Gennaro Martucci

Double carbapenem as a rescue strategy for the treatment of severe carbapenemase-producing Klebsiella pneumoniae infections: a two-center, matched case–control study

BackgroundRecent reports have suggested the efficacy of a double carbapenem (DC) combination, including ertapenem, for the treatment of carbapenem-resistant Klebsiella pneumoniae (CR-Kp) infections. We aimed to evaluate the clinical impact of such a regimen in critically ill patients.MethodsThis case–control (1:2), observational, two-center study involved critically ill adults with a microbiologically documented CR-Kp invasive infection treated with the DC regimen matched with those receiving a standard treatment (ST) (i.e., colistin, tigecycline, or gentamicin).ResultsThe primary end point was 28-day mortality. Secondary outcomes were clinical cure, microbiological eradication, duration of mechanical ventilation and of vasopressors, and 90-day mortality. Forty-eight patients treated with DC were matched with 96 controls. Occurrence of septic shock at infection and high procalcitonin levels were significantly more frequent in patients receiving DC treatment (p < 0.01). The 28-day mortality was significantly higher in patients receiving ST compared with the DC group (47.9% vs 29.2%, p = 0.04). Similarly, clinical cure and microbiological eradication were significantly higher when DC was used in patients infected with CR-Kp strains resistant to colistin (13/20 (65%) vs 10/32 (31.3%), p = 0.03 and 11/19 (57.9%) vs 7/27 (25.9%), p = 0.04, respectively). In the logistic regression and multivariate Cox-regression models, the DC regimen was associated with a reduction in 28-day mortality (OR 0.33, 95% CI 0.13–0.87 and OR 0.43, 95% CI 0.23–0.79, respectively).ConclusionsImproved 28-day mortality was associated with the DC regimen compared with ST for severe CR-Kp infections. A randomized trial is needed to confirm these observational results.Trial registrationClinicalTrials.gov NCT03094494. Registered 28 March 2017.

Veno-venous ECMO in ARDS after post-traumatic pneumonectomy

Dear Editor, Post-traumatic pneumonectomy is rare, but burdened by high mortality (50–80 %) and high morbidity, with a complication rate of [85 %, most commonly pneumonia and respiratory failure [1]. Life-threatening acute respiratory distress syndrome (ARDS) can develop, and the worst outcome is associated with right pneumonectomy [2]. Extracorporeal membrane oxygenation (ECMO) is a rescue option in ARDS that allows for protective mechanical ventilation and potentially less ventilator-induced damage [3]. In the past, trauma cases requiring anticoagulation for ECMO implantation posed a clinical dilemma that has now been partially overcome with the advent of latest generation devices. We report a case of multifactorial ARDS (pneumonia, polytransfusion, and fluid overload) after right pneumonectomy due to blunt chest trauma in which the patient was non-responsive to protective ventilation and conventional therapy [4]. The patient survived with early implantation and 29 days of ECMO support. A 25-year-old male (170 cm, 61 kg) was admitted to another facility with major blunt thoracic trauma causing right hemothorax, right main bronchial disruption, left pneumothorax, and pneumomediastinum. Surgical treatment consisted of right pneumonectomy, left chest drainage, and tracheostomy. Despite lung-protective ventilation, the patient developed ARDS, with hypoxic–hypercapnic respiratory failure [partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2) 40 at 36 h]. A PaO2/ FiO2 ratio of\100 with a FiO2 of 1.0 for more than 6 h indicates that a patient has a [80 % risk of death (Extracorporeal Life Support Organization guidelines) (Fig. 1). The referring center requested a consultation, and despite the recent trauma and surgery, we decided to start the patient on veno-venous ECMO (VV-ECMO) which achieved stabilization and allowed the patient to be safely transported about 200 km by helicopter to our institute. Vessel cannulation [18 Fr return (jugular) and 24 Fr drainage (femoral)] was performed after the administration of a heparin bolus (80 IU/kg). VVECMO support (miniaturized tip-totip heparin-coated circuit; Cardiohelp System; Maquet, Rastatt, Germany) was initiated, with the initial goal of achieving a blood flow of about 4 l/ min (3,000 rpm and 2 l/min of sweep gas flow) in order to provide maximal oxygenation support, but avoid iatrogenic alkalosis. Protective mechanical ventilation for transport was a FiO2 of 40 %, peak inspiratory pressure (PIP) of 20 cm H2O, positive end-expiratory pressure (PEEP) of 10 cm H2O, and respiratory rate (RR) of 10 breaths/min (Oxylog 3000 Plus; Draeger, Menlo Park, CA). On arrival at our institute, after a few hours of ECMO, gas exchange parameters were adequate (pH 7.34, PaO2 116 mmHg, PaCO2 58 mmHg). Microbiological screening revealed colonization by Acinetobacter baumannii (multi-drug resistant), which was confirmed by the swab test and bronchoalveolar lavage. Continuous heparin infusion was initiated to maintain an activated partial thromboplastin time of 40–50 s, and an

Dysfunction of mechanical mitral prosthesis at 33rd week of pregnancy: ECMO support as a complex strategy for the mother and the fetus

Pregnant women with mechanical prosthetic heart valves have an increased risk of thrombosis and valve malfunctioning. Surgery carries a high risk of mortality for the mother and the fetus. A strategy for effective anticoagulation is crucial for these patients because both oral anticoagulants and heparin are associated with high risks for the mother and the fetus. The treatment of a pregnant woman with thrombosis and valve malfunction is a challenge, even for multidisciplinary teams, as cardiac surgery carries considerable risks. We present a woman at her 33rd week of pregnancy affected by congestive cardiac decompensation due to mechanical mitral prosthesis dysfunction. Given the expanded indication for ECMO and the recent evidence of the procedure’s increased safety, even in the peri-partum period, we centered the treatment on VA-ECMO initiation before a Cesarean section (C-section) to guarantee support during surgery and avoid excessive anticoagulation or hypoperfusion to the fetus and as a bridge to cardiac surgery two days later. The strategy resulted in a good outcome with no complications for the mother and the fetus and a reasonable length of stay

Intracranial hemorrhage during extracorporeal membrane oxygenation: does family history play a role?

Extracorporeal membrane oxygenation (ECMO) is a lifesaving mechanical support for reversible severe heart or respiratory injury [1]. ECMO circuit causes a wide inflammatory response and coagulation disequilibrium due to the exposure of blood to a non-biological surface. Procoagulant state, consumption of clotting factors, impaired platelet function, thrombocytopenia, and fibrinolysis coexist. Therefore, systemic anticoagulation is required to prevent life-threatening thrombosis and excessive bleeding [2]. Over the past decade, the use of ECMO in adults has increased [3, 4]. Substantial technological improvements have made the circuit systems simpler and safer, causing less bleeding than in the past. ECMO can be associated with different neurological complications, such as seizures, ischemic or hemorrhagic stroke, and acute disseminated encephalomyelitis in H1N1affected patients. ECMO registries have reported a rate of intracranial hemorrhage of 4–15 %. In the majority the outcome is catastrophic [5–7]. Predictive scores proposed to achieve the best cost-effectiveness and individual patient’s prognosis do not involve neurological outcomes [8]. Because of the increasing indication for ECMO, the occurrence of neurological injuries will be likely an emergent phenomenon that should be understood better and monitored. Possibly, neurologists should be involved in the initial stages of the decision-making process and evaluation of prognosis and outcome. In the first 6 months of 2014, we managed 16 cases of ECMO for different causes of severe ARDS unresponsive to conventional treatment (7 H1N1 infection, 5 pneumonia of various origins, 3 end-stage respiratory failure as bridge to lung transplantation, and 1 primary graft failure PGF), with an overall survival of 65 %. Among these patients, we had two cases of intracranial hemorrhage, which caused death of both patients. We present them because of the fortuitous finding of a family history of vascular cerebral episodes: a bleeding cerebral vascular anomaly in one case and hemorrhagic stroke in the other one.

Understanding adrenal crisis

Incidence and mortality Approximately 5–17 cases of adrenal crisis (AC) occur per 100 patient years in patients with primary or secondary adrenal insufficiency (AI) [1, 2]. The mortality rate is estimated to be between 0.5% and 2%. Norwegian data indicate that overall, 1 in 7 patients with Addison’s disease eventually dies from AC. It is estimated that AC will account for 5500–10,600 excess deaths in the European Union in the next decade [3]. Often, these are preventable deaths in relatively young patients in the emergency department (ED) or intensive care unit (ICU) occurring from cardiorespiratory arrest in hypovolemic shock after delayed or insufficient steroid replacement, contributing to the excess mortality in patients at risk. Adequate treatment of AC using stress-dose intravenous steroids is often delayed, even when AI is known and patients present their emergency card to EDs or retrieval services (European Steroid Emergency Card www.endocrinology.org/adrenal-crisis) [4].

Anticoagulation and Transfusions Management in Veno-Venous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: Assessment of Factors Associated With Transfusion Requirements and Mortality

Purpose: We describe an approach for anticoagulation and transfusions in veno-venous–extracorporeal membrane oxygenation (VV-ECMO), evaluating factors associated with higher transfusion requirements, and their impact on mortality. Methods: Observational study on consecutive adults supported with VV-ECMO for acute respiratory distress syndrome (ARDS). We targeted an activated partial thromboplastin time of 40 to 50 seconds and a hematocrit of 24% to 30%. Univariate and multiple analyses were done to evaluate factors associated with transfusion requirements and the influence of increasing transfusions on mortality during ECMO. Results: In a cohort of 82 VV-ECMO patients (PRedicting dEath for SEvere ARDS on VV-ECMO [PRESERVE] score: 4, Interquartile range [IQR]: 3-5, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction [RESP] score: 2, IQR: 2-4), 76 (92.7%) patients received at least 1 unit of packed red blood cells (PRBCs) during the intensive care unit stay related to ECMO (median PRBC/d 156 mL, IQR: 93-218; median ECMO duration 14 days, IQR: 8-22). A higher requirement of PRBC transfusions was associated with pre-ECMO hematocrit, and with the following conditions during ECMO: platelet nadir, antithrombin III (ATIII), and stage 3 of acute kidney injury (all P < .05). Sixty-two (75.6%) patients survived ECMO. Pre-ECMO hospital stay, PRBC transfusion, and septic shock were associated with mortality (all P < .05). The adjusted odds ratio for each 100mL/d increase in PRBC transfusion was 1.9 (95% confidence interval [CI]: 1.1-3.2, P = .01); for the development of septic shock it was 15.4 (95% CI: 1.7-136.8, P = .01), and for each day of pre-ECMO stay it was 1.1 (95% CI: 1-1.2, P = .04). Conclusion: Implementation of a comprehensive protocol for anticoagulation and transfusions in VV-ECMO for ARDS resulted in a low PRBC requirement, and an ECMO survival comparable to data in the literature. Lower ATIII emerged as a factor associated with increased need for transfusions. Higher PRBC transfusions were associated with ECMO mortality. Further investigations are needed to better understand the right level of anticoagulation in ECMO, and the factors to take into account in order to manage personalized transfusion practice in this select setting.

Challenge of Pregnancy in Patients With Pre-Capillary Pulmonary Hypertension: Veno-Arterial Extracorporeal Membrane Oxygenation as an Innovative Support for Delivery

article Challenge of Pregnancy in Patients With Pre-Capillary Pulmonary Hypertension: Veno-Arterial Extracorporeal Membrane Oxygenation as an Innovative Support for Delivery Patrizio Vitulo, MD, Marta Beretta, MD, Gennaro Martucci, MD, Cesar Mario Hernandez Baravoglia, MD, Giuseppe Romano, MD, Alessandro Bertani, MD, Lavinia Martino, MD, Adriana Callari, MD, Giovanna Panarello, MD, Michele Pilato, MD, Antonio Arcadipane, MD

Access to Intensive Care Medicine for Undocumented Migrants: The Destiny of an ECMO Center in the Middle of the Mediterranean Basin

Dear Editor, A huge migratory pressure has been exerted on southern European countries over the last few years. Considering its implications for public health, and an expected duration of years to come, migration has been included by the European Commission among the ten top political priorities, and was a recent topic of discussion in Intensive Care Medicine [1, 2]. After entry into European Union (EU) countries, migrants can have several health risks due to a long and difficult journey, social instability, poverty, and lack of food and water. Intensive care may be required for several reasons, such as infectious disease, trauma, rhabdomyolysis, acute kidney and/or liver injury, and heat stroke or hypothermia; but also for pre-existing diseases impossible to treat in low-resource health systems [3]. ISMETT, because of its location in Sicily (Italy), often the first Italian destination for migrant boats crossing the Mediterranean, has seen an increase in hospital admissions of migrants. In 2015, 22 were admitted to our 78-bed institute for specialized therapies, 7 (32 %) of whom to the ICU, for a total of 232 days of ICU stay. We also had two challenging ECMO cases closely correlated with the migrant status of the patients, who had access to life support because of the presence of a specialized center en route to their new lives. Case 1: a 22-year-old man from Mali placed on venovenous extracorporeal membrane oxygenation (VVECMO) after 2 days of mechanical ventilation due to chemical pneumonia developed after a long journey in a migrant boat hold from Libya. The acute respiratory distress syndrome (ARDS) picture was severe (P/F ratio 62, despite inhaled nitric oxide; PEEP 14; and diffuse pulmonary opacities, PRESERVE score 3, RESP score 1) [4]. The patient recovered after 8 days of ECMO and was discharged to the inpatient unit after a total ICU stay of 17 days, prolonged by PTSD.

Air Transport: Fixed-Wing and Helicopter

Without mobile support, it might be impossible to transport patients needing extracorporeal membrane oxygenation (ECMO). Aeromedical transport is used to transfer critically ill patients over large distances or in areas with inadequate road networks and geographical and infrastructural barriers. This form of aerial transport grew out of basic military models into highly sophisticated and integrated civilian systems of care. The principal advantage of air transport is the shorter journey and the ability to operate from a range of surfaces. Moreover, helipads are more diffuse than airports.

Impact of cannula design on packed red blood cell transfusions: technical advancement to improve outcomes in extracorporeal membrane oxygenation

Background Technological improvement has contributed to making veno-venous extracorporeal membrane oxygenation (VV-ECMO) safer and easier, spreading its use in acute respiratory failure (ARF). Methods This is a retrospective observational study carried out in the ECMO center at IRCCS-ISMETT, a medical center focused on end-stage organ failure treatment in Italy. We investigated the effect of different cannula designs on the amount of blood product transfused. Eighty-nine consecutive patients affected with ARF on VV-ECMO from 2008 to 2016 were compared according to type of cannulation: older percutaneous cannula (Standard group, 52 patients) and HLS© BIOLINE-coated, but with shorter drainage cannula (BIOLINE group, 37 patients). Results The two study groups were comparable in terms of baseline characteristics [age, body mass index (BMI), Simplified Acute Physiology Score (SAPS-II), Sequential Organ Failure Assessment (SOFA), Predicting Death For Severe ARDS on VV-ECMO (PRESERVE) score] and ECMO management [median hematocrit (Htc), platelet nadir, antithrombin III (AT III), heparin, activated partial thromboplastin time (APTT)]. In the BIOLINE group, a lower amount of packed red blood cells (pRBC) was transfused considering both total number [4 units, interquartile range (IQR) 1-9 vs. 12 units, IQR 5.5-21; P<0.01] and mL of pRBC/day of ECMO support (91, IQR 21-158 vs. 193.5, IQR 140.5-254; P<0.01). In the BIOLINE group, a trend in reduction of ECMO days (P=0.05) and length of intensive care unit (ICU) stay was found (P=0.06), but no differences in rates of ECMO weaning and ICU discharge were evidenced. The BIOLINE group constituted a saving of €1,295.20 per patient/treatment, counting the costs for cannulation and pRBC administration. Conclusions More biocompatible and shorter drainage cannula may represent one of the contributing factors to a reduction in transfusions and costs of VV-ECMO in the current ongoing technological improvement in ECMO.