To Be Frail or Not to Be Frail: This Is the Question-A Critical Narrative Review of Frailty.

Many factors have contributed to rendering frailty an emerging, relevant, and very popular concept. First, many pandemics that have affected humanity in history, including COVID-19, most recently, have had more severe effects on frail people compared to non-frail ones. Second, the increase in human life expectancy observed in many developed countries, including Italy has led to a rise in the percentage of the older population that is more likely to be frail, which is why frailty is much a more common concern among geriatricians compared to other the various health-care professionals. Third, the stratification of people according to the occurrence and the degree of frailty allows healthcare decision makers to adequately plan for the allocation of available human professional and economic resources. Since frailty is considered to be fully preventable, there are relevant consequences in terms of potential benefits both in terms of the clinical outcome and healthcare costs. Frailty is becoming a popular, pervasive, and almost omnipresent concept in many different contexts, including clinical medicine, physical health, lifestyle behavior, mental health, health policy, and socio-economic planning sciences. The emergence of the new "science of frailty" has been recently acknowledged. However, there is still debate on the exact definition of frailty, the pathogenic mechanisms involved, the most appropriate method to assess frailty, and consequently, who should be considered frail. This narrative review aims to analyze frailty from many different aspects and points of view, with a special focus on the proposed pathogenic mechanisms, the various factors that have been considered in the assessment of frailty, and the emerging role of biomarkers in the early recognition of frailty, particularly on the role of mitochondria. According to the extensive literature on this topic, it is clear that frailty is a very complex syndrome, involving many different domains and affecting multiple physiological systems. Therefore, its management should be directed towards a comprehensive and multifaceted holistic approach and a personalized intervention strategy to slow down its progression or even to completely reverse the course of this condition.

Intraoperative cardiac function assessment by transesophageal echocardiography versus FloTrac/Vigileo™ system during pectus excavatum surgical repair.

BACKGROUND: Pectus excavatum (PE), a congenital deformity of the chest wall, can lead to cardiac compression and related symptoms. PE surgical repair can improve cardiac function. Intraoperative transesophageal echocardiography (TEE) has been successfully employed to assess intraoperative hemodynamic variations in patients undergoing PE repair. FloTrac/Vigileo™ system (Edwards Life-sciences Irvine, CA) (FT/V) is a minimally invasive cardiac output monitoring system. This retrospective study aimed to assess hemodynamic changes in surgical repair of PE using FT/V and concordance with parameters measured by TEE. RESULTS: N=19 patients submitted to PE repair via Ravitch or Nuss technique were enrolled. Intraoperative cardiac assessments simultaneously obtained via TEE and FT/V system were investigated. The agreement between TEE-derived cardiac output (CO-TEE) and FT/V system parameter (COAP) was evaluated. The relationship between COTEE and COAP was analyzed for all data using linear regression analysis. A significant correlation between COAP and COTEE values (R = 0.65, p < 0.001) was found. Bland-Altman analysis of COAP and COTEE showed a bias of 0.13 L/min and a limit of agreement of - 2.33 to 2.58 L/min, with a percentage error of 48%. Intraoperative measurements by TEE and FT/V both showed a significant increase in CO after surgical correction of PE (p < 0.005). CONCLUSIONS: FT/V system compared to TEE in hemodynamic monitoring during PE surgery yielded clinically unacceptable results due to a high percentage error. After surgical correction of PE, CO, measured by TEE and FT/V, significantly improved.

Propofol sedation reduces diaphragm activity in spontaneously breathing patients: ultrasound assessment.

BACKGROUND: The diaphragm is the most important respiratory muscle in humans, and the close relationship between inspired volume and diaphragmatic movement in normal subjects has led to investigations into diaphragmatic activity using ultrasound, during spontaneous breathing and sedative drug infusion. METHODS: A total of 36 consecutive patients undergoing diagnostic procedures under deep propofol sedation were studied. Ultrasound measurements included the following: diaphragmatic thickening end-inspiration (TEI) and end-expiration (TEE). Diaphragmatic thickening fraction (DTF) was calculated from [(TEI - TEE) / TEE] at various time points (at T0 basal; at T1 during propofol infusion; at T2 awakening). Oxygen was administered at 4 L/min, and oxygen saturation (SpO2), end tidal CO2 (EtCO2) and respiratory rate (RR) were recorded. RESULTS: TEI, and TEE decreased by 26.7% and 17.4%, respectively, during propofol infusion (T0 versus T1) (P<0.001), and rapidly recovered at T2 (22.7% and 15.8%). At procedure end (T0 versus T2), TEI maintained a significant reduction (10%, P<0.001), whereas TEE recovered completely. DTF decreased by 56.7% at T1 (P<0.001) but increased by 76.9% (P=0.001) at T2. Recovery after awakening (T0 versus T2) did not reach the baseline value, with a 23.4% difference (P<0.001). SpO2 remained above 96% and EtCO2 below 43 mmHg with no desaturation episodes observed. CONCLUSIONS: Our study showed that deep propofol sedation affects muscle activity in healthy patients. While diaphragmatic strength decreased during sedation, there was no clinically relevant effect on SpO2. The study also confirmed that ultrasound is suitable for measuring diaphragm activity during a normal clinical procedure.

Bedside Assessment of the Microvascular Venous Compartment in Cardiac Surgery Patients With Valvular Diseases Undergoing Cardiopulmonary Bypass.

OBJECTIVE: Blood volume reserve for venous return and the effects of cardiopulmonary bypass (CPB) on microvascular bed partitioning and blood flow were examined in patients with valvular diseases. DESIGN: Prospective, consecutive, case-control study. SETTING: Single university hospital. PARTICIPANTS: The study comprised 20 adult cardiac surgery patients and 20 healthy volunteers. INTERVENTIONS: Cardiovascular and microvascular variables were collected soon after the induction of anesthesia, after commencement of CPB, 20 minutes after separation from CPB, and in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: The unstressed and stressed volumes (Vu, Vs) and pressures therein (Pit, Ps) were measured in the brachioradial muscle with near-infrared spectroscopy, applying incremental venous occlusions. At the first time point, Vs and Pit showed lower and higher values, respectively, than those of control patients, but Vs increased with Vu during the study, whereas Pit remained unchanged. Fluid balance correlated with Pit (r = 0.83, p<0.001) and hemoglobin (r = 0.78, p = 0.004). A nonlinear regression was found between fluid balance and ΔVu (r = 0.90, p<0.001) [y = 1.85+37.43(-0.01×x)]. The Vu/Pit and Vs/Ps ratios were lower than those of the control patients. Blood flow correlated to Vs/Ps (r = 0.75, p<0.001). The time constant was lower than reference (p = 0.005) and increased 10 times after CPB. CONCLUSIONS: Cardiac surgery patients have a limited blood volume reserve for venous return due to a reduced microvascular bed capacitance. This study demonstrated that during CPB a positive fluid balance induced an extravascular pressure increase and further reduced blood volume reserve.

RIFLE-based data collection/management system applied to a prospective cohort multicenter Italian study on the epidemiology of acute kidney injury in the intensive care unit.

The epidemiology of acute kidney injury (AKI) has been difficult to explore in the past, due to different definitions across various studies. Nevertheless, this is a very important topic today in light of the high morbidity and mortality of critically ill patients presenting renal dysfunction during their stay in the intensive care unit (ICU). The case mix has changed over the years, and AKI is a common problem in critically ill patients often requiring renal replacement therapy (RRT). The RIFLE and AKIN initiatives have provided a unifying definition for AKI, making possible large retrospective studies in different countries. The present study aims at validating a unified web-based data collection and data management tool based on the most recent AKI definition/classification system. The interactive database is designed to elucidate the epidemiology of AKI in a critically ill population. As a test, we performed a prospective observational multicenter study designed to prospectively evaluate all incident admissions in ten ICUs in Italy and the relevant epidemiology of AKI. Thus, a simple user-friendly web-based data collection tool was created with the scope to serve for this study and to facilitate future multicenter collaborative efforts. We enrolled 601 consecutive incident patients into the study; 25 patients with end-stage renal disease were excluded, leaving 576 patients for analysis. The median age was 66 (IQR 53-76) years, 59.4% were male, while median Simplified Acute Physiology Score II and Acute Physiology and Chronic Health Evaluation II scores were 43 (IQR 35-54) and 18 (IQR 13-24), respectively. The most common diagnostic categories for ICU admission were: respiratory (27.4%), followed by neurologic (17%), trauma (14.4%), and cardiovascular (12.1%). Crude ICU and hospital mortality were 21.7% and median ICU length of stay was 5 (IQR 3-14) days. Of 576 patients, 246 patients (42.7%) had AKI within 24 h of ICU admission, while 133 developed new AKI later during their ICU stay. RIFLE-initial class was Risk in 205 patients (54.1%), Injury in 99 (26.1%) and Failure in 75 (19.8%). Progression of AKI to a worse RIFLE class was seen in 114 patients (30.8% of AKI patients). AKI patients were older, with higher frequency of common risk factors. 116 AKI patients (30.6%) fulfilled criteria for sepsis during their ICU stay, compared to 33 (16.7%) of non-AKI patients (p < 0.001). 48 patients (8.3%) were treated with RRT in the ICU. Patients were started on RRT a median of 2 (IQR 0-6) days after ICU admission. AKI patients were started on RRT a median of 1 (IQR 0-4) day after fulfilling criteria for AKI. Median duration of RRT was 5 (IQR 2-10) days. AKI patients had a higher crude ICU mortality (28.8 vs. 8.1%, non-AKI; p < 0.001) and longer ICU length of stay (median 7 vs. 3 days, non-AKI; p < 0.001). Crude ICU mortality and ICU length of stay increased with greater severity of AKI. 225 (59.4% of AKI patients) had complete recovery of renal function, with a serum creatinine at time of ICU discharge which was ≤120% of baseline; an additional 51 AKI patients (13.5%) had partial renal recovery, while 103 (27.2%) had not recovered renal function at the time of death or ICU discharge. The study supports the use of RIFLE as an optimal classification system to stage AKI severity. AKI is indeed a deadly complication for ICU patients, where the level of severity is correlated with mortality and length of stay. The tool developed for data collection was user-friendly and easy to implement. Some of its features, including a RIFLE class alert system, may help the treating physician to systematically collect AKI data in the ICU and possibly may guide specific decisions on the institution of RRT.

A comparative evaluation of thermodilution and partial CO2 rebreathing techniques for cardiac output assessment in critically ill patients during assisted ventilation.

OBJECTIVE: To evaluate the reliability and clinical value of partial noninvasive CO2 (NICO2) rebreathing technique for measuring cardiac output compared with standard thermodilution in a group of intensive care nonpostoperative patients. DESIGN AND SETTING: Clinical investigation in a university hospital ICU. PATIENTS: Twelve mechanically ventilated patients with high (n=6) and low (n=6) pulmonary shunt fractions. MEASUREMENTS AND RESULTS: Thirty-six paired measurements of cardiac output were carried out with NICO2 and thermodilution in patients ventilated in pressure-support mode and sedated with a sufentanil continuous infusion to obtain a Ramsay score value of 2. The mean cardiac output was: thermodilution 7.27+/-2.42 l/min; NICO2 6.10+/-1.66 l/min; r2 was 0.62 and bias -1.2 l/min+/-1.5. Mean values of cardiac output were similar in the low shunt group (Qs/Qt < 20), with r2=0.90 and a bias of 0.01 l/min+/-0.4; conversely, in the high pulmonary shunt group (Qs/Q > 35%) the mean was 9.32+/-1.23 l/min with thermodilution and a mean NICO2CO value was 6.97+/-1.53 l/min, with r2 of 0.38 and a bias of -2.3 l+/-1.2 min. CONCLUSIONS: The partial CO2 rebreathing technique is reliable in measuring cardiac output in nonpostoperative critically ill patients affected by diseases causing low levels of pulmonary shunt, but underestimates it in patients with shunt higher than 35%.