Pulmonary volume-feedback and ventilatory pattern after bilateral lung transplantation using neurally adjusted ventilatory assist ventilation.

BACKGROUND: Bilateral lung transplantation results in pulmonary vagal denervation, which potentially alters respiratory drive, volume-feedback, and ventilatory pattern. We hypothesised that Neurally Adjusted Ventilatory Assist (NAVA) ventilation, which is driven by diaphragm electrical activity (EAdi), would reveal whether vagally mediated pulmonary-volume feedback is preserved in the early phases after bilateral lung transplantation. METHODS: We prospectively studied bilateral lung transplant recipients within 48 h of surgery. Subjects were ventilated with NAVA and randomised to receive 3 ventilatory modes (baseline NAVA, 50%, and 150% of baseline NAVA values) and 2 PEEP levels (6 and 12 cm H2O). We recorded airway pressure, flow, and EAdi. RESULTS: We studied 30 subjects (37% female; age: 37 (27-56) yr), of whom 19 (63%) had stable EAdi. The baseline NAVA level was 0.6 (0.2-1.0) cm H2O µV-1. Tripling NAVA level increased the ventilatory peak pressure over PEEP by 6.3 (1.8), 7.6 (2.4), and 8.7 (3.2) cm H2O, at 50%, 100%, and 150% of baseline NAVA level, respectively (P<0.001). EAdi peak decreased by 10.1 (9.0), 9.5 (9.4) and 8.8 µV (8.7) (P<0.001), accompanied by small increases in tidal volume, 8.3 (3.0), 8.7 (3.6), and 8.9 (3.3) ml kg-1 donor's predicted body weight at 50%, 100%, and 150% of baseline NAVA levels, respectively (P<0.001). Doubling PEEP did not affect tidal volume. CONCLUSIONS: NAVA ventilation was feasible in the majority of patients during the early postoperative period after bilateral lung transplantation. Despite surgical vagotomy distal to the bronchial anastomoses, bilateral lung transplant recipients maintained an unmodified respiratory pattern in response to variations in ventilatory assistance and PEEP. CLINICAL TRIAL REGISTRATION: NCT03367221.

COVID-19 multidisciplinary high dependency unit: the Milan model.

COVID-19 is a complex and heterogeneous disease. The pathogenesis and the complications of the disease are not fully elucidated, and increasing evidence shows that SARS-CoV-2 causes a systemic inflammatory disease rather than a pulmonary disease. The management of hospitalized patients in COVID-19 dedicated units is advisable for segregation purpose as well as for infection control. In this article we present the standard operating procedures of our COVID-19 high dependency unit of the Policlinico Hospital, in Milan. Our high dependency unit is based on a multidisciplinary approach. We think that the multidisciplinary involvement of several figures can better identify treatable traits of COVID-19 disease, early identify patients who can quickly deteriorate, particularly patients with multiple comorbidities, and better manage complications related to off-label treatments. Although no generalizable to other hospitals and different healthcare settings, we think that our experience and our point of view can be helpful for countries and hospitals that are now starting to face the COVID-19 outbreak.

Assisted mechanical ventilation promotes recovery of diaphragmatic thickness in critically ill patients: a prospective observational study.

BACKGROUND: Diaphragm atrophy and dysfunction are consequences of mechanical ventilation and are determinants of clinical outcomes. We hypothesize that partial preservation of diaphragm function, such as during assisted modes of ventilation, will restore diaphragm thickness. We also aim to correlate the changes in diaphragm thickness and function to outcomes and clinical factors. METHODS: This is a prospective, multicentre, observational study. Patients mechanically ventilated for more than 48 h in controlled mode and eventually switched to assisted ventilation were enrolled. Diaphragm ultrasound and clinical data collection were performed every 48 h until discharge or death. A threshold of 10% was used to define thinning during controlled and recovery of thickness during assisted ventilation. Patients were also classified based on the level of diaphragm activity during assisted ventilation. We evaluated the association between changes in diaphragm thickness and activity and clinical outcomes and data, such as ventilation parameters. RESULTS: Sixty-two patients ventilated in controlled mode and then switched to the assisted mode of ventilation were enrolled. Diaphragm thickness significantly decreased during controlled ventilation (1.84 ± 0.44 to 1.49 ± 0.37 mm, p < 0.001) and was partially restored during assisted ventilation (1.49 ± 0.37 to 1.75 ± 0.43 mm, p < 0.001). A diaphragm thinning of more than 10% was associated with longer duration of controlled ventilation (10 [5, 15] versus 5 [4, 8.5] days, p = 0.004) and higher PEEP levels (12.6 ± 4 versus 10.4 ± 4 cmH2O, p = 0.034). An increase in diaphragm thickness of more than 10% during assisted ventilation was not associated with any clinical outcome but with lower respiratory rate (16.7 ± 3.2 versus 19.2 ± 4 bpm, p = 0.019) and Rapid Shallow Breathing Index (37 ± 11 versus 44 ± 13, p = 0.029) and with higher Pressure Muscle Index (2 [0.5, 3] versus 0.4 [0, 1.9], p = 0.024). Change in diaphragm thickness was not related to diaphragm function expressed as diaphragm thickening fraction. CONCLUSION: Mode of ventilation affects diaphragm thickness, and preservation of diaphragmatic contraction, as during assisted modes, can partially reverse the muscle atrophy process. Avoiding a strenuous inspiratory work, as measured by Rapid Shallow Breathing Index and Pressure Muscle Index, may help diaphragm thickness restoration.

Effects of Sigh on Regional Lung Strain and Ventilation Heterogeneity in Acute Respiratory Failure Patients Undergoing Assisted Mechanical Ventilation.

OBJECTIVE: In acute respiratory failure patients undergoing pressure support ventilation, a short cyclic recruitment maneuver (Sigh) might induce reaeration of collapsed lung regions, possibly decreasing regional lung strain and improving the homogeneity of ventilation distribution. We aimed to describe the regional effects of different Sigh rates on reaeration, strain, and ventilation heterogeneity, as measured by thoracic electrical impedance tomography. DESIGN: Prospective, randomized, cross-over study. SETTING: General ICU of a single university-affiliated hospital. PATIENTS: We enrolled 20 critically ill patients intubated and mechanically ventilated with PaO2/FIO2 up to 300 mm Hg and positive end-expiratory pressure at least 5 cm H2O (15 with acute respiratory distress syndrome), undergoing pressure support ventilation as per clinical decision. INTERVENTIONS: Sigh was added to pressure support ventilation as a 35 cm H2O continuous positive airway pressure period lasting 3-4 seconds at different rates (no-Sigh vs 0.5, 1, and 2 Sigh(s)/min). All study phases were randomly performed and lasted 20 minutes. MEASUREMENTS AND MAIN RESULTS: In the last minutes of each phase, we measured arterial blood gases, changes in end-expiratory lung volume of nondependent and dependent regions, tidal volume reaching nondependent and dependent lung (Vtnondep and Vtdep), dynamic intratidal ventilation heterogeneity, defined as the average ratio of Vt reaching nondependent/Vt reaching dependent lung regions along inspiration (VtHit). With Sigh, oxygenation improved (p < 0.001 vs no-Sigh), end-expiratory lung volume of nondependent and dependent regions increased (p < 0.01 vs no-Sigh), Vtnondep showed a trend to reduction, and Vtdep significantly decreased (p = 0.11 and p < 0.01 vs no-Sigh, respectively). VtHit decreased only when Sigh was delivered at 0.5/min (p < 0.05 vs no-Sigh), while it did not vary during the other two phases. CONCLUSIONS: Sigh decreases regional lung strain and intratidal ventilation heterogeneity. Our study generates the hypothesis that in ventilated acute respiratory failure patients, Sigh may enhance regional lung protection.

Antibiotics Removal during Continuous Renal Replacement Therapy in Septic Shock Patients: Mixed Modality Versus "Expanded Haemodialysis".

BACKGROUND AND OBJECTIVE: Renal replacement therapy (RRT) plays a critical role in antimicrobial removal, particularly for low-molecular-weight drugs with low plasma protein binding, low distribution volume and hydrophilicity. Medium cut-off (MCO) membranes represent a new generation in dialysis technology, enhancing diffusive modality efficacy and increasing the cut-off from 30 to 45 kDa, crucial for middle molecule removal. This monocentric randomized crossover pilot study aimed to evaluate the impact of continuous haemodialysis with MCO membrane (MCO-CVVHD) on the removal of piperacillin, tazobactam and meropenem compared with continuous veno-venous hemodiafiltration with standard high-flux membrane (HFM-CVVHDF). METHODS: Twenty patients were randomized to undergo MCO-CVVHD followed by HFM-CVVHDF or vice versa. Extraction ratio (ER), effluent clearance (Cleff) and treatment efficiency were assessed at various intervals. Antibiotic nadir plasma levels were measured for both treatment days. RESULTS: HFM-CVVHDF showed greater ER compared with MCO-CVVHD for meropenem (ß = - 8.90 (95% CI - 12.9 to - 4.87), p < 0.001) and tazobactam (ß = - 8.29 (95% CI - 13.5 to - 3.08), p = 0.002) and Cleff for each antibiotic (meropenem ß = - 10,206 (95% CI - 14,787 to - 5787), p = 0.001); tazobactam (ß = - 4551 (95% CI - 7781 to - 1322), p = 0.012); piperacillin (ß = - 3913 (95% CI - 6388 to - 1437), p = 0.002), even if the carryover effect influenced the Cleff for meropenem and tazobactam. No difference was observed in nadir plasma concentrations or efficiency for any antibiotic. Piperacillin (ß = - 38.1 (95% CI - 47.9 to - 28.3), p < 0.001) and tazobactam (ß = - 4.45 (95% CI - 6.17 to - 2.72), p < 0.001) showed lower nadir plasma concentrations the second day compared with the first day, regardless the filter type. CONCLUSION: MCO demonstrated comparable in vivo removal of piperacillin, tazobactam and meropenem to HFM.

Incidence of asymptomatic catheter-related thrombosis in intensive care unit patients: a prospective cohort study.

BACKGROUND: Catheter-related thrombosis (CRT) incidence, rate, and risk factors vary in literature due to differences in populations, catheters, diagnostic methods, and statistical approaches. The aim of this single-center, prospective, observational study was to assess incidence, incidence rate (IR), cumulative incidence, and risk factors by means of IR ratio (IRR) of asymptomatic CRT in a non-oncologic Intensive Care Unit (ICU) population. CRT development was assessed daily by means of ultrasound screening. The proportions of patients and catheters developing CRT and CRT incidence rates, expressed as the number of events per catheter-days (cd), were calculated. Kalbfleisch and Prentice's method was used to estimate the cumulative incidence of CRTs. Univariate and multivariable Poisson regression models were fitted to calculate IRR in risk factors analysis. RESULTS: Fifty (25%, 95% CI 19-31) out of 203 included patients, and 52 (14%, 95% CI 11-18) out of 375 catheters inserted developed CRT [IR 17.7 (13.5-23.2) CRTs/1000*cd], after 5 [3-10] days from insertion. Forty-six CRTs (88%) were partial thrombosis. All CRTs remained asymptomatic. Obesity and ECMO support were patient-related protective factors [IRR 0.24 (0.10-0.60), p = 0.002 and 0.05 (0.01-0.50), p = 0.011, respectively]. The internal jugular vein had higher CRT IR than other sites [20.1 vs. 5.9 CRTs/1000*cd, IRR 4.22 (1.22-14.63), p = 0.023]. Pulmonary artery catheter and left-side cannulation were catheter-related risk factors [IRR 4.24 (2.00-9.00), p < 0.001 vs. central venous catheters; IRR 2.69 (1.45-4.98), p = 0.002 vs. right cannulation, respectively]. No statistically significant effect of the number of simultaneously inserted catheters [IRR 1.11 (0.64-1.94), p = 0.708] and of the catheterization length [IRR 1.09 (0.97-1.22), p = 0.155] was detected. The ICU length of stay was longer in CRT patients (20 [15-31] vs. 6 [4-14] days, p < 0.001), while no difference in mortality was observed. CONCLUSIONS: CRTs are frequent but rarely symptomatic. This study suggests that obesity and ECMO are protective factors, while pulmonary artery catheter, internal jugular vein and left-side positioning are risk factors for CRT.

Effects of positive airway pressure on basilic vein diameter and venous flow velocity in healthy volunteers.

INTRODUCTION: The placement of vascular catheters of adequate size in accordance to catheter-to-vein ratio (CVR) recommendations represents one of the cornerstones of catheter-related upper vein thrombosis prevention. However there is scarcity of data on its effect on the venous dynamics of the basilic vein, a common site for long-term catheter placement. This study investigates the effects of the application of positive airway pressure on the diameter and blood flow velocity of basilic vein. We also measured the effects of under-armpit straps, a device commonly used to keep continuous positive airway pressure (CPAP) helmets in place. METHODS: We enrolled 28 healthy volunteers. Basilic vein diameter and minimum/maximum blood flow velocity, according to respiratory venous flow oscillation, were measured by ultrasound on the midpoint of their dominant arm during spontaneous breathing and during breathing in a CPAP helmet with 10 cm H2O of airway pressure applied, with the helmet kept in place either through armpit straps or by tying the helmet to the bed. RESULTS: The application of 10 cm H2O of positive airway pressure significantly increased basilic vein diameter by 0.9 ± 0.2 mm, while reducing minimum blood flow velocity by 1.8 ± 0.4 cm/s. These effects were amplified by the application of under armpit straps. CONCLUSIONS: Breathing with positive airway pressure increases basilic vein diameter while reducing blood flow-velocity. This phenomenon might lead to an incorrect assessment of CVR, misleading the operator into choosing improperly large catheters.

Ultrasound Versus Computed Tomography for Diaphragmatic Thickness and Skeletal Muscle Index during Mechanical Ventilation.

Background: Diaphragmatic alterations occurring during mechanical ventilation (MV) can be monitored using ultrasound (US). The performance of computed tomography (CT) to evaluate diaphragmatic thickness is limited. Further, the association between muscle mass and outcome is increasingly recognized. However, no data are available on its correlation with diaphragmatic thickness. We aimed to determine correlation and agreement of diaphragmatic thickness between CT and US; and its association with muscle mass and MV parameters. Methods: Prospective observational study. US measurements of the diaphragmatic thickness were collected in patients undergoing MV within 12 h before or after performing a CT scan of the thorax and/or upper abdomen. Data on skeletal muscle index (SMI), baseline, and ventilatory data were recorded and correlated with US and CT measures of diaphragmatic thickness. Agreement was explored between US and CT data. Results: Twenty-nine patients were enrolled and the diaphragm measured by CT resulted overall thicker than US-based measurement of the right hemidiaphragm. The US thickness showed the strongest correlation with the left posterior pillar at CT (r = 0.49, p = 0.008). The duration of the controlled MV was negatively correlated with US thickness (r = -0.45, p = 0.017), the thickness of the right anterior pillar (r = -0.41, p = 0.029), and splenic dome by CT (r = -0.43, p = 0.023). SMI was positively correlated with US diaphragmatic thickness (r = 0.50, p = 0.007) and inversely correlated with the duration of MV before enrollment (r = -0.426, p = 0.027). Conclusions: CT scan of the left posterior pillar can estimate diaphragmatic thickness and is moderately correlated with US measurements. Both techniques show that diaphragm thickness decreases with MV duration. The diaphragmatic thickness by US showed a good correlation with SMI.

Heparin-Free Lung Transplantation on Venovenous Extracorporeal Membrane Oxygenation Bridge.

Extracorporeal membrane oxygenation (ECMO) bridge to lung transplantation (LuTX) exposes the patients to a high risk of perioperative bleeding secondary to systemic anticoagulation and coagulation factors deficiency. With this case series, we propose innovative "no-heparin" management of ECMO-bridge support during LuTX, based upon 1) control heparin resistance with antithrombin III in the preoperative period; 2) relying upon a fully functional, brand new heparinized ECMO circuit; 3) completely avoiding perioperative heparin; 4) hampering fibrinolysis with tranexamic acid; and 5) limiting venoarterial (VA) ECMO escalation, and the following need for full anticoagulation. Following the application of this new approach, we carried out three challenging clinical cases of bilateral ECMO-bridged LuTX effectively, with limited intraoperative blood requirement and no major postoperative bleeding or thromboembolic events. Of note, two of them had an extremely high risk for hemorrhage due to complete right lung anatomic derangement in case number 2 and surgical adhesion following first LuTX in case number 3, while for the case number 1, no blood products were administered during surgery. Despite the limited patient population, such an approach relies on a strong rationale and may be beneficial for managing ECMO bridging to LuTX. Prospective studies are necessary to confirm the validity of our strategy.

Dynamic bedside assessment of the physiologic effects of prone position in acute respiratory distress syndrome patients by electrical impedance tomography.

BACKGROUND: Prone position (PP) improves acute respiratory distress syndrome (ARDS) survival by reducing the risk of ventilation-induced lung injury. However, inter-individual variability is a hallmark of ARDS and lung protection by PP might not be optimal in all patients. In the present study, we dynamically assessed physiologic effects of PP by electrical impedance tomography (EIT) and identified predictors of improved lung protection by PP in ARDS patients. METHODS: Prospective physiologic study on 16 intubated, sedated and paralyzed patients with ARDS undergoing PP as per clinical decision. EIT data were recorded during two consecutive steps: 1) baseline supine position before and after a recruitment maneuver (RM); 2) prone position before and after a RM. "Improved lung protection" by PP was defined in the presence of simultaneous improvement of ventilation homogeneity (Hom), alveolar overdistension and collapse (ODCL) and amount of recruitable lung volume by RM in comparison to supine. RESULTS: PP versus supine increased the tidal volume distending the dependent regions (Vtdep), resulting in improved Hom (1.1±0.9 vs. 1.7±0.9, P=0.021). PP also reduced ODCL (19±9% vs. 28±8%, P=0.005) and increased the recruitable lung volume (80 [71-157] vs. 59 [1-110] mL, P=0.025). "Improved lung protection" by PP was predicted by lower Vtdep, higher Vtndep and poorer Hom measured during baseline supine position (P<0.05). CONCLUSIONS: EIT enables dynamic bedside assessment of the physiologic effects of PP and might support early recognition of ARDS patients more likely to benefit from PP.

Adjuvant treatment of severe varicella pneumonia with intravenous varicella zoster virus-specific immunoglobulins.

Varicella zoster virus (VZV) pneumonia is associated with significant mortality, especially in the immunocompromised host. VZV-specific immunoglobulins (VZIG) are currently used as post-exposure prophylaxis for at-risk patients, but not as adjunctive therapy. A novel case of VZV pneumonia in an immunocompromised patient, treated successfully with intravenous VZIG in combination with acyclovir, is reported here.

Gastrointestinal colonization with multidrug-resistant Gram-negative bacteria during extracorporeal membrane oxygenation: effect on the risk of subsequent infections and impact on patient outcome.

BACKGROUND: In ICU patients, digestive tract colonization by multidrug-resistant (MDR) Gram-negative (G-) bacteria is a significant risk factor for the development of infections. In patients undergoing extracorporeal membrane oxygenation (ECMO), colonization by MDR bacteria and risk of subsequent nosocomial infections (NIs) have not been studied yet. The aim of this study is to evaluate the incidence, etiology, risk factors, impact on outcome of gastrointestinal colonization by MDR G- bacteria, and risk of subsequent infections in patients undergoing ECMO. METHODS: This is a retrospective analysis of prospectively collected data: 105 consecutive patients, treated with ECMO, were admitted to the ICU of an Italian tertiary referral center (San Gerardo Hospital, Monza, Italy) from January 2010 to November 2015. Rectal swabs for MDR G- bacteria were cultured at admission and twice a week. Only colonization and NIs by MDR G- bacteria were analyzed. RESULTS: Ninety-one included patients [48.5 (37-56) years old, 63% male, simplified acute physiology score II 37 (32-47)] underwent peripheral ECMO (87% veno-venous) for medical indications (79% ARDS). Nineteen (21%) patients were colonized by MDR G- bacteria. Male gender (OR 4.03, p = 0.029) and duration of mechanical ventilation (MV) before ECMO > 3 days (OR 3.57, p = 0.014) were associated with increased risk of colonization. Colonized patients had increased odds of infections by the colonizing germs (84% vs. 29%, p < 0.001, OR 12.9), longer ICU length of stay (LOS) (43 vs. 24 days, p = 0.002), MV (50 vs. 22 days, p < 0.001) and ECMO (28 vs. 12 days, p < 0.001), but did not have higher risk of death (survival rate 58% vs. 67%, p = 0.480, OR 0.68). Infected patients had almost halved ICU survival (46% vs. 78%, p < 0.001, OR 4.11). CONCLUSIONS: In patients undergoing ECMO for respiratory and/or circulatory failure, colonization by MDR G- bacteria is frequent and associated with more the tenfold odds for subsequent infection. Those infections are associated with an increased risk of death.

"Extended subcutaneous route" technique: a quick subcutaneous tunnelling technique for PICC insertion.

PURPOSE: To describe a quick tunnelling technique for peripherally inserted central catheter (PICC) insertion called the "extended subcutaneous route" technique. METHODS: The "extended subcutaneous route" technique is described step by step. RESULTS: In 18 consecutive PICCs, inserted with extended route technique in ASST Monza, no complications during insertion were registered. In 969 catheter days observed, we identified only one accidental dislodgement. No other mid-term complications were observed. CONCLUSIONS: Extended subcutaneous route technique allows the creation of a subcutaneous tunnel <5 cm, without skin incision and additional manipulation. Extended subcutaneous route technique may be feasible and useful, particularly for patients with high risk of bleeding or infection.

In vitro evaluation of fluid reflux after flushing different types of needleless connectors.

PURPOSE: To evaluate fluid reflux, when disconnecting syringe, for different needleless connectors. MATERIALS: Nine connectors were tested; 540 measurements were carried out. RESULTS: The connectors tested showed very different performances, about reflux, on disconnection of the syringe used for flushing.The calculated reflux volumes are: Max Zero® - BD: 6.90 (±2.47) mm3; MicroClave Clear® - ICU Medical: 6.14 (±1.46) mm3; Bionecteur® - Vygon: 1.24(±0.73) mm3; Neutron® - ICU Medical: 0.12 (±0.15) mm3; SmartSite® Carefusion: 33.51 (±11.50) mm3; Safe Plus® - Cremascoli: 23.54 (±3.56) mm3; NeutraClear® - Cair: 9.36 (±1.87) mm3; NeutroX® - Cair: 0.33 (±0.31) mm3; Dasa® BTC: 2.38 (±1.67) mm3.Differences between investigated devices were statistically significant (p<0.001). DISCUSSION: It is difficult to establish the best quality-price ratio for needleless connectors. It is important to consider several variable factors: continuous or discontinuous infusion, catheter type, usage environment and caliber of catheter used. It would therefore be useful to have an indication of the intraluminal space potentially affected by blood reflux in relation to a specific device. CONCLUSIONS: Needleless connector is one of the main factors involved in keeping catheter patency. It is important to perform the best choice among the connectors available.An empirical reflux measurement, relative to the needleless connector and the catheter in use, can be obtained using an 18G cannula.