A novel risk score for severe ARDS patients undergoing ECMO after retrieval from peripheral hospitals.

BACKGROUND: Extracorporeal Membrane Oxygenation in severe ARDS unresponsive to conventional protective ventilation is associated with elevated costs, resource and complications, and appropriate risk stratification of candidate patients could be useful to recognize those more likely to benefit from ECMO. We aimed to derive a new outcome prediction score for patients retrieved by our ECMO team from peripheral centers, including systematic echocardiographic evaluation before ECMO start. METHODS: Sixty-nine consecutive patients with refractory ARDS requiring ECMO transferred from peripheral centers to our ICU (a tertiary ECMO referral center), from 1 October 2009 to 31 December 2015, were assessed. RESULTS: All patients were transported on ECMO (distance, median 77, range 4-456 km) The mortality rate was 41% (28/69). Our new risk score included age ≥ 42 years, BMI < 31 kg/m2 , RV dilatation, and pH < 7.35. The proposed cut off (Youden's index method) of nine had a sensitivity of 96% and a specificity of 30% (AUC-ROC: 0.85, 95% CI: 0.76-0.94, P < 0.001). When assessing the discriminatory ability of our risk score in the population of local patients, survivors had a mean value of 15.4 ± 8.6, whereas non-survivors showed a mean value of 20.1 ± 7.4 (P < 0.001). CONCLUSIONS: Our new risk score shows good discriminatory ability both in patients retrieved from peripheral centers and in those implanted at our center. This score includes variables easily available at bedside, and, for the first time, a pathophysiologic element, RV dilatation.

Cerebral microemboli detected by transcranial doppler in patients treated with extracorporeal membrane oxygenation.

INTRODUCTION: Cerebrovascular complications rate in patients treated with extracorporeal membrane oxygenation (ECMO) is about 7%. Ischemic stroke may be caused by solid or gaseous microemboli due to thrombosis within the circuit or cannula. Transcranial Doppler (TCD) is the only method able to detect microembolic signals (MES) in real time. The objective of this study was to detect possible MES by TCD in patients treated with veno-venous (VV) and veno-arterial (VA) ECMO and to test for a relation between the number of MES and the 6-month clinical outcome of these patients. METHODS: This is a monocentric observational prospective study in patients consecutively admitted and treated with ECMO at our regional ECMO referral center in 18 months. TCD detection of MES was performed in patients upon initiation of treatment and then repeated during treatment. RESULTS: Two hundred and forty-eight TCD monitoring were performed in 42 VV and 11 VA ECMO patients. MES were detected in 26.2% of VV ECMO patients and in 81.8% of VA ECMO patients (P < 0.001). In both subgroups of patients, no correlation was found between MES detection and extracorporeal flow velocities or aPTT values. In VA ECMO patients, an inverse correlation between left ventricular ejection fraction and MES grading was found (P = 0.037). In both groups, no clinical neurological impairments correlated to MES detection were found at 6 months follow-up. CONCLUSIONS: MES were found in both ECMO configurations; independently from their pathophysiology, MES do not seem to influence clinical outcome. Multicenter studies are still required with more extensive cases to confirm these results.

Pulmonary vascular dysfunction in refractory acute respiratory distress syndrome before veno-venous extracorporeal membrane oxygenation.

BACKGROUND: Pulmonary vascular dysfunction has been described in patients with acute respiratory distress syndrome (ARDS). Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a well-established treatment for these patients. We hypothesized that severe pulmonary vascular dysfunction and cor pulmonale identified by echocardiography before cannulation in these patients were associated with worse survival. METHODS: Echocardiography was used to identify pulmonary hypertension in 21 patients with refractory ARDS just before ECMO implantation. Survival was compared for those with and without cor pulmonale. RESULTS: In our series, the overall mortality rate was 57.1% (12/21). Echocardiographic exams were transthoracic in 5 patients (23.8%), transesophageal in 4 patients (19%), and both (transthoracic and transesophageal) in the remaining 12 patients (57.1%). In our series, six patients (28.5%) showed LV dysfunction. Acute cor pulmonale was detectable in 2 patients (9.5%), while the remaining 19 patients showed moderate pulmonary dysfunction. Survivors had a higher pre-cannulation LV ejection fraction (EF) (P = 0.02) and tricuspid annular plane excursion (P = 0.04), and lower peak systolic pulmonary artery pressures (P = 0.02). CONCLUSIONS: In patients with refractory ARDS immediately before ECMO implantation, the prevalence of acute cor pulmonale is low (9.5%). Survival is associated with higher LVEF and lower systolic pulmonary arterial pressure. These findings support the idea that echocardiographic assessment of pulmonary artery pressure in patients with refractory ARDS before VV-ECMO implantation may have value for risk-stratification.

The role of extracorporeal membrane oxygenation in donation after circulatory death.

Donor scarcity and the increased need for organ transplantation has prompted the development of an alternative source of donors to the more conventional brain dead donor. While in a Beating-Heart donor, abdominal and intrathoracic organs are perfused, in a non-beating heart donor (NHBD, or DCD), perfusion should be maintained, after confirmation of death, by means of ECMO and inflation of intra-aortic balloon accordingly to the localization of the organs that should be transplanted. In this setting, ECMO allows selective perfusion of the organs which should be transplanted ("compartmental ECMO"). The present review is aimed at summarizing the rationale for ECMO use in organ donation in DCD and the available evidence on this topic, as well as available evidence (in clinical studies) on normothermic organ preservation using ECMO in adults. Despite the fact that available studies suffer from methodological limitations (small cohorts, retrospective analysis, not always comparative), they all reach the same conclusion: the concept of extracorporeal support with oxygenation in DCD seems very promising since it has been reported to increase the available organ supply by approximately 20% to 25%2 by increasing the number of donors by approximately 33%. Centres with ECMO facilities should implement local programmes for donation after cardiac death (both in the emergency department and intensive care) using ECMO taking into account that this technique has been proven to increase donor pool.

HA222 polymorphism in Influenza A(H1N1) 2009 isolates from Intensive Care Units and ambulatory patients during three influenza seasons.

Amino acid substitutions which can affect the receptor binding specificity of the influenza virus, like the substitution of aspartic acid with glycine in position 222 of the haemagglutinin (HA) of influenza virus A(H1N1) 2009, have been associated with increased viral pathogenicity and increased tropism for the lower respiratory tract. In this paper, the polymorphic site 222 and the site 223 of the HA1 polypeptide of H1N1 2009 viruses were analyzed in order to better clarify the role of these substitutions in H1N1 2009 virus virulence. Viral strains included in this study were collected in Tuscany during 3 different influenza seasons from patients with severe as well as with mild forms of influenza caused by A(H1N1) 2009 virus. In addition, the oseltamivir resistance of the H1N1 2009 strains circulating during the same seasons was monitored with the aim to evaluate whether these changes in the HA and in neuraminidase (NA) tend to be linked and to influence each other. Altogether, the results indicate that in severe forms of influenza viral population is more variable than in mild influenza, as regards the site 222. The frequency of such substitutions varied among the three seasons, it was highest in the season 2010-2011 and very low in the season 2012-2013. However these differences were not significant.

Absent SEP during therapeutic hypothermia did not reappear after re-warming in comatose patients following cardiac arrest.

BACKGROUND: Early prediction of neurological outcome for patients resuscitated from cardiac arrest (CA) is a challenging task. Therapeutic hypothermia (TH) has been shown to improve neurological outcome after CA. Two recent studies indicated that somatosensory evoked potentials (SEP) recorded during TH retains high prediction value for poor neurological outcome. It remains unclear whether TH can influence the recovery of bilaterally absent (BA) N20 after re-warming. The primary endpoint of the present study was to evaluate if patients with BA SEPs during TH can recover cortical responses after re-warming. The secondary endpoint was to evaluate whether BA SEPs recorded during TH retains its prediction value for poor neurological outcome as in normothermic patients. METHODS: A single centre prospective cohort study including comatose adults resuscitated from in/out-of-hospital CA treated with TH. SEPs were recorded during TH (6-24 hours after CA) and after re-warming in those patients who remained comatose. Neurological outcome was assessed 6 months after CA using the Glasgow Outcome Scale. RESULTS: Sixty patients were included. In patients with preserved SEP, no significant differences were found between N20 mean amplitude during TH and after re-warming. During TH, 24 patients showed bilaterally absent N20 but none of these recovered cortical responses after re-warming. All patients with absent SEPs during TH did not recover consciousness. CONCLUSIONS: In a single centre cohort of comatose CA patients, our results showed that all patients with absent SEPs during early recording (6-24 hours) during TH showed bilaterally absent SEPs after re-warming. As a secondary result we confirmed previous data that BA SEPs during TH retains its prognostic value for poor neurological outcome, as in normothermic patients.

Vitamin D deficiency in septic patients at ICU admission is not a mortality predictor.

BACKGROUND: Vitamin D is involved in immune regulation in humans. Vitamin D serum deficiency is reported to be common in hospitalized patients, especially among Intensive Care Unit (ICU) patients. Our aim was to evaluate the relationship between vitamin D levels in septic patients and outcome. METHODS: A total of 170 patients were studied, of which 92 were severe sepsis/septic shock patients, and 72 were major trauma patients, as an age-matched control group. Exclusion criteria were: age <18 years (y), malnutrition state, pregnancy, breast feeding, chemotherapy, immunotherapy, pathologies affecting bone and calcium metabolism, vitamin D metabolism derangement for therapy, hematological and solid malignancies, and HIV. Vitamin D levels were measured by radioimmunoassay at admission. RESULTS: Median vitamin D levels at admission to ICU were 10.1 ng/mL in the sepsis group and 18.4 ng/mL in the trauma group (P<0.0001). In univariate analysis, mortality rate in septic patients was significantly correlated with age, gender, SAPS II, vitamin D level at admission, duration of mechanical ventilation, and ICU/hospital length of stay, however, the multivariate logistic regression model confirmed significance only for age. CONCLUSION: In our cohort, septic patients showed a significantly lower vitamin D level than trauma patients in comparison to age cohort patients with the same demographic/clinical characteristics, but no clear relationship between vitamin D level and outcome was found. Further studies with larger samples are needed to clarify the prognostic role of vitamin D and nutraceutical interventions in critically ill patients.

Effects of hemoperfusion with an immobilized polymyxin-B fiber column on cytokine plasma levels in patients with abdominal sepsis.

AIM: The beneficial role of hemofiltration with immobilized polymyxin-B fiber (PMX) columns in sepsis, especially sepsis due to gram-negative bacteria, has previously been emphasized. Although the efficacy of PMX-B fiber-mediated hemofiltration in reducing plasma levels of cytokines has been reported, other studies did not confirm this observation. Here we report the effects of PMX-B fiber-mediated hemofiltration on outcome and cytokine plasma levels in patients with abdominal sepsis. METHODS: Twelve consecutive patients admitted to the Intensive Care Unit (October 2006-December 2007) for severe sepsis/septic shock from abdominal infection were treated with standard therapy and 2 cycles of hemofiltration with PMX cartridges. Clinical data and plasma levels of IL-6, IL-10 and TNF-a were measured 24 hours before and after PMX treatment. RESULTS: Plasma concentrations (pg/mL) of IL-6, IL-10 and TNF-a were significantly lower after hemofiltration with a PMX fiber column (279.9+/-69.2 vs. 130.9+/-18.4, 166.4+/-36.7 vs. 45.5+/-12.2, 83.1+/-13.5 vs. 23.9+/-5.1 pg/mL, respectively; P<0.05). After treatment, patients required lower doses of norepinephrine (0.3+/-0.1 vs. 0.8+/-0.1 mg/kg/min) and reduced lactate levels, recovery of respiratory function and improved Simplified Organ Failure Assessment (SOFA) scores. After 28 days, 6 patients (50%) had survived. Subgroup analysis demonstrated that survivors had higher IL-6 and lower IL-10 and TNF-a pre-treatment plasma levels (pg/mL) compared with deceased patients (324.4+/-41.1 vs.235.3+/-38.4; 98.5+/-16.1 vs. 234.3+/-48.6, 44.5+/-9.0 vs.121.6+/-52.3 pg/mL, respectively; P<0.05). No adverse events imputable to the treatment were recorded. CONCLUSION: Hemofiltration with a PMX fiber column was able to reduce plasma levels of IL-6, IL-10 and TNF-a, especially in patients surviving at 28 days. Use of the technique was associated with lower norepinephrine support and an increased PaO2/FiO2 ratio.

Comparison between single-step and balloon dilatational tracheostomy in intensive care unit: a single-centre, randomized controlled study.

BACKGROUND: Balloon dilatational tracheostomy using the Ciaglia Blue Dolphin device has recently been introduced as a modification of the Ciaglia technique. The aim of this study was to compare the new Dolphin system with the single-step dilatational tracheostomy (Ciaglia Blue Rhino) in intensive care unit (ICU) patients. METHODS: Consecutive patients admitted to the ICU of the Emergency Department (Careggi Teaching Hospital, Florence, Italy) from January 2009 to October 2009, aged >18 years and with an indication for percutaneous dilatational tracheostomy (PDT), were enrolled. Exclusion criteria were infection/injury/malignancy of the neck, thyroid gland hypertrophy, severe head injury with uncontrolled intracranial hypertension, and coagulopathy. Patients were randomly assigned to undergo PDT using either the Ciaglia Blue Rhino (n=35) or the Ciaglia Blue Dolphin technique (n=35). Groups were compared according to tracheal puncture, tracheal tube placement time, procedure-related complications, and bleeding. RESULTS: Baseline clinical data were comparable between the two groups. Median procedure time was significantly shorter in the Rhino group compared with the Dolphin group (1.5 vs 4 min, P = 0.035). The presence of limited intra-tracheal bleeding at bronchoscopy examination after 6 h from PDT was more frequent in the Dolphin group than in the Rhino group patients (68.6% vs 34.3%, respectively, P = 0.008). No major bleeding occurred in either group. CONCLUSIONS: PDT using the Ciaglia Blue Dolphin technique is a feasible and viable option in ICU patients, but the Rhino technique had a shorter execution time and seemed to be associated with fewer tracheal injuries.

Reduction in deep vein thrombosis incidence in intensive care after a clinician education program.

BACKGROUND: Deep vein thrombosis (DVT) is a major complication in intensive care units (ICU) but dedicated guidelines on its management are still lacking. OBJECTIVES AND METHODS: This study investigated the effect of a 1-year educational program for the implementation of DVT prophylaxis on the incidence of inferior limb DVT in a mixed-bed ICU that admits high-risk surgical and trauma patients, investigated during a first retrospective phase [126 patients, SAPS II score 42 (28-54)] and a following prospective phase [264 patients, SAPS II score II 41 (27-55)]. The role of baseline and time-dependent DVT risk factors in DVT occurrence was also investigated during the prospective phase. RESULTS: The educational program on implementation of DVT prophylaxis was associated with a significant decrease in DVT incidence from 11.9% to 4.5% (P < 0.01) and in the mean length of ICU stay (P < 0.01). Combined with pharmacological prophylaxis, the use of elastic compressive stockings significantly also increased in the prospective phase (P < 0.01). The duration of mechanical ventilation, vasopressor administration and neuromuscular block were significantly different between DVT-positive and DVT-negative patients (P < 0.01). Multivariate analysis identified neuromuscular block as the strongest independent predictor for DVT incidence. CONCLUSION: One-year ICU-based educational programs on implementation of DVT prophylaxis were associated with a significant decrease in the incidence of DVT and also in the length of stay in ICU.

The value of lung ultrasound monitoring in H1N1 acute respiratory distress syndrome.

We present the case of a healthy young male who developed acute respiratory failure as a result of infection with influenza A/H1N1 of swine-origin and in whom ventilatory support was optimised and recovery of lung function was monitored by the use of sequential chest ultrasound examinations. The potential pivotal role of bedside lung ultrasonography in H1N1-induced respiratory failure is discussed.

Low-dose dopamine in kidney transplantation.

BACKGROUND: The use of low-dose dopamine (LDD; 0.5-2.5 mug/kg/min) in kidney transplant recipients seeks to increase urine output, prevent arterial vasospasm, and reduce the incidence of acute tubular necrosis. The aim of this study was to evaluate the effect of LDD in the early postoperative period (12 hours) among kidney transplant recipients. METHODS: We studied all kidney transplant recipients admitted to the Intensive Care Unit (ICU) in the early postoperative period from January 2004 to December 2008. A total of 105 patients were retrospectively assigned to two groups: group A (n = 57) was treated with LDD and group B (n = 48), not treated with LDD. All patients otherwise received the same therapy. Blood sample analysis and kidney function were recorded at 0, 6, and 12 hours after admission. For each patient, we collected the following data: donor and transplant kidney features, recipient demographics, intraoperative events, hemodynamic and kidney function parameters in the ICU, and outcomes. Patients were followed for 6 months after ICU discharge. RESULTS: Hourly diuresis and kidney function parameters showed no significant difference between the groups. Significant differences between group A and group B were observed in heart rate (92.63 +/- 14.18 vs 82.87 +/- 13.5, respectively), hours of ICU length of stay (29.0 +/- 17.42 vs 20.43 +/- 7.35, respectively), and 6-month mortality rate (8.8% vs 0%, respectively; P < .05). CONCLUSION: LDD prescription in kidney transplantation neither improved kidney function during the postoperative period nor short-term outcomes, but was associated with an increased heart rate, ICU length of stay and 6-month mortality.

[Antioxidant action of Foy in an experimental model of hypergeneration of oxygen free radicals]. / Azione antiossidante del Foy in un modello sperimentale di ipergenerazione di radicali liberi dell'ossigeno.

BACKGROUND: Several trials have just demonstrated the therapeutic efficacy of gabexate mesylate (Foy). For this drug numerous mechanisms of action have been postulated; protease inhibition, direct or indirect lysosomal membrane stabilization, etc. The aim of this study has been to verify if Foy would express antioxidant properties against free radical overgeneration, responsible for the increase in microvascular permeability which represents one of the most important pathogenetic phenomenon of any condition of shock. A mixture of hypoxanthine-xanthine oxidase has been used to obtain a generation of oxygen free radicals in vivo. METHODS: Experiments were performed on the mesocecum of male Wistar rats; fluorescent labelled bovine albumin has been injected intra-arterially to evaluate the capillary permeability and the mesocecum microcirculation has been observed by fluorescent microscopy. The control group received saline i.v., the second group received topically applied on the mesocecum a mixture of 0.96 mM hypoxanthine and 0.05 UI/ml xanthine oxidase; the third and the fourth groups were pretreated respectively with a topical application and continuous infusion of a Foy 1% solution (50 ml/kg/min). To evaluate capillary permeability and to quantify the degree of extravasation by counting the number of leaky sites, labelled bovine albumin was injected i.a. and mesocecum was observed with fluorescent microscopy for 2 hours. RESULTS AND CONCLUSION: Gabexate mesilate (Foy) exerts its efficacy preventing the increase in capillary permeability provoked by an overgeneration of free radicals; it could express antioxidant properties.

[Antioxidant action of gabexate mesilate (Foy) in an experimental model of endotoxic shock]. / Azione antiossidante del gabesato mesilato (Foy) in un modello sperimentale di shock endotossinico.

BACKGROUND: Circulatory shock, especially endotoxin shock, is characterized by the release of a large number of mediators, among which proteases play a key role. The production of oxygen free radicals into the extracellular space and the increase of capillary permeability is one of the most important consequences of that phenomenon. In order to evaluate the efficacy of gabexate mesilate (Foy) in preventing such increase of microvascular permeability, an experimental model of endotoxin shock was used. MATERIALS AND METHODS: Experiments were performed on the mesocecum of male Wistars rats, fluorescent labeled bovine albumine was injected intrarterially to evaluate the capillary permeability and the mesocecum microcirculation was observed by fluorescent light. The control group received saline i.v.; the II group received a DL 100 of E. coli endotoxin (DIFCO 0111: B4); the III and the IV group received a continuous infusion or topical application of gabexate mesilate respectively, before the administration of endotoxin. To evaluate capillary permeability and to quantify the degree of extravasion by counting the number of leaky sites, fluorescent labelled bovine albumin was injected i.v. and mesocecum was observed with fluorescent microscopy for 2 hours. RESULTS AND CONCLUSIONS: Capillary permeability did not increase in control rats; it largely increased in rats receiving endotoxin i.v. but it did not almost increased in rats receiving gabexate mesilate (Foy) that prevents the increase of capillary permeability that was observed in the group treated with endotoxin alone.