[Blood gas analysis in the intensive cardiac care unit]. / La rapida lettura dell'emogasanalisi in unità di terapia intensiva cardiologica.

Arterial blood gas (ABG) analysis is a simple and quick test that can provide multiple respiratory and metabolic parameters. The interpretation of ABG analysis and acid-base disorders represents one of the most complex chapters of clinical medicine. In this brief review, the authors propose a rational approach that sequentially analyzes the information offered by the ABG to allow a rapid classification of the respiratory, metabolic or mixed disorder. The patient's history and clinical-instrumental assessment are the framework in which to insert the information derived from the ABG analysis in order to characterize the critical heart patient.

Biopharmaceutical Assessment of Mesh Aerosolised Plasminogen, a Step towards ARDS Treatment.

Acute respiratory distress syndrome (ARDS) is a severe complication of lung injuries, commonly associated with bacterial, fungal and viral infections, including SARS-CoV-2 viral infections. ARDS is strongly correlated with patient mortality and its clinical management is very complex, with no effective treatment presently available. ARDS involves severe respiratory failure, fibrin deposition in both airways and lung parenchyma, with the development of an obstructing hyaline membrane drastically limiting gas exchange. Moreover, hypercoagulation is related to deep lung inflammation, and a pharmacological action toward both aspects is expected to be beneficial. Plasminogen (PLG) is a main component of the fibrinolytic system playing key roles in various inflammation regulatory processes. The inhalation of PLG has been proposed in the form of the off-label administration of an eyedrop solution, namely, a plasminogen-based orphan medicinal product (PLG-OMP), by means of jet nebulisation. Being a protein, PLG is susceptible to partial inactivation under jet nebulisation. The aim of the present work is to demonstrate the efficacy of the mesh nebulisation of PLG-OMP in an in vitro simulation of clinical off-label administration, considering both the enzymatic and immunomodulating activities of PLG. Biopharmaceutical aspects are also investigated to corroborate the feasibility of PLG-OMP administration by inhalation. The nebulisation of the solution was performed using an Aerogen® SoloTM vibrating-mesh nebuliser. Aerosolised PLG showed an optimal in vitro deposition profile, with 90% of the active ingredient impacting the lower portions of a glass impinger. The nebulised PLG remained in its monomeric form, with no alteration of glycoform composition and 94% of enzymatic activity maintenance. Activity loss was observed only when PLG-OMP nebulisation was performed under simulated clinical oxygen administration. In vitro investigations evidenced good penetration of aerosolised PLG through artificial airway mucus, as well as poor permeation across an Air-Liquid Interface model of pulmonary epithelium. The results suggest a good safety profile of inhalable PLG, excluding high systemic absorption but with good mucus diffusion. Most importantly, the aerosolised PLG was capable of reversing the effects of an LPS-activated macrophage RAW 264.7 cell line, demonstrating the immunomodulating activity of PLG in an already induced inflammatory state. All physical, biochemical and biopharmaceutical assessments of mesh aerosolised PLG-OMP provided evidence for its potential off-label administration as a treatment for ARDS patients.

Life-threatening paradoxical thromboembolism in a patient with patent foramen ovale.

BACKGROUND: Venous thromboembolism represents the third most frequent acute cardiovascular syndrome worldwide. Its clinical manifestations are deep vein thrombosis and/or pulmonary embolism. Despite a considerable mortality, diagnosis is often missed.  CASE PRESENTATION: We report the management of a female patient with high-risk pulmonary thromboembolism treated initially with thromboaspiration, complicated by embolus jailing in a patent foramen ovale. In this situation, left cardiac chambers and systemic circulation were jeopardized by this floating embolus. CONCLUSIONS: High-risk pulmonary embolism requires reperfusion strategy but sometimes mechanical thromboaspiration may be not fully successful; transesophageal echocardiography led to a prompt diagnosis of this unexpected finding; in this very particular case, open surgery represented a bail-out procedure to avoid cerebral and systemic embolism.

Ultrasound emergency lateral-to-medial parasternal pericardiocentesis with high frequency probe in COVID-19: a case report.

Background: The pathological involvement of the heart is frequent in SARS-Coronavirus-2 infection (COVID-19) with various clinical and echocardiographic manifestations during the course of the disease. Case summary: A 69-year-old female patient with severe COVID-19-related acute respiratory distress syndrome undergoing mechanical ventilation developed acute left ventricular dysfunction, that successfully improved with vasoactive therapy. After 5 days, she suddenly developed hemodynamic instability due to acute onset of pericardial effusion, which required emergency pericardiocentesis. Ultrasound-guided parasternal pericardiocentesis with high-frequency linear probe and lateral-to-medial in-plane approach was performed by inserting a central venous catheter using a Seldinger technique. 700 mL of serous fluid was drained resolving the acute critical state. Discussion: Pericardial effusion with cardiac tamponade is a rare manifestation of Covid-19. Despite the diffusion of echocardiography, emergency cardiac procedures could be particularly difficult to be performed in a pandemic scenario of limited resources and the heterogeneous skills of the professional figures involved in the management of COVID-19 patients. The spread of expertise in ultrasound-guided vascular cannulation makes this approach attractive for anesthesiologists, emergency medicine and critical care specialists too. Furthermore in this pericardiocentesis' technique, the high-frequency linear probe adds optimal spatial resolution to maintain a close control of the needle's direction. However the need of a good parasternal view and a deep ultrasound knowledge are crucial to avoid iatrogenic complications. In conclusion, ultrasound-guided lateral-to-medial parasternal pericardiocentesis with high-frequency linear probe is an alternative to treat potential lethal acute haemodynamic instability due to cardiac tamponade.

The Potential Role of Aerosolized Phosphodiesterase 3 Inhibitor Enoximone in the Management of Coronavirus Disease 2019 Hypoxemia: A Case Report.

Despite the various parenchymal presentation of coronavirus disease 2019 (COVID-19) pneumonia, the involvement of the vascular component, the reduction of perfusion in noninjured part of the lung and secondary right to left shunt play an important role in the genesis of the respiratory insufficiency. We present the case of a 72-year-old woman admitted to Livorno Hospital for severe respiratory insufficiency due to SARS-CoV-2 infection unresponsive to noninvasive in whom administration of nebulized phosphodiesterase 3 (PDE3) inhibitor enoximone was able to improve oxygenation avoiding tracheal intubation. Intravenous infusions of phosphodiesterase inhibitors are commonly used as pulmonary vasodilators in the management of pulmonary hypertension. This is the first case showing that inhaled route administration of PDE3 inhibitor enoximone could be important in the management of COVID-19 hypoxemia, to restore perfusion in noninjured part of the lung, improving oxygenation and avoiding risks of systemic infusion.

Repurposing of Plasminogen: An Orphan Medicinal Product Suitable for SARS-CoV-2 Inhalable Therapeutics.

The SARS-CoV-2 infection is associated with pulmonary coagulopathy, which determines the deposition of fibrin in the air spaces and lung parenchyma. The resulting lung lesions compromise patient pulmonary function and increase mortality, or end in permanent lung damage for those who have recovered from the COVID-19 disease. Therefore, local pulmonary fibrinolysis can be efficacious in degrading pre-existing fibrin clots and reducing the conversion of lung lesions into lasting scars. Plasminogen is considered a key player in fibrinolysis processes, and in view of a bench-to-bedside translation, we focused on the aerosolization of an orphan medicinal product (OMP) for ligneous conjunctivitis: human plasminogen (PLG-OMP) eye drops. As such, the sterile and preservative-free solution guarantees the pharmaceutical quality of GMP production and meets the Ph. Eur. requirements of liquid preparations for nebulization. PLG-OMP aerosolization was evaluated both from technological and stability viewpoints, after being submitted to either jet or ultrasonic nebulization. Jet nebulization resulted in a more efficient delivery of an aerosol suitable for pulmonary deposition. The biochemical investigation highlighted substantial protein integrity maintenance with the percentage of native plasminogen band > 90%, in accordance with the quality specifications of PLG-OMP. In a coherent way, the specific activity of plasminogen is maintained within the range 4.8-5.6 IU/mg (PLG-OMP pre-nebulization: 5.0 IU/mg). This is the first study that focuses on the technological and biochemical aspects of aerosolized plasminogen, which could affect both treatment efficacy and clinical dosage delivery. Increasing evidence for the need of local fibrinolytic therapy could merge with the availability of PLG-OMP as an easy handling solution, readily aerosolizable for a fast translation into an extended clinical efficacy assessment in COVID-19 patients.

Transesophageal echocardiography during MitraClip® procedure.

The percutaneous mitral valve (MV) repair procedure performed with the MitraClip delivery system is increasingly used to treat severe mitral regurgitation in high-risk patients. The treatment involves percutaneous insertion and positioning of a clip between the MV leaflets. Transesophageal echocardiography (TEE) plays a key role in the procedure by providing information regarding clip navigation, clip alignment to the MV coaptation line, transmitral advancement of the system, leaflet grasping, confirmation of valve tissue catching, and assessment of the final result. Real-time 3-dimensional TEE has increasing value in percutaneous MV repair providing high-quality visualization of both the heart and the intravascular devices. Optimal visualization by 3-dimensional TEE is obtained through both the atrial and ventricular aspects. In contrast to MV surgery, where TEE is involved in the prebypass assessment phase and in evaluation of the final repair, TEE is mandatory to guide management during MitraClip repair. Cardiac anesthesiologists may provide assistance to interventional cardiologists during the procedure itself in addition to their anesthetic-related tasks.

Ventriculoarterial decoupling in human septic shock.

INTRODUCTION: Septic shock is the most severe manifestation of sepsis. It is characterized as a hypotensive cardiovascular state associated with multiorgan dysfunction and metabolic disturbances. Management of septic shock is targeted at preserving adequate organ perfusion pressure without precipitating pulmonary edema or massive volume overload. Cardiac dysfunction often occurs in septic shock patients and can significantly affect outcomes. One physiologic approach to detect the interaction between the heart and the circulation when both are affected is to examine ventriculoarterial coupling, which is defined by the ratio of arterial elastance (Ea) to left ventricular end-systolic elastance (Ees). In this study, we analyzed ventriculoarterial coupling in a cohort of patients admitted to ICUs who presented with vs without septic shock. METHODS: In this retrospective cross-sectional opportunity study, we measured routine hemodynamics using indwelling arterial and pulmonary arterial catheters and transthoracic echocardiograms in 25 septic patients (group S) and 25 non-septic shock patients (group C) upon ICU admission. Ees was measured by echocardiography using a single-beat (EesSB) method. Ea was calculated as 0.9 systolic arterial pressure/stroke volume, and then the Ea/EesSB ratio was calculated (normal value <1.36). RESULTS: In group S, 21 patients had an Ea/EesSB ratio >1.36 (uncoupled). The four patients with Ea/EesSB ratios ≤1.36 had higher EesSB values than patients with Ea/EesSB ratios >1.36 (P = 0.007), although Ea measurements were similar in both groups (P = 0.4). In group C, five patients had uncoupled Ea/EesSB ratios. No correlation was found between EesSB and left ventricular ejection fraction and between Ea/EesSB ratio and mixed venous oxygen saturation in septic shock patients. CONCLUSIONS: Upon admission to the ICU, patients in septic shock often display significant ventriculoarterial decoupling that is associated with impaired left ventricular performance. Because Ea/Ees decoupling alters cardiovascular efficiency and cardiac energetic requirements independently of Ea or Ees, we speculate that septic patients with ventriculoarterial uncoupling may benefit from therapy aimed at normalizing the Ea/Ees ratio.

Non invasive evaluation of cardiomechanics in patients undergoing MitrClip procedure.

BACKGROUND: In the last recent years a new percutaneous procedure, the MitraClip, has been validated for the treatment of mitral regurgitation. MitraClip procedure is a promising alternative for patients unsuitable for surgery as it reduces the risk of death related to surgery ensuring a similar result. Few data are present in literature about the variation of hemodynamic parameters and ventricular coupling after Mitraclip implantation. METHODS: Hemodynamic data of 18 patients enrolled for MitraClip procedure were retrospectively reviewed and analyzed. Echocardiographic measurements were obtained the day before the procedure (T0) and 21 ± 3 days after the procedure (T1), including evaluation of Ejection Fraction, mitral valve regurgitation severity and mechanism, forward Stroke Volume, left atrial volume, estimated systolic pulmonary pressure, non invasive echocardiographic estimation of single beat ventricular elastance (Es(sb)), arterial elastance (Ea) measured as systolic pressure • 0.9/ Stroke Volume, ventricular arterial coupling (Ea/Es(sb) ratio). Data were expressed as median and interquartile range. Measures obtained before and after the procedure were compared using Wilcoxon non parametric test for paired samples. RESULTS: Mitraclip procedure was effective in reducing regurgitation. We observed an amelioration of echocardiographic parameters with a reduction of estimated systolic pulmonary pressure (45 to 37,5 p = 0,0002) and left atrial volume (110 to 93 p = 0,0001). Despite a few cases decreasing in ejection fraction (37 to 35 p = 0,035), the maintained ventricular arterial coupling after the procedure (P = 0,67) was associated with an increasing in forward stroke volume (60,3 to 78 p = 0,05). CONCLUSION: MitraClip is effective in reducing mitral valve regurgitation and determines an amelioration of hemodynamic parameters with preservation of ventricular arterial coupling.

Role of thrombolestagrophy in monitoring perioperative coagulation status and effect of thromboprophylaxis in bariatric surgery.

BACKGROUND: Thromboelastography is a technique that surveys the properties of viscoelastic blood clot. The purpose of this paper was to evaluate the hypercoagulability state and the effect of antithrombotic prophylaxis on thromboelastogram (TEG) results in bariatric surgery. METHODS: Twenty-five patients enrolled received 0.8 ml of nodraparin starting on the day before surgery and continuing postoperatively. TEG profile was collected before induction of anesthesia, on the first and third postoperative days. Each sample was run also in a cup added with heparinase to eliminate the interference of antithrombotic prophylaxis. RESULTS: TEG analysis with heparinase showed a tendency to reduce the r-time (rate of initial fibrin formation) and k-time (time to clot firmness) and increase the alpha angle (rate of clot growth), while an increase of maximal amplitude (MA, a measure of maximal stiffness of the clot; p = 0.01) and GI or shear elastic modules strength (p = 0.03)was observed from basal to postoperative day 3 (POD3). TEG without heparinase evidenced and increase of r-time (p = 0.02) and k-time (p = 0.05), a reduction of the alpha angle (p = 0.03), and an increase of MA (p = 0.01) and GI (p = 0.03) from basal to POD3. The comparison of TEG techniques showed that normal TEGs had lower values of r-time and k-time and higher values of alpha angles and MA than TEG with heparinase. No differences were evident for basal and POD1 samples and the G values comparing the two TEG technique. No correlation was observed between the variation of normal TEG parameters and dosage of anticoagulant used in each patient. CONCLUSIONS: Our patients presented a tendency to hypercoagulability determined most by MA and GI. Comparison between TEGs indicates that low-molecular-weight heparin not titrated on weight is able to determine a reduction of hypercoabulable tendency in the early postoperative period with few effects on increasing MA and GI.