Mauro Panigada

Positive End-expiratory Pressure Improves Respiratory Function in Obese but not in Normal Subjects during Anesthesia and Paralysis

BACKGROUND Morbidly obese patients, during anesthesia and paralysis, experience more severe impairment of respiratory mechanics and gas exchange than normal subjects. The authors hypothesized that positive end-expiratory pressure (PEEP) induces different responses in normal subjects (n = 9; body mass index < 25 kg/m2) versus obese patients (n = 9; body mass index > 40 kg/m2). METHODS The authors measured lung volumes (helium technique), the elastances of the respiratory system, lung, and chest wall, the pressure-volume curves (occlusion technique and esophageal balloon), and the intraabdominal pressure (intrabladder catheter) at PEEP 0 and 10 cm H2O in paralyzed, anesthetized postoperative patients in the intensive care unit or operating room after abdominal surgery. RESULTS At PEEP 0 cm H2O, obese patients had lower lung volume (0.59 +/- 0.17 vs. 2.15 +/- 0.58 l [mean +/- SD], P < 0.01); higher elastances of the respiratory system (26.8 +/- 4.2 vs. 16.4 +/- 3.6 cm H2O/l, P < 0.01), lung (17.4 +/- 4.5 vs. 10.3 +/- 3.2 cm H2O/l, P < 0.01), and chest wall (9.4 +/- 3.0 vs. 6.1 +/- 1.4 cm H2O/l, P < 0.01); and higher intraabdominal pressure (18.8 +/-7.8 vs. 9.0 +/- 2.4 cm H2O, P < 0.01) than normal subjects. The arterial oxygen tension was significantly lower (110 +/- 30 vs. 218 +/- 47 mmHg, P < 0.01; inspired oxygen fraction = 50%), and the arterial carbon dioxide tension significantly higher (37.8 +/- 6.8 vs. 28.4 +/- 3.1, P < 0.01) in obese patients compared with normal subjects. Increasing PEEP to 10 cm H2O significantly reduced elastances of the respiratory system, lung, and chest wall in obese patients but not in normal subjects. The pressure-volume curves were shifted upward and to the left in obese patients but were unchanged in normal subjects. The oxygenation increased with PEEP in obese patients (from 110 +/-30 to 130 +/- 28 mmHg, P < 0.01) but was unchanged in normal subjects. The oxygenation changes were significantly correlated with alveolar recruitment (r = 0.81, P < 0.01). CONCLUSIONS During anesthesia and paralysis, PEEP improves respiratory function in morbidly obese patients but not in normal subjects.

Evaluation of continuous aspiration of subglottic secretion in an in vivo study

Objective:Continuous aspiration of subglottic secretions (CASS) is believed to lower the incidence of ventilator-associated pneumonia. Animal studies to establish safety and efficacy of CASS have not been conducted. Design:Prospective randomized animal study. Setting:Animal-research facility at the U.S. National Institutes of Health. Subjects:Twenty-two sheep. Interventions:Sheep were randomized into three groups. In group C (control), eight sheep were kept prone, intubated with a standard endotracheal tube (ETT), and mechanically ventilated for 72 hrs with head and ETT elevated at an angle of 30°. In group CASS-HU (CASS, head up), seven sheep were managed as group C and intubated with a Hi-Lo Evac, Mallinckrodt ETT (CASS suction kept at ≤20 mm Hg). In group CASS-HD (CASS, head down), seven sheep were kept prone with CASS, and the ETT and trachea were horizontal to promote spontaneous drainage of mucus from the ETT. Measurements and results:The lower respiratory tract in the CASS-HU group was heavily colonized in all seven sheep (median 4.6 × 109, range, 1.5 × 108 to 7.9 × 109 colony-forming units/g), with a reduction of lung bacterial colonization compared with the C group (p = .05). In group CASS-HD, the lower respiratory tract was not colonized in six of seven sheep. One sheep showed low levels of bacterial growth (median, 0; range, 0–2.2 × 105). At autopsy, in all 14 sheep with CASS, we found tracheal mucosal injury of different degrees of severity at the level of the suction port of the ETT. Conclusions:In group CASS-HU, regardless of finding a marginal decrease of the bacterial colonization of the lower airways, there was pervasive trachea-bronchial-lung bacterial colonization. Second, there was minimal, or absent, bacterial colonization when the orientation of the CASS ETT was at, or just below, horizontal. Third, there was widespread injury to tracheal mucosa/submucosa from the use of CASS. Note that results of studies conducted in an animal model are always difficult to extrapolate to the clinical practice due to anatomical and functional differences.

Effects of different continuous positive airway pressure devices and periodic hyperinflations on respiratory function.

ObjectiveTo compare the effect on respiratory function of different continuous positive airway pressure systems and periodic hyperinflations in patients with respiratory failure. DesignProspective SettingHospital intensive care unit. PatientsSixteen intubated patients (eight men and eight women, age 54 ± 18 yrs, Pao2/Fio2 277 ± 58 torr, positive end-expiratory pressure 6.2 ± 2.0 cm H2O). InterventionsWe evaluated continuous flow positive airway pressure systems with high or low flow plus a reservoir bag equipped with spring-loaded mechanical or underwater seal positive end-expiratory pressure valve and a continuous positive airway pressure by a Servo 300 C ventilator with or without periodic hyperinflations (three assisted breaths per minute with constant inspiratory pressure of 30 cm H2O over positive end-expiratory pressure). Measurements and Main Results We measured the respiratory pattern, work of breathing, dyspnea sensation, end-expiratory lung volume, and gas exchange. We found the following: a) Work of breathing and gas exchange were comparable between continuous flow systems; b) the ventilator continuous positive airway pressure was not different compared with continuous flow systems; and c) continuous positive airway pressure with periodic hyperinflations reduced work of breathing (10.7 ± 9.5 vs. 6.3 ± 5.7 J/min, p < .05) and dyspnea sensation (1.6 ± 1.2 vs. 1.1 ± 0.8 cm, p < .05) increased end-expiratory lung volume (1.6 ± 0.8 vs. 2.0 ± 0.9 L, p < .05) and Pao2 (100 ± 21 vs. 120 ± 25 torr, p < .05) compared with ventilator continuous positive airway pressure. ConclusionsThe continuous flow positive airway pressure systems tested are equally efficient; a ventilator can provide satisfactory continuous positive airway pressure; and the use of periodic hyperinflations during continuous positive airway pressure can improve respiratory function and reduce the work of breathing.

Simulation-Based Training of Extracorporeal Membrane Oxygenation During H1N1 Influenza Pandemic: The Italian Experience

&NA; On November 2009, the Italian health authorities set up a network of selected intensive care unit (ICU) centers (ECMOnet) to prepare for the treatment of the sickest patients of influenza A (H1N1) by means of extracorporeal membrane oxygenation (ECMO). To quickly and efficaciously train all the physicians working in the ICUs of the ECMOnet on ECMO use, we decided to take advantages of the opportunity provided by simulation technology. Simulation proved efficacious in providing adequate training and education to participants as confirmed by the survival results obtained by the group of ICUs of the ECMOnet. Our experience supports the use of simulation as a valuable alternative to animal laboratory sessions proposed by traditional ECMO training programs providing participants with cognitive, technical, and behavioral skills and allowing a proficient transfer of those skills to the real medical domain.

Assessment of Fibrinolysis in Sepsis Patients with Urokinase Modified Thromboelastography

Introduction Impairment of fibrinolysis during sepsis is associated with worse outcome. Early identification of this condition could be of interest. The aim of this study was to evaluate whether a modified point-of-care viscoelastic hemostatic assay can detect sepsis-induced impairment of fibrinolysis and to correlate impaired fibrinolysis with morbidity and mortality. Methods This single center observational prospective pilot study was performed in an adult Intensive Care Unit (ICU) of a tertiary academic hospital. Forty consecutive patients admitted to the ICU with severe sepsis or septic shock were included. Forty healthy individuals served as controls. We modified conventional kaolin activated thromboelastography (TEG) adding urokinase to improve assessment of fibrinolysis in real time (UK-TEG). TEG, UK-TEG, plasminogen activator inhibitor (PAI)-1, thrombin-activatable fibrinolysis inhibitor (TAFI), d-dimer, DIC scores and morbidity (rated with the SOFA score) were measured upon ICU admission. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) of mortality at ICU discharge. Results UK-TEG revealed a greater impairment of fibrinolysis in sepsis patients compared to healthy individuals confirmed by PAI-1. TAFI was not different between sepsis patients and healthy individuals. 18/40 sepsis patients had fibrinolysis impaired according to UK-TEG and showed higher SOFA score (8 (6–13) vs 5 (4–7), p = 0.03), higher mortality (39% vs 5%, p = 0.01) and greater markers of cellular damage (lactate levels, LDH and bilirubin). Mortality at ICU discharge was predicted by the degree of fibrinolysis impairment measured by UK-TEG Ly30 (%) parameter (OR 0.95, 95% CI 0.93–0.98, p = 0.003). Conclusions Sepsis-induced impairment of fibrinolysis detected at UK-TEG was associated with increased markers of cellular damage, morbidity and mortality.

Comparison between clinical indicators of transmembrane oxygenator thrombosis and multidetector computed tomographic analysis

This study aims to assess whether multidetector computed tomography (MDCT) could accurately confirm the clinical suspicion of transmembrane oxygenator thrombosis (MOT) during extracorporeal membrane oxygenation (ECMO). Twenty-seven oxygenators were examined using MDCT at the end of patient treatment. Transmembrane oxygenator thrombosis was suspected in 15 of them according to the presence of at least 2 of the following clinical indicators: (1) increase in d-dimer, (2) decrease in platelet count, (3) decrease in oxygenator performance, and (4) presence of clots on the surface of the oxygenator. Transmembrane oxygenator thrombosis was confirmed by MDCT in 5 (33%) of them. Transmembrane oxygenator thrombosis was unexpectedly found in 5 (41%) of the remaining 12 oxygenators not suspected for MOT. Eight (80%) of these oxygenators had clots accounting for less than 1% of total volume. Clots were mainly detectable at the apical corner of the oxygenator, most likely due to greater blood stasis. We found a significant increase in d-dimer and in membrane oxygenator shunt and a decrease in platelet count from the start to the discontinuation of ECMO. Hemostatic abnormalities significantly reverted 48 hours after oxygenator removal, suggesting the role of ECMO in activation of the coagulation cascade. Multidetector computed tomographic scan could not accurately confirm the clinical suspicion of MOT.

Prevalence Of "Flat-Line" Thromboelastography During Extracorporeal Membrane Oxygenation For Respiratory Failure In Adults

We evaluated the prevalence of a thromboelastography reaction time (R time) >90 min (“flat-line”) reversible with heparinase during extracorporeal membrane oxygenation (ECMO). We evaluated the association between “flat-line” thromboelastography, other coagulation tests, and risk of bleeding during ECMO. Thirty-two consecutive patients on ECMO were included. Anticoagulation was provided by continuous infusion of unfractionated heparin to maintain an activated partial thromboplastin time (aPTT) ratio between 1.5 and 2.0. Activated clotting times (ACTs) thromboelastography without and with heparinase were measured. Occurrence of bleeding was recorded. Median heparin infusion rate was 16 (12–20) IU/kg/h, aPTT ratio was 1.67 (1.48–1.96), and ACT was 173 (161–184) sec. One hundred forty-five (46%) of 316 paired thromboelastography samples were “flat lines” all reversed with heparinase. Patients with “flat-line” thromboelastography received more heparin (p = 0.001) but had similar platelet count (p = 0.164) and fibrinogen level (p = 0.952) than those without. Activated partial thromboplastin time, ACT, and R time without heparinase weakly correlated between each other (Spearman correlation ⩽0.36) with poor agreement (Cohen’s &kgr; ⩽0.10). Major bleeding occurred in seven (22%) patients. Bleeding during ECMO was not predicted by any of the used test. In conclusion, adjusting heparin infusion to maintain aPTT ratio between 1.5 and 2.0 frequently resulted in “flat-line” thromboelastography.

The delicate balance between pro-(risk of thrombosis) and anti-(risk of bleeding) coagulation during extracorporeal membrane oxygenation

During veno-venous extracorporeal membrane oxygenation (VV-ECMO), a pump drains blood from a large vein, moves it towards a membrane oxygenator, where gas exchange occurs, and then pushes it back into a large vein (1). Blood is thus continuously exposed to non-biological surfaces, including cannulas and membrane oxygenator, and high shear stress, mainly generated by the pump. Platelets and coagulation are activated so that systemic anticoagulation is needed to prevent thrombosis, inside and outside the body.

Effects of sodium citrate, citric acid and lactic acid on human blood coagulation

Introduction: Citric acid infusion in extracorporeal blood may allow concurrent regional anticoagulation and enhancement of extracorporeal CO2 removal. Effects of citric acid on human blood thromboelastography and aggregometry have never been tested before. Methods: In this in vitro study, citric acid, sodium citrate and lactic acid were added to venous blood from seven healthy donors, obtaining concentrations of 9 mEq/L, 12 mEq/L and 15 mEq/L. We measured gas analyses, ionized calcium (iCa++) concentration, activated clotting time (ACT), thromboelastography and multiplate aggregometry. Repeated measure analysis of variance was used to compare the acidifying and anticoagulant properties of the three compounds. Results: Sodium citrate did not affect the blood gas analysis. Increasing doses of citric and lactic acid progressively reduced pH and HCO3− and increased pCO2 (p<0.001). Sodium citrate and citric acid similarly reduced iCa++, from 0.39 (0.36-0.39) and 0.35 (0.33-0.36) mmol/L, respectively, at 9 mEq/L to 0.20 (0.20-0.21) and 0.21 (0.20-0.23) mmol/L at 15 mEq/L (p<0.001). Lactic acid did not affect iCa++ (p=0.07). Sodium citrate and citric acid similarly incremented the ACT, from 234 (208-296) and 202 (178-238) sec, respectively, at 9 mEq/L, to >600 sec at 15 mEq/L (p<0.001). Lactic acid did not affect the ACT values (p=0.486). Sodium citrate and citric acid similarly incremented R-time and reduced α-angle and maximum amplitude (MA) (p<0.001), leading to flat-line thromboelastograms at 15 mEq/L. Platelet aggregometry was not altered by any of the three compounds. Conclusions: Citric acid infusions determine acidification and anticoagulation of blood similar to lactic acid and sodium citrate, respectively.

Intensive care unit patients with lower respiratory tract nosocomial infections: The ENIRRIs project

The clinical course of intensive care unit (ICU) patients may be complicated by a large spectrum of lower respiratory tract infections (LRTI), defined by specific epidemiological, clinical and microbiological aspects. A European network for ICU-related respiratory infections (ENIRRIs), supported by the European Respiratory Society, has been recently established, with the aim at studying all respiratory tract infective episodes except community-acquired ones. A multicentre, observational study is in progress, enrolling more than 1000 patients fulfilling the clinical, biochemical and radiological findings consistent with a LRTI. This article describes the methodology of this study. A specific interest is the clinical impact of non-ICU-acquired nosocomial pneumonia requiring ICU admission, non-ventilator-associated LRTIs occurring in the ICU, and ventilator-associated tracheobronchitis. The clinical meaning of microbiologically negative infectious episodes and specific details on antibiotic administration modalities, dosages and duration are also highlighted. Recently released guidelines address many unresolved questions which might be answered by such large-scale observational investigations. In light of the paucity of data regarding such topics, new interesting information is expected to be obtained from our network research activities, contributing to optimisation of care for critically ill patients in the ICU. Methodology for the first European network for ICU-related respiratory infections (ENIRRIs) project http://ow.ly/sud930fU1e7