depth of the pre-epiglottic space and the distance from the epiglottis to the vocal cords (Pre-E/E-VC) was 0.87 (0.84-0.90), 0.77 (0.73-0.81), 0.78 (0.74-0.81), and 0.71 (0.67-0.75), respectively. Patients with difficult direct laryngoscopy have higher DSE, DSVC, and DSHB values than patients with easy laryngoscopy, with a mean difference of 0.38 cm (95% confidence interval [CI], 0.17-0.58 cm; P = .0004), 0.18 cm (95% CI, 0.01-0.35 cm; P = .04), and 0.23 cm (95% CI, 0.08-0.39 cm; P = .004), respectively. Conclusions: Our study demonstrates that airway ultrasound index tests are significantly different between patients with easy versus difficult direct laryngoscopy, and the DSE is the most studied index test in literature to predict difficult direct laryngoscopy. However, it is not currently possible to reach a definitive conclusion. Further studies are needed with better standardization of ultrasound assessment to limit all possible sources of heterogeneity

Microcirculation-guided resuscitation in sepsis: the next frontier?

Microcirculatory dysfunction plays a key role in the pathogenesis of tissue dysoxia and organ failure in sepsis. Sublingual videomicroscopy techniques enable the real-time non-invasive assessment of microvascular blood flow. Alterations in sublingual microvascular perfusion were detected during sepsis and are associated with poor outcome. More importantly, sublingual videomicroscopy allowed to explore the effects of commonly applied resuscitative treatments in septic shock, such as fluids, vasopressors and inotropes, and showed that the optimization of macro-hemodynamic parameters may not be accompanied by an improvement in microvascular perfusion. This loss of "hemodynamic coherence," i.e., the concordance between the response of the macrocirculation and the microcirculation, advocates for the integration of microvascular monitoring in the management of septic patients. Nonetheless, important barriers remain for a widespread use of sublingual videomicroscopy in the clinical practice. In this review, we discuss the actual limitations of this technique and future developments that may allow an easier and faster evaluation of the microcirculation at the bedside, and propose a role for sublingual microvascular monitoring in guiding and titrating resuscitative therapies in sepsis

Acute Kidney Injury and Fluid Resuscitation in Septic Patients: Are We Protecting the Kidney?

Acute kidney injury (AKI) is a common complication in critically ill patients, especially among septic patients. Sepsis and hypovolemia are the 2 most frequent etiologies of AKI in intensive care units and frequently coexist in critically ill patients. Effective fluid resuscitation is crucial for the stabilization of sepsis-induced tissue hypoperfusion or septic shock. However, the lack of a goal-directed therapy targeting kidney oxygenation prevents from optimization of the fluid therapy with regard to improvement of renal oxygen delivery and extraction. Similarly, fluid administration as all therapeutic actions carries adverse effects such as the activation of cytokines, disruption of the capillary glycocalyx, and adverse effects on kidney metabolism and oxygenation. Moreover, a positive fluid balance is associated with an increased risk of AKI and is a negative predictor for recovery of renal function. The role of fluid resuscitation on kidney injury stems from the high renal vulnerability to hypoxemic injury. Indeed, fluids have a poor oxygen solubility and hemodilution decreases blood viscosity both promoting intrarenal shunting and heterogeneity with a decreased capillary density and enhanced intrarenal cortex and medullary hypoxia. The development of physiological biomarkers that are able to detect the early development of AKI specifically aimed at the identification of renal microcirculatory dysfunctions should form a valuable contribution to monitoring therapeutic modalities

Effect of performance improvement programs on compliance with sepsis bundles and mortality: a systematic review and meta-analysis of observational studies

none8noSeveral reports suggest that implementation of the Surviving Sepsis Campaign (SSC) guidelines is associated with mortality reduction in sepsis. However, adherence to the guideline-based resuscitation and management sepsis bundles is still poor.Damiani, Elisa; Donati, Abele; Serafini, Giulia; Rinaldi, Laura; Adrario, Erica; Pelaia, Paolo; Busani, Stefano; Girardis, MassimoDamiani, Elisa; Donati, Abele; Serafini, Giulia; Rinaldi, Laura; Adrario, Erica; Pelaia, Paolo; Busani, Stefano; Girardis, Massim

Goal-directed Intraoperative therapy reduces morbidity and length of hospital stay in high-risk surgical patients

Abstract: Background: Postoperative organ failures commonly occur after major abdominal surgery, increasing the utilization of resources and costs of care. Tissue hypoxia is a key trigger of organ dysfunction. A therapeutic strategy designed to detect and reverse tissue hypoxia, as diagnosed by an increase of oxygen extraction (0,ER) over a predefined threshold, could decrease the incidence of organ failures. The primary aim of this study was to compare the number of patients with postoperative organ failure and length of hospital stay between those randomized to conventional vs a protocolized strategy designed to maintain O2ER < 27%. Methods: A prospective, randomized, controlled trial was performed in nine hospitals in Italy. One hundred thirty-five high-risk patients scheduled for major abdominal surgery were randomized in two groups. All patients were managed to achieve standard goals: mean arterial pressure > 80 mm Hg and urinary output > 0.5 mL/kg/h. The patients of the "pr..

Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial

Despite suggestions of potential harm from unnecessary oxygen therapy, critically ill patients spend substantial periods in a hyperoxemic state. A strategy of controlled arterial oxygenation is thus rational but has not been validated in clinical practice

Recombinant activated protein C treatment improves tissue perfusion and oxygenation in septic patients measured by near-infrared spectroscopy

INTRODUCTION: The purpose was to test the hypothesis that muscle perfusion, oxygenation, and microvascular reactivity would improve in patients with severe sepsis or septic shock during treatment with recombinant activated protein C (rh-aPC) (n = 11) and to explore whether these parameters are related to macrohemodynamic indices, metabolic status or Sequential Organ Failure Assessment (SOFA) score. Patients with contraindications to rh-aPC were used as a control group (n = 5). MATERIALS AND METHODS: Patients were sedated, intubated, mechanically ventilated, and hemodynamically monitored with the PiCCO system. Tissue oxygen saturation (StO2) was measured using near-infrared spectroscopy (NIRS) during the vascular occlusion test (VOT). Baseline StO2 (StO2 baseline), rate of decrease in StO2 during VOT (StO2 downslope), and rate of increase in StO2 during the reperfusion phase were (StO2 upslope) determined. Data were collected before (T0), during (24 hours (T1a), 48 hours (T1b), 72 hours (T1c) and 96 hours (T1d)) and 6 hours after stopping rh-aPC treatment (T2) and at the same times in the controls. At every assessment, hemodynamic and metabolic parameters were registered and the SOFA score calculated. RESULTS: The mean +/- standard deviation Acute Physiology and Chronic Health Evaluation II score was 26.3 +/- 6.6 and 28.6 +/- 5.3 in rh-aPC and control groups, respectively. There were no significant differences in macrohemodynamic parameters between the groups at all the time points. In the rh-aPC group, base excess was corrected (P < 0.01) from T1a until T2, and blood lactate was significantly decreased at T1d and T2 (2.8 +/- 1.3 vs. 1.9 +/- 0.7 mmol/l; P < 0.05). In the control group, base excess was significantly corrected at T1a, T1b, T1c, and T2 (P < 0.05). The SOFA score was significantly lower in the rh-aPC group compared with the controls at T2 (7.9 +/- 2.2 vs. 12.2 +/- 3.2; P < 0.05). There were no differences between groups in StO2 baseline. StO2 downslope in the rh-aPC group decreased significantly at all the time points, and at T1b and T2 (-16.5 +/- 11.8 vs. -8.1 +/- 2.4%/minute) was significantly steeper than in the control group. StO2 upslope increased and was higher than in the control group at T1c, T1d and T2 (101.1 +/- 62.1 vs. 54.5 +/- 23.8%/minute) (P < 0.05). CONCLUSIONS: Treatment with rh-aPC may improve muscle oxygenation (StO2 baseline) and reperfusion (StO2 upslope) and, furthermore, rh-aPC treatment may increase tissue metabolism (StO2 downslope). NIRS is a simple, real-time, non-invasive technique that could be used to monitor the effects of rh-aPC therapy at microcirculatory level in septic patient

Effects of the Infusion of 4% or 20% Human Serum Albumin on the Skeletal Muscle Microcirculation in Endotoxemic Rats

Sepsis-induced microcirculatory alterations contribute to tissue hypoxia and organ dysfunction. In addition to its plasma volume expanding activity, human serum albumin (HSA) has anti-oxidant and anti-inflammatory properties and may have a protective role in the microcirculation during sepsis. The concentration of HSA infused may influence these effects. We compared the microcirculatory effects of the infusion of 4% and 20% HSA in an experimental model of sepsis