Use of point-of-care ultrasound (POCUS) to monitor neonatal and pediatric extracorporeal life support.

Extracorporeal membrane oxygenation (ECMO) is an invasive life support technique that requires a blood pump, an artificial membrane lung, and vascular cannulae to drain de-oxygenated blood, remove carbon dioxide, oxygenate, and return it to the patient. ECMO is generally used to provide advanced and prolonged cardiopulmonary support in patients with refractory acute cardiac and/or respiratory failure. After its first use in 1975 to manage a severe form of meconium aspiration syndrome with resultant pulmonary hypertension, the following years were dominated by the use of ECMO to manage neonatal respiratory failure and limited to a few centers across the world. In the 1990s, evidence for neonatal respiratory ECMO support increased; however, the number of cases began to decline with the use of newer pharmacologic therapies (e.g., inhaled nitric oxide, exogenous surfactant, and high-frequency oscillatory ventilation). On the contrary, pediatric ECMO sustained steady growth. Combined advances in ECMO technology and bedside medical management have improved general outcomes, although ECMO-related complications remain challenging. Point-of-care ultrasound (POCUS) is an essential tool to monitor all phases of neonatal and pediatric ECMO: evaluation of ECMO candidacy, ultrasound-guided ECMO cannulation, daily evaluation of heart and lung function and brain perfusion, detection and management of major complications, and weaning from ECMO support.  Conclusion: Based on these considerations and on the lack of specific guidelines for the use of POCUS in the neonatal and pediatric ECMO setting, the aim of this paper is to provide a systematic overview for the application of POCUS during ECMO support in these populations. What is Known: • Extracorporeal membrane oxygenation (ECMO) provides advanced cardiopulmonary support for patients with refractory acute cardiac and/or respiratory failure and requires appropriate monitoring. • Point-of-care ultrasound (POCUS) is an accessible and adaptable tool to assess neonatal and pediatric cardiac and/or respiratory failure at bedside. What is New: • In this review, we discussed the use of POCUS to monitor and manage at bedside neonatal and pediatric patients supported with ECMO. • We explored the potential use of POCUS during all phases of ECMO support: pre-ECMO assessment, ECMO candidacy evaluation, daily evaluation of heart, lung and brain function, detection and troubleshooting of major complications, and weaning from ECMO support.

Renal Outcomes of Dialysis-Dependent Acute Kidney Injury in Noncritically Ill Patients: A Retrospective Study.

INTRODUCTION: Acute kidney injury (AKI) is a common complication among hospitalized patients, potentially affecting short- and long-term clinical outcomes. In this retrospective study, we evaluated renal outcomes in noncritically ill patients who required acute hemodialysis (HD) because of an AKI episode occurring during hospitalization. METHODS: Sixty-three hemodynamically stable patients with AKI undergoing acute intermittent HD were included. Kidney function was evaluated at baseline control (pre-AKI), at AKI diagnosis and during the follow-up. According to serum creatinine and the estimated glomerular filtration rate (eGFR), we defined three clinical conditions: renal recovery, different stages of acute kidney disease (AKD), and chronic kidney disease (CKD). RESULTS: Among the 63 patients evaluated, 34 patients (54%) had a history of CKD. Six patients (10%) presented early full renal recovery. HD treatment was stopped in 38 patients (60%), while 25 patients (40%) required maintenance HD. Dialysis-independent patients presented lower comorbidity and higher baseline eGFR and delta creatinine, compared to dialysis-dependent patients. Baseline CKD, previous AKI episodes, and parenchymal causes of AKI were associated with a significant risk of dialysis dependence. At 1-month control, 15 patients (39%) presented AKD stage 0, 6 patients (16%) AKD stage 1, and 17 patients (44%) AKD stage 2-3. At 3-month control, 29 out of 38 patients recovering from AKI (76%) presented CKD. AKD stage was significantly correlated with the risk of CKD development, which, resulted higher in patients with lower baseline eGFR. CONCLUSIONS: AKI might represent a risk factor for the development of chronic kidney damage, even in noncritically ill patients.

Effect of Levosimendan Treatment in Pediatric Patients With Cardiac Dysfunction: An Update of a Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Levosimendan increasingly has been used to treat heart failure and cardiac dysfunction in pediatric patients. Currently, there is only limited evidence that this drug positively affects outcomes. The authors' aim was to investigate the effects of levosimendan on hemodynamic parameters and outcomes in pediatric patients in all clinical settings. The study design was a systematic review of randomized and nonrandomized studies. Randomized clinical trials (RCTs) were included in a meta-analysis. The primary outcome of the meta-analysis was the effect of levosimendan on central venous oxygen saturation (ScvO2) and lactate values as surrogate markers of low-cardiac-output syndrome. The study setting was any acute care setting. Study participants were pediatric patients (age <18 years) receiving levosimendan, and the intervention was levosimendan versus any control treatment. The authors identified 44 studies published from 2004 to 2020, including a total of 1,131 pediatric patients. Nine studies (enrolling 547 patients) were RCTs, all performed in a pediatric cardiac surgery setting. Three RCTs were judged to carry a low risk of bias. In the RCTs, levosimendan administration was associated with a significant improvement of ScvO2 (p = 0.03) and a trend toward lower postoperative lactate levels (p = 0.08). No differences could be found for secondary outcomes. Levosimendan use in pediatric patients is not associated with major side effects and may lead to hemodynamic improvement after cardiac surgery. However, its impact on major clinical outcomes remains to be determined. Overall, the quality of evidence for levosimendan use in pediatric patients is low, and further high-quality RCTs are needed.

In vivo calibration of esophageal pressure in the mechanically ventilated patient makes measurements reliable.

BACKGROUND: Esophageal pressure (Pes) can provide information to guide mechanical ventilation in acute respiratory failure. However, both relative changes and absolute values of Pes can be affected by inappropriate filling of the esophageal balloon and by the elastance of the esophagus wall. We evaluated the feasibility and effectiveness of a calibration procedure consisting in optimization of balloon filling and subtraction of the pressure generated by the esophagus wall (Pew). METHODS: An esophageal balloon was progressively filled in 36 patients under controlled mechanical ventilation. VBEST was the filling volume associated with the largest tidal increase of Pes. Esophageal wall elastance was quantified and Pew was computed at each filling volume. Different filling strategies were compared by performing a validation occlusion test. RESULTS: Fifty series of measurements were performed. VBEST was 3.5 ± 1.9 ml (range 0.5-6.0). Esophagus elastance was 1.1 ± 0.5 cmH2O/ml (0.3-3.1). Both Pew and the result of the occlusion test differed among filling strategies. At filling volumes of 0.5, VBEST and 4.0 ml respectively, Pew was 0.0 ± 0.1, 2.0 ± 1.9, and 3.0 ± 1.7 cmH2O (p < 0.0001), whereas the occlusion test was satisfactory in 22%, 98%, and 88% of cases (p < 0.0001). CONCLUSIONS: Under mechanical ventilation, an increase of balloon filling above the conventionally recommended low volumes warrants complete transmission of Pes swings, but is associated with significant elevation of baseline. A simple calibration procedure allows finding the filling volume associated with the best transmission of tidal Pes change and subtracting the associated baseline artifact, thus making measurement of absolute values of Pes reliable.

Multiple electrolyte disorders in a neurosurgical patient: solving the rebus.

BACKGROUND: It is important to ensure an adequate sodium and volume balance in neurosurgical patients in order to avoid the worsening of brain injury.Indeed, hyponatremia and polyuria, that are frequent in this patient population, are potentially harmful, especially if not promptly recognized.Differential diagnosis is often challenging, including disorders, which, in view of similar clinical pictures, present very different pathophysiological bases, such as syndrome of inappropriate antidiuresis, cerebral/renal salt wasting syndrome and diabetes insipidus. CASE PRESENTATION: Here we present the clinical report of a 67-year-old man with a recent episode of acute subarachnoid haemorrhage, admitted to our ward because of severe hyponatremia, hypokalemia and huge polyuria.We performed a complete workup to identify the underlying causes of these alterations and found a complex picture of salt wasting syndrome associated to primary polydipsia. The appropriate diagnosis allowed us to correct the patient hydro-electrolyte balance. CONCLUSION: The comprehension of the pathophysiological mechanisms is essential to adequately recognize and treat hydro-electrolyte disorders, also solving the most complex clinical problems.

Extracorporeal Carbon Dioxide Removal: From Pathophysiology to Clinical Applications; Focus on Combined Continuous Renal Replacement Therapy.

Lung-protective ventilation (LPV) with low tidal volumes can significantly increase the survival of patients with acute respiratory distress syndrome (ARDS) by limiting ventilator-induced lung injuries. However, one of the main concerns regarding the use of LPV is the risk of developing hypercapnia and respiratory acidosis, which may limit the clinical application of this strategy. This is the reason why different extracorporeal CO2 removal (ECCO2R) techniques and devices have been developed. They include low-flow or high-flow systems that may be performed with dedicated platforms or, alternatively, combined with continuous renal replacement therapy (CRRT). ECCO2R has demonstrated effectiveness in controlling PaCO2 levels, thus allowing LPV in patients with ARDS from different causes, including those affected by Coronavirus disease 2019 (COVID-19). Similarly, the suitability and safety of combined ECCO2R and CRRT (ECCO2R-CRRT), which provides CO2 removal and kidney support simultaneously, have been reported in both retrospective and prospective studies. However, due to the complexity of ARDS patients and the limitations of current evidence, the actual impact of ECCO2R on patient outcome still remains to be defined. In this review, we discuss the main principles of ECCO2R and its clinical application in ARDS patients, in particular looking at clinical experiences of combined ECCO2R-CRRT treatments.

Combined extracorporeal CO2 removal and renal replacement therapy in a pregnant patient with COVID-19: a case report.

Background. Pregnant women are at high risk of Coronavirus disease 2019 (COVID-19) complications, including acute respiratory distress syndrome. Currently, one of the cornerstones in the treatment of this condition is lung-protective ventilation (LPV) with low tidal volumes. However, the occurrence of hypercapnia may limit this ventilatory strategy. So, different extracorporeal CO2 removal (ECCO2R) procedures have been developed. ECCO2R comprises a variety of techniques, including low-flow and high-flow systems, that may be performed with dedicated devices or combined with continuous renal replacement therapy (CRRT). Case description. Here, we report a unique case of a pregnant patient affected by COVID-19 who required extracorporeal support for multiorgan failure. While on LPV, because of the concomitant hypercapnia and acute kidney injury, the patient was treated with an ECCO2R membrane inserted in series after a hemofilter in a CRRT platform. This combined treatment reducing hypercapnia allowed LPV maintenance at the same time while providing kidney replacement and ensuring maternal and fetal hemodynamic stability. Adverse effects consisted of minor bleeding episodes due to the anticoagulation required to maintain the extracorporeal circuit patency. The patient's pulmonary and kidney function progressively recovered, permitting the withdrawal of any extracorporeal treatment. At the 25th gestational week, the patient underwent spontaneous premature vaginal delivery because of placental abruption. She gave birth to an 800-gram female baby, who three days later died because of multiorgan failure related to extreme prematurity. Conclusions. This case supports using ECCO2R-CRRT combined treatment as a suitable approach in the management of complex conditions, such as pregnancy, even in the case of severe COVID-19.

Mechanisms underlying sCD40 production in hemodialysis patients.

CD40 and its ligand (CD40L) regulate several cellular functions, including T and B-cell activation. The soluble form of CD40 (sCD40) antagonizes CD40/CD40L interaction. Patients undergoing hemodialysis (HD) present elevated sCD40 serum levels, which underlying molecular mechanisms are unknown. We studied sCD40 serum and urinary levels, CD40 membrane and gene expression and membrane shedding in HD, uremic not-HD patients (UR) and healthy subjects (N). We found that in HD sCD40 serum levels were higher than UR and N, being significantly elevated in anuric patients, and that sCD40 correlated to renal function in UR subjects, who presented also a reduced sCD40 urinary excretion rate. HD and UR presented reduced CD40 membrane and gene expression. The concentration of TNF-α converting enzyme (TACE), responsible for CD40 cleavage was not different between HD and N. Therefore the reduced renal clearance is the main cause of elevated sCD40 levels in HD. This finding could have relevant clinical implications.

Successful Extracorporeal Blood Purification Therapy using Double Haemoadsorption Device in Severe Endotoxin Septic Shock: A Case Report.

Introduction: In patients admitted to the Intensive Care Unit (ICU), sepsis can lead to acute kidney injury (AKI), which may require the initiation of continuous renal replacement therapy (CRRT) in 15-20% of cases. There is no consensus about the best extracorporeal treatment to choose in septic patients with AKI. Case presentation: We describe the case of a 70-year-old woman admitted to the ICU with a severe endotoxin septic shock due to Neisseria meningitidis serogroup C. Despite prompt medical intervention, including fluid resuscitation, high dose vasopressor, inotrope support, and broad-spectrum antimicrobial treatment, in a few hours patient's haemodynamic worsened and she developed multi-organ failure, including severe AKI, requiring CRRT. So, continuous veno-venous haemodiafiltration was started, using an oXiris® haemodiafilter set, in series with an adsorber device (CytoSorb®). After 48 hours of this combined extracorporeal treatment, haemodynamic parameters improved, allowing a significant reduction of the vasoactive therapy, with a concomitant decrease in endotoxin and inflammatory markers serum levels. In the following days patient's conditions still improved and renal function recovered. Conclusions: Timely extracorporeal blood purification therapy, using a double haemoadsorption device, may be effective in the management of severe septic shock.

The syndrome of inappropriate antidiuresis: pathophysiology, clinical management and new therapeutic options.

Hyponatremia is a marker of different underlying diseases and it can be a cause of morbidity itself; this implies the importance of a correct approach to the problem. The syndrome of inappropriate antidiuresis (SIAD) is one of the most common causes of hyponatremia: it is a disorder of sodium and water balance characterized by urinary dilution impairment and hypotonic hyponatremia, in the absence of renal disease or any identifiable non-osmotic stimulus able to induce antidiuretic hormone (ADH) release; according to its definition, it is diagnosed through an exclusion algorithm. SIAD is usually observed in hospitalized patients and its prevalence may be as high as 35%. The understanding of the syndrome has notably evolved over the last years, as reflected by the significant change in the name, once the syndrome of inappropriate secretion of ADH (SIADH), today SIAD. This review is up to date and it analyses the newest notions about pathophysiological mechanisms, classification, management and therapy of SIAD, including vaptans.

Hyperkalemia-induced acute flaccid paralysis: a case report.

Acute flaccid paralysis is a medical emergency that may be caused by primary neuro-muscular disorders, metabolic alterations, and iatrogenic effects. Severe hyperkalemia is also a potential cause, especially in elderly patients with impaired renal function. Early diagnosis is essential for appropriate management. Here, we report the case of a 78-year-old woman with hypertension and diabetes presenting to the emergency department because of pronounced asthenia, rapidly evolving in quadriparesis. Laboratory examinations showed severe hyperkalemia of 9.9 mmol/L, metabolic acidosis, kidney failure (creatinine 1.6 mg/dl), and hyperglycemia (501 mg/dl). The electrocardiography showed absent P-wave, widening QRS, and tall T-waves. The patient was immediately treated with medical therapy and a hemodialysis session, presenting a rapid resolution of electrocardiographic and neurological abnormalities. This case offers the opportunity to discuss the pathogenesis, the clinical presentation, and the management of hyperkalemia-induced acute flaccid paralysis.

Neutrophil gelatinase-associated lipocalin does not predict acute kidney injury in heart failure.

BACKGROUND: Acute cardiorenal syndrome type 1 (CRS-1) is defined by a rapid cardiac dysfunction leading to acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalin (NGAL) is expressed on the surface of human neutrophils and epithelial cells, such as renal tubule cells, and its serum (sNGAL) and urinary have been used to predict AKI in different clinical settings. AIM: To characterize CRS-1 in a cohort of patients with acute heart diseases, evaluating the potentiality of sNGAL as an early marker of CRS-1. METHODS: We performed a retrospective cohort, multi-centre study. From January 2010 to December 2011, we recruited 202 adult patients admitted to the coronary intensive care unit (CICU) with a diagnosis of acute heart failure or acute coronary syndrome. We monitored the renal function to evaluate CRS-1 development and measured sNGAL levels within 24 h and after 72 h of CICU admission. RESULTS: Overall, enrolled patients were hemodynamically stable with a mean arterial pressure of 92 (82-107) mmHg, 55/202 (27.2%) of the patients developed CRS-1, but none of them required dialysis. Neither the NGAL delta value (AUC 0.40, 95%CI: 0.25-0.55) nor the NGAL peak (AUC 0.45, 95%CI: 0.36-0.54) or NGAL cut-off (≥ 140 ng/mL) values were statistically significant between the two groups (CRS-1 vs no-CRS1 patients). The area under the ROC curve for the prediction of CRS-1 was 0.40 (95%CI: 0.25-0.55) for the delta NGAL value and 0.45 (95%CI: 0.36-0.54) for the NGAL peak value. Finally, in multivariate analysis, the risk of developing CRS-1 was correlated with age > 60 years, urea nitrogen at admission and 24 h-urine output (AUC 0.83, SE = 60.5% SP = 93%), while sNGAL was not significantly correlated. CONCLUSION: In our population, sNGAL does not predict CRS-1, probably as a consequence of the mild renal injury and the low severity of heart disease. So, these data might suggest that patient selection should be taken into account when considering the utility of NGAL measurement as a biomarker of kidney damage.

[Spontaneous rupture of a simple renal cyst: clinical management]. / Rottura spontanea di cisti renale semplice: gestione clinica.

Spontaneous renal bleeding mainly occurs in patients with polycystic kidney diseases or cancer. Indeed, despite the high prevalence of simple cysts, their spontaneous atraumatic rupture is a rare event. Underlying mechanisms may involve the increase of intracystic pressure and/or the development of a haemorrhage into the cyst. Management of this condition includes surgery, interventional radiology or conservative strategies. Here, we report a case of spontaneous rupture of a simple renal cyst, successfully managed with conservative treatment.

Renal involvement in mushroom poisoning: The case of Orellanus syndrome.

Although mushroom poisoning is a rare cause of acute renal injury, in some cases it may lead to the development of a severe and irreversible renal failure. Orellanus syndrome is the most important example of organic renal damage related to mushroom consumption. It is caused by the ingestion of orellanine, the main toxin of different types of Cortinarius mushrooms (Cortinarius speciosissimus, C. orellanus, C. orellanoides, etc.), and it is characterized by progressive clinical phases with a predominant kidney involvement, finally requiring renal replacement therapy in about 10% of cases. Renal damage is often late and associated with a histological picture of interstitial nephritis. Diagnosis is essentially clinical and no specific therapy has been shown to be effective in preventing and treating renal damage. Here, we describe the case of a patient with mixed wild mushroom poisoning, presenting the typical clinical signs and course of the Orellanus syndrome. This case offers us the opportunity to review the main clinical features of this severe and little-known intoxication.