Antibiotic Treatment of Acinetobacter baumannii Superinfection in Patients With SARS-CoV-2 Infection Admitted to Intensive Care Unit: An Observational Retrospective Study.

Introduction: In COVID-19 patients on mechanical ventilation, VAP from Acinetobacter baumannii remains a crucial risk factor for death. Antibiotic resistance represents an important problem in treating this infection. This study aims to describe the evolution of the superinfection from PDR Acinetobacter baumannii in patients with acute respiratory failure from SARS-CoV-2 infection admitted to ICU and compare the impact of two different antibiotic strategies on microbiological negativization. Methods: Single-center observational retrospective study, including patients admitted to our ICU from March 2020 to May 2021 for acute respiratory failure from SARS-CoV-2 infection who developed PDR Acinetobacter baumannii superinfection. Clinical data at ICU admission were collected, as well as the timing of isolation of Acinetobacter baumannii, its resistance profile, the site of infection, and the antibiotic therapy. Results: Of the 32 patients enrolled, 10 patients (31.2%) were treated with the combination of high-dose ampicillin/sulbactam, high-dose tigecycline, intravenous and inhaled colistin (Protocol), the other 22 (68.8%) were treated with the combination of two antibiotics (Control). Of the 10 patients in the Protocol group, 8 patients (80%) received also fosfomycin. All patients (100%) in the Protocol group had microbiological negativization, while in the Control group microbiological negativization was observed in 8 (36.4%) patients, p < 0.01. Conclusion: Our report shows microbiological negativization in all patients treated with the combination therapy of nebulized and intravenous colistin, high-dose tigecycline, and high-dose ampicillin/sulbactam. This combination of antibiotics seems to be a useful alternative when other treatments are not available or fail.

Variation in the Outcome of Norepinephrine-Dependent Septic Patients After the Institution of a Patient-Tailored Therapy Protocol in an Italian Intensive Care Unit: Retrospective Observational Study.

Objective: To evaluate the outcome of patients with septic shock after the institution of a patient tailored therapy protocol in our Intensive Care Unit (ICU). Methods: Single-center retrospective observational study including 100 consecutive septic patients (≥ 16 years) requiring norepinephrine infusion, admitted to our ICU between 2018 and 2019 after the institution of a patient-tailored therapy protocol, compared with a historical control group of 100 patients admitted between 2010 and 2013 (historical controls). The patient-tailored therapy protocol included the use of IgM-enriched immunoglobulins for patients with low plasma IgM levels, blood purification strategies for patients with high plasma levels of cytokines or endotoxin, albumin correction and modulation of vasoactive agents. Clinical and therapeutic parameters were noted at the time of initiation of norepinephrine infusion and for the 1st 24 h. The primary outcome was ICU mortality. Results: ICU-mortality was lower in the patient-tailored therapy cohort as compared to historical controls (32 vs. 57%, p < 0.001). Patient-tailored therapy was associated with a lower risk of ICU-mortality even after adjusting for the main clinical severity indices (adjusted odds ratio 0.331 [95% confidence interval 0.166-0.658], p = 0.002). After propensity score matching, 48 patients in historical control group and 48 patients in the patient-tailored therapy cohort with similar general characteristics were selected. ICU-mortality was lower in the patient-tailored therapy matched subgroup as compared to historical controls (40 vs. 60%, p = 0.037). Conclusions: An individualized therapeutic approach in septic patients may be associated with a survival benefit. However, the use of an historical control group of patients admitted between 2010 and 2013 may introduce substantial bias. Further adequately designed studies are needed to demonstrate the impact of patient-tailored therapy on outcome.

Sublingual microcirculation in patients with SARS-CoV-2 undergoing veno-venous extracorporeal membrane oxygenation.

Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) is a rescue treatment for severe acute respiratory failure refractory to conventional ventilation. We examined the alterations of sublingual microcirculation in patients with SARS-CoV-2 during VV-ECMO treatment and assessed the relationship between microvascular parameters and ventilation, hemodynamics, and laboratory tests. Nine patients were included in the study and the following microcirculatory parameters were estimated: TVD 16.81 (14.46-18.6) mm/mm2; PVD 15.3 (14.09-17.96) mm/mm2; PPV 94.85% (93.82%-97.79%); MFI 2.5 (2.5-2.92); HI 0.4 (0.18-0.4). TVD and PVD were inversely related to D-dimer levels (rho = -0.667, p = 0.05 and rho = -0.733, p = 0.025 respectively), aspartate aminotransferase (AST) (rho = -0.886, p = 0.019 and rho = -0.886, p = 0.019 respectively) and alanine aminotransferase (ALT) (rho = -0.829, p = 0.042 and rho = -0.829, p = 0.042 respectively). Our results showed an altered sublingual microcirculation in patients receiving VV-ECMO for severe SARS-CoV-2 and suggest a potential contribution of endothelia dysfunction to determine microvascular alteration.

Changes in Cytokines, Haemodynamics and Microcirculation in Patients with Sepsis/Septic Shock Undergoing Continuous Renal Replacement Therapy and Blood Purification with CytoSorb.

BACKGROUND: Extracorporeal blood purification therapies have been proposed as a strategy to remove inflammatory mediators during sepsis, thus improving outcome. OBJECTIVES: We aimed to evaluate changes in cytokines, haemodynamics and microcirculation during blood purification with Cytosorb adsorber in septic patients. METHODS: Prospective observational study on critically ill adult patients with sepsis/septic shock underwent renal replacement therapy (RRT) for acute renal failure and haemoadsorption with Cytosorb as adjunctive therapy for 24 h. Measurements were taken at baseline, after 6 and 24 h: haemodynamic parameters, arterial and central venous blood gases, plasma levels of tumour necrosis factor alpha, interleukin (IL) 1-beta, IL-6, IL-8 and IL-10. The sublingual microcirculation was assessed with sidestream dark field videomicroscopy to evaluate the perfused vessel density (PVD) and microvascular flow quality. Tissue oxygenation and microvascular reactivity were assessed with thenar near infrared spectroscopy (NIRS) with a vascular occlusion test. RESULTS: Nine patients; plasma levels of IL-8 decreased at 24 h (p < 0.05 versus 6 h); no significant variation was found for other cytokines. Haemodynamic remained stable throughout the observation. Microvascular perfusion improved over time, with an increase in PVDs at 6 and 24 h (from 13.9 [13.3-16.4] to 15.7 [15-17.3] and 17 [14.8-18.6] mm/mm2 respectively, p = 0.003) and total vessel densities at 24 h (14.9 [13.9-16.9] vs. 17.9 [15.3-20], p = 0.0015). No significant variation was detected in NIRS-derived parameters. The Sequential Organ Failure Assessment score decreased from 12 ± 3 to 10 ± 1 at 24 h (p = 0.039). CONCLUSIONS: In septic patients undergoing RRT, haemoadsorption with Cytosorb seems to determine a decreasing in plasma levels of IL-8, although levels of other cytokines did not vary significantly, and an improvement of microcirculation despite no significant variation in macro-haemodynamics.

IgM-enriched immunoglobulins (Pentaglobin) may improve the microcirculation in sepsis: a pilot randomized trial.

BACKGROUND: Polyclonal or IgM-enriched immunoglobulins may be beneficial during sepsis as an adjuvant immunomodulatory therapy. We aimed to test whether the infusion of IgM-enriched immunoglobulins improves microvascular perfusion during sepsis. METHODS: Single-centre, randomized, double-blind, placebo-controlled phase II trial including adult patients with a diagnosis of sepsis or septic shock for less than 24 h. Patients received an intravenous infusion of 250 mg/kg (5 mL/kg) per day of IgM-enriched immunoglobulins (Pentaglobin, n = 10) for 72 h or placebo (NaCl 0.9%, n = 9). At baseline and after 24 and 72 h of infusion, the sublingual microcirculation was assessed with Incident Dark Field videomicroscopy. Thenar near-infrared spectroscopy (NIRS) was applied with a vascular occlusion test to assess tissue oxygenation and microvascular reactivity. Levels of interleukin (IL) 1-beta, IL-6, IL-8, IL-10 and tumour necrosis factor alpha were measured in the serum. RESULTS: The perfused vessel density (PVD) for small vessels (diameter < 20 micron) increased in the Pentaglobin group (from 21.7 ± 4.7 to 25.5 ± 5.1 mm/mm2) and decreased in the placebo group (from 25 ± 5.8 to 20.7 ± 4.1 mm/mm2, p for interaction < 0.001, two-way analysis of variance). The absolute between-group difference at 72 h was 4.77 (standard error 2.34), p = 0.140. The microvascular flow index for small vessels increased at 24 h in the Pentaglobin group (from 2.68 [2.38-2.78] to 2.93 [2.82-3], p < 0.01) and decreased at 72 h in the placebo group (from 2.83 [2.60-2.97] to 2.67 [2.48-2.73], p < 0.05). Changes in general parameters, cytokines and NIRS-derived parameters were similar between the two groups, except for IL-6 and IL-10 that significantly decreased at 72 h only in the Pentaglobin group. CONCLUSIONS: A 72-h infusion of IgM-enriched immunoglobulins (Pentaglobin) in patients with sepsis or septic shock may be associated with an increase in sublingual microvascular perfusion. Further studies are needed to confirm our findings. Trial registration NCT02655133, www.ClinicalTrials.gov, date of registration 7th January 2016, https://www.clinicaltrials.gov/ct2/show/NCT02655133.

Airway pressure release ventilation during acute hypoxemic respiratory failure: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Airway pressure release ventilation (APRV) has been considered a tempting mode of ventilation during acute respiratory failure within the concept of open lung ventilation. We performed a systematic review and meta-analysis to verify whether adult patients with hypoxemic respiratory failure have a higher number of ventilator-free days at day 28 when ventilated in APRV compared to conventional ventilation strategy. Secondary outcomes were difference in PaO2/FiO2 at day 3, ICU length of stay (LOS), ICU and hospital mortality, mean arterial pressure (MAP), risk of barotrauma and level of sedation. We searched MEDLINE, Scopus and Cochrane Central Register of Controlled Trials database until December 2018. RESULTS: We considered five RCTs for the analysis enrolling a total of 330 patients. For ventilatory-free day at day 28, the overall mean difference (MD) between APRV and conventional ventilation was 6.04 days (95%CI 2.12, 9.96, p = 0.003; I2 = 65%, p = 0.02). Patients treated with APRV had a lower ICU LOS than patients treated with conventional ventilation (MD 3.94 days [95%CI 1.44, 6.45, p = 0.002; I2 = 37%, p = 0.19]) and a lower hospital mortality (RD 0.16 [95%CI 0.02, 0.29, p = 0.03; I2 = 0, p = 0.5]). PaO2/FiO2 at day 3 was not different between the two groups (MD 40.48 mmHg [95%CI - 25.78, 106.73, p = 0.23; I2 = 92%, p < 0.001]). MAP was significantly higher during APRV (MD 5 mmHg [95%CI 1.43, 8.58, p = 0.006; I2 = 0%, p = 0.92]). Then, there was no difference regarding the onset of pneumothorax under the two ventilation strategies (RR 1.94 [95%CI 0.54, 6.94, p = 0.31; I2 = 0%, p = 0.74]). ICU mortality and sedation level were not included into quantitative analysis. CONCLUSION: This study showed a higher number of ventilator-free days at 28 day and a lower hospital mortality in acute hypoxemic patients treated with APRV than conventional ventilation, without any negative hemodynamic impact or higher risk of barotrauma. However, these results need to be interpreted with caution because of the low-quality evidence supporting them and the moderate heterogeneity found. Other well-designed RCTs need to be conducted to confirm our findings.

Association between sublingual microcirculation, tissue perfusion and organ failure in major trauma: A subgroup analysis of a prospective observational study.

INTRODUCTION: Previous studies described impaired microvascular perfusion and tissue oxygenation as reliable predictors of Multiple Organ Failure in major trauma. However, this relationship has been incompletely investigated. The objective of this analysis is to further evaluate the association between organ dysfunction and microcirculation after trauma. MATERIALS AND METHODS: This is a retrospective subgroup analysis on 28 trauma patients enrolled for the Microcirculation DAIly MONitoring in critically ill patients study (NCT 02649088). Patients were divided in two groups according with their Sequential Organ Failure Assessment (SOFA) score at day 4. At admission and every 24 hours, the sublingual microcirculation was evaluated with Sidestream Darkfield Imaging (SDF) and peripheral tissue perfusion was assessed with Near Infrared Spectroscopy (NIRS) and Vascular Occlusion Test (VOT). Simultaneously, hemodynamic, clinical/laboratory parameters and main organ supports were collected. RESULTS: Median SOFA score at Day 4 was 6.5. Accordingly, patients were divided in two groups: D4-SOFA ≤6.5 and D4-SOFA >6.5. The Length of Stay in Intensive Care was significantly higher in patients with D4-SOFA>6.5 compared to D4-SOFA≤6.5 (p = 0.013). Total Vessel Density of small vessels was significantly lower in patients with high D4-SOFA score at Day 1 (p = 0.002) and Day 2 (p = 0.006) after admission; the Perfused Vessel Density was lower in patients with high D4-SOFA score at Day 1 (p = 0.007) and Day 2 (p = 0.033). At Day 1, NIRS monitoring with VOT showed significantly faster tissue oxygen saturation downslope (p = 0.018) and slower upslope (p = 0.04) in patients with high D4-SOFA. DISCUSSION: In our cohort of major traumas, sublingual microcirculation and peripheral microvascular reactivity were significantly more impaired early after trauma in those patients who developed more severe organ dysfunctions. Our data would support the hypothesis that restoration of macrocirculation can be dissociated from restoration of peripheral and tissue perfusion, and that microvascular alterations can be associated with organ failure.

Changes in the sublingual microcirculation following aortic surgery under balanced or total intravenous anaesthesia: a prospective observational study.

BACKGROUND: In vascular surgery with aortic cross-clamping, ischemia/reperfusion injury induces systemic haemodynamic and microcirculatory disturbances. Different anaesthetic regimens may have a varying impact on tissue perfusion. The aim of this study was to explore changes in microvascular perfusion in patients undergoing elective open abdominal aortic aneurysm repair under balanced or total intravenous anaesthesia. METHODS: Prospective observational study. Patients undergoing elective open infrarenal abdominal aortic aneurysm repair received balanced (desflurane + remifentanil, n = 20) or total intravenous anaesthesia (TIVA, propofol + remifentanil using target-controlled infusion, n = 20) according to the clinician's decision. A goal-directed haemodynamic management was applied in all patients. Measurements were obtained before anaesthesia induction (baseline) and at end-surgery and included haemodynamics, arterial/venous blood gases, sublingual microvascular flow and density (incident dark field illumination imaging), peripheral muscle tissue oxygenation and microcirculatory reactivity (thenar near infrared spectroscopy with a vascular occlusion test). RESULTS: The two groups did not differ for baseline characteristics, mean aortic-clamping time and requirement of vasoactive agents during surgery. Changes in mean arterial pressure, systemic vascular resistance index, haemoglobin and blood lactate levels were similar between the two groups, while the cardiac index increased at end-surgery in patients undergoing balanced anaesthesia. The sublingual microcirculation was globally unaltered in the TIVA group at end-surgery, while patients undergoing balanced anaesthesia showed an increase in the total and perfused small vessel densities (from 16.6 ± 4.2 to 19.1 ± 5.4 mm/mm2, p < 0.05). Changes in microvascular density were negatively correlated with changes in the systemic vascular resistance index. The area of reactive hyperaemia during the VOT increased in the balanced anaesthesia group (from 14.8 ± 8.1 to 25.6 ± 14.8%*min, p < 0.05). At end-surgery, the tissue haemoglobin index in the TIVA group was lower than that in the balanced anaesthesia group. CONCLUSIONS: In patients undergoing elective open abdominal aortic aneurysm repair with a goal-directed hemodynamic management, indices of sublingual or peripheral microvascular perfusion/oxygenation were globally preserved with both balanced anaesthesia and TIVA. Patients undergoing balanced anaesthesia showed microvascular recruitment at end-surgery. TRIAL REGISTRATION: NCT03510793 , https://www.clinicaltrials.gov, date of registration April 27th 2018, retrospectively registered.

The impact of a clinical information system in an intensive care unit.

PURPOSE: Although clinical information systems (CISs) have been available and implemented in many Intensive care Units (ICUs) for more than a decade, there is little objective evidence of their impact on the quality of care and staff perceptions. This study was performed to compare time spent charting with pen and paper patient data versus time spent with the new electronic CIS and to evaluate staff perceptions of a CIS in an ICU. MATERIALS AND METHODS: Time spent every day was calculated for each patient, for 7 days, for recording on the paper vital signs and physician therapeutic orders and time spent for computing fluid balance and scores. This time was then compared with time required to make the same activities by means of CIS, 10 months after its introduction in ICU. Four years after the installation of CIS, a questionnaire was given to all staff attending to the ICU to evaluate their opinions of the CIS. RESULTS: The CIS took less staff time to record common ICU data than paper records (3 +/- 2 minutes/day versus 37 +/- 7 minutes/day respectively, P< 0.001). Perceptions of the CIS were that computers promoted an improving charting quality. CONCLUSIONS: The implementation of a CIS was associated with a reduced time spent for daily activity and a positive medical and nursing staff perception.

Initial distribution volume of glucose as noninvasive indicator of cardiac preload: comparison with intrathoracic blood volume.

OBJECTIVE: To analyze the correlation between initial distribution volume of glucose (IDVGI) and intrathoracic blood volume measured by single indicator dilution technique. DESIGN AND SETTING: Prospective clinical study conducted in the intensive care unit of a university hospital. PATIENTS AND METHODS: We enrolled 20 consecutive adult patients requiring hemodynamic monitoring with arterial pulse contour analysis system (PiCCO) and without any underlying pathology inducing generalized protein capillary leakage and/or marked peripheral edema. Cardiac output, intrathoracic blood volume, extravascular lung water were recorded. IDVGI was measured once per day for the first 5 days after PiCCO positioning by administering a bolus of 25 ml 20% glucose (5 g) over 30 s through a central venous catheter. The relationship between IDVGI and other variables was studied by regression analysis. Receiver operating characteristic curves were used to study the relationship between changes in IDVGI and changes in cardiac index, intrathoracic blood volume, and central venous pressure. RESULTS: A good linear correlation was obtained between intrathoracic blood volume and IDVGI ( R(2)=0.79). Receiver operating characteristic curve analysis showed a good ability of initial distribution volume of glucose variations to reflect cardiac index variations. CONCLUSIONS: Our results indicate that IDVGI can serve as noninvasive indicator of cardiac preload.

Noninvasive continuous positive airway pressure delivered by helmet in hematological malignancy patients with hypoxemic acute respiratory failure.

OBJECTIVE: To compare the efficacy of early administration of noninvasive continuous positive airway pressure (nCPAP) delivered by the helmet vs. face mask to treat hematological malignancy patients with fever, pulmonary infiltrates, and hypoxemic acute respiratory failure. DESIGN AND SETTING: Prospective clinical study with historical matched controls in the hematology department of a university hospital. PATIENTS AND INTERVENTIONS: Seventeen hematological malignancy patients with hypoxemic acute respiratory failure defined as: moderate to severe dyspnea, tachypnea (>30-35 breaths/min), use of accessory muscles and paradoxical abdominal motion, and PaO2/FIO2 ratio less than 200. Each patient was treated with nCPAP by helmet outside the ICU in the hematological ward. Arterial oxygen saturation, heart rate, respiratory rate, and blood pressure were monitored to identify early nCPAP failure. Seventeen historical-matched controls treated in the same department with face mask CPAP were selected as control population; matching criteria were age, sex, diagnosis, and PaO2/FIO2 ratio. Primary end-points were improvement in gas exchanges and the need for endotracheal intubation. RESULTS: Oxygenation improved in all patients after nCPAP. No patient failed helmet nCPAP because of intolerance while eigh patients in the mask group did so. nCPAP could be applied continuously for a longer period of time in the helmet group (28.44+/-0.20 vs. 7.5+/-0.45 h). CONCLUSIONS: Early nCPAP with helmet improves oxygenation in selected immunosuppressed patients with hypoxemic acute respiratory failure. Tolerance of helmet nCPAP seems better than that of nCPAP delivered by mask.