Tommaso Fossali

Prone position delays the progression of ventilator-induced lung injury in rats : Does lung strain distribution play a role?

Objective:To investigate if prone position delays the progression of experimental ventilator-induced lung injury, possibly due to a more homogeneous distribution of strain within lung parenchyma. Design:Prospective, randomized, controlled trial. Setting:Animal laboratory of a university hospital. Subjects:Thirty-five Sprague Dawley male rats (weight 257 ± 45 g). Interventions:Mechanical ventilation in either supine or prone position and computed tomography scan analysis. Measurements:Animals were ventilated in supine (n = 15) or prone (n = 15) position until a similar ventilator-induced lung injury was reached. To do so, experiments were interrupted when respiratory system elastance was 150% of baseline. Ventilator-induced lung injury was assessed as lung wet-to-dry ratio and histology. Time to reach lung injury was considered as a main outcome measure. In five additional animals, computed tomography scans (GE Light Speed QX/I, thickness 1.25 mm, interval 0.6 mm, 100 MA, 100 Kv) were randomly taken at end-expiration and end-inspiration in both positions, and quantitative analysis was performed. Data are shown as mean ± sd. Measurements and Main Results:Similar ventilator-induced lung injury was reached (respiratory system elastance, wet-to-dry ratio, and histology). The time taken to achieve the target ventilator-induced lung injury was longer with prone position (73 ± 37 mins vs. 112 ± 42, supine vs. prone, p = .011). Computed tomography scan analysis performed before lung injury revealed that at end-expiration, the lung was wider in prone position (p = .004) and somewhat shorter (p = .09), despite similar lung volumes (p = .455). Lung density along the vertical axis increased significantly only in supine position (p = .002). Lung strain was greater in supine as opposed to prone position (width strain, 7.8 ± 1.8% vs. 5.6 ± 0.9, supine vs. prone, p = .029). Conclusions:Prone position delays the progression of ventilator-induced lung injury. Computed tomography scan analysis suggests that a more homogeneous distribution of strain may be implicated in the protective role of prone position against ventilator-induced lung injury.

Lactate as a marker of energy failure in critically ill patients: hypothesis

Lactate measurement in the critically ill has been traditionally used to stratify patients with poor outcome. However, plasma lactate levels are the result of a finely tuned interplay of factors that affect the balance between its production and its clearance. When the oxygen supply does not match its consumption, organisms such as man who are forced to produce ATP for their integrity adapt in many different ways up to the point when energy failure occurs. Lactate, being part of the adaptive response, may then be used to assess the severity of the supply/demand imbalance. In such a scenario, the time to intervention becomes relevant: early and effective treatment may allow the cell to revert to a normal state, as long as the oxygen machinery (i.e. mithocondria) is intact. Conversely, once the mithocondria are deranged, energy failure occurs even in the presence of normoxia. The lactate increase in critically ill patients may therefore be viewed as an early marker of a potentially reversible state.

Pulse photoplethysmographic amplitude and heart rate variability during laparoscopic cholecystectomy: A prospective observational study

BACKGROUND Surgical stress affects the autonomic nervous system by increasing sympathetic outflow. One method of monitoring sympathetic activity is pulse photoplethysmographic analysis. From this two indices can be derived – autonomic nervous system state (ANSS) and ANSS index (ANSSi). It has recently been claimed that these indices can be used to measure sympathetic activity in anaesthetised patients, but their validity has not yet been demonstrated. OBJECTIVE To measure changes in pulse photoplethysmographic indices and determine any agreement with autonomic nervous system modulation of the cardiovascular system in healthy study participants during surgery under general anaesthesia. DESIGN Prospective observational study. SETTING Single-centre study based at a tertiary care centre in Milan, Italy. PATIENTS Healthy patients undergoing general anaesthesia for elective laparoscopic cholecystectomy. INTERVENTIONS ANSS, ANSSi, and heart rate variability (HRV) were analysed at three main times: baseline, after induction of general anaesthesia, and after pneumoperitoneum insufflation. MAIN OUTCOME MEASURES The magnitude of changes in photoplethysmographic and HRV indices was measured. The agreement between pulse photoplethysmographic and HRV-derived indices was assessed by Bland–Altman plots. RESULTS In total, 52 patients were enrolled and their data analysed. Both pulse photoplethysmographic and HRV indices changed during the study phases. An agreement was found between ANSSi and low frequency spectral components of HRV [bias 10.2nu, 95% confidence interval (CI) −13 to 33.4], high frequency spectral components of HRV (bias 6.1 nu, 95% CI −16.3 to 28.6), and low frequency/high frequency ratio (bias 16.1nu, 95% CI −1.4 to 33.5). The agreement was weaker between ANSSI and HRV indices. CONCLUSION The study endorses the use of pulse photoplethysmographic indices ANSS and ANSSi as surrogates to estimate changes of autonomic modulation of the cardiovascular system in healthy adults during surgery under general anaesthesia. Orcid ID: orcid.org/0000–0002–9616–803X.

Pulse Photoplethysmographic Analysis Estimates the Sympathetic Activity Directed to Heart and Vessels.

Background:Novel pulse photoplethysmographic–derived indices have been proposed as tools to measure autonomic nervous system (ANS) modulation in anesthetized and awake patients, but nowadays their experimental validation is lacking. The authors aimed to investigate the ability of pulse photoplethysmographic amplitude (PPGA), ANS state (ANSS), and ANSS index (ANSSi) to measure changes of ANS modulation in response to sympathetic stimulation. Methods:Ten awake healthy volunteers underwent two passive head-up tilts at 45° and 90°. The heart rate variability (HRV) and systolic arterial pressure variability were analyzed in the frequency domain as a measure of ANS modulation directed to the heart and the vessels. HRV, baroreflex sensitivity, and pulse photoplethysmographic indices were measured at baseline and after tilt maneuvers. The agreement between HRV-derived indices and pulse photoplethysmographic indices was assessed using Bland–Altman plots. Results:PPGA, ANSS, and ANSSi changed significantly during the study protocol. Head-up tilt decreased PPGA and ANSS and increased ANNSi. There was a good agreement between ANSSi and baroreflex sensitivity explored in the high-frequency band (bias, 0.23; 95% CI, −22.7 to 23.2 normalized units) and between ANSSi and the sympathovagal modulation directed to the heart (bias, 0.96; 95% CI, −8.7 to 10.8 normalized units). Conclusions:In controlled experimental conditions, novel pulse plethysmographic indices seem to estimate the changes of the sympathetic outflow directed to the vessels and the sympathovagal balance modulating heart rate. These indices might be useful in the future to monitor the fluctuation of sympathetic activity in anesthetized patients.

Association between autonomic control indexes and mortality in subjects admitted to intensive care unit

This study checks whether autonomic markers derived from spontaneous fluctuations of heart period (HP) and systolic arterial pressure (SAP) and from their interactions with spontaneous or mechanical respiration (R) are associated with mortality in patients admitted to intensive care unit (ICU). Three-hundred consecutive HP, SAP and R values were recorded during the first day in ICU in 123 patients. Population was divided into survivors (SURVs, n = 83) and non-survivors (NonSURVs, n = 40) according to the outcome. SURVs and NonSURVs were aged- and gender-matched. All subjects underwent modified head-up tilt (MHUT) by tilting the bed back rest segment to 60°. Autonomic control indexes were computed using time-domain, spectral, cross-spectral, complexity, symbolic and causality techniques via univariate, bivariate and conditional approaches. SAP indexes derived from time-domain, model-free complexity and symbolic approaches were associated with the endpoint, while none of HP variability markers was. The association was more powerful during MHUT. Linear cross-spectral and causality indexes were useless to separate SURVs from NonSURVs, while nonlinear bivariate symbolic markers were successful. When indexes were combined with clinical scores, only SAP variance provided complementary information. Cardiovascular control variability indexes, especially when derived after an autonomic challenge such as MHUT, can improve mortality risk stratification in ICU.

Mechanical ventilatory modes and cardioventilatory phase synchronization in acute respiratory failure patients

Cardioventilatory phase synchronization was studied in ten critically ill patients admitted in intensive care unit (ICU) for acute respiratory failure under two mechanical ventilatory modes: (i) pressure controlled ventilation (PCV); (ii) pressure support ventilation (PSV). The two modalities were administered to the same patient in different times in a random order. Cardioventilatory phase interactions were typified by plotting the relative position of a heartbeat, detected from the electrocardiogram and collected in n groups, within m ventilatory cycles as a function of the progressive cardiac beat number via the synchrogram. n:m phase synchronized patterns were detected by computing the variability of each phase group. The percent duration of the recording featuring phase synchronization was assessed as a measure of the strength of phase synchrony and tested against situations of full phase desynchronization between cardiac and ventilatory rhythms. Indexes quantifying the variability of the cardiac and ventilatory activities were computed as well. Findings proved that: (i) a significant presence of n:m phase synchronized patterns was detected in PCV; (ii) the strength of n:m phase synchronization was stronger during PCV than PSV; (iii) different strengths of cardioventilatory phase synchronization detected during PCV and PSV were found in presence of similar heart and ventilatory rates and alike variability. We conclude that mechanical ventilation can induce a significant presence of cardioventilatory phase synchronized patterns and this amount depends on the mode of mechanical ventilation. Future studies should test the eventual link of the level of phase coordination between heart and mechanical ventilation to a clinical outcome to understand whether featuring a certain degree of cardioventilatory phase synchronization is beneficial for the critical patient in ICU.

The Role of Failing Autonomic Nervous System on Life-Threatening Idiopathic Systemic Capillary Leak Syndrome

Idiopathic systemic capillary leak syndrome (ISCLS) is a rare disease that involves the endothelium and microcirculation, leading to an abrupt shift of fluids and proteins from the intravascular to the interstitial compartment. The consequence of the capillary leakage is a life-threatening hypovolemic shock that can lead to lethal multiple organ dysfunction. The autonomic nervous system (ANS) is central in regulating the cardiovascular response to hypovolemia, but ANS modulation in ISCLS has not yet been investigated. Here, we report ANS activity during acute phase and recovery from a severe ISCLS shock and speculate on the possibility that autonomic mechanisms underlie the pathogenesis of attacks.

Effects of laparoscopic radical prostatectomy on intraoperative autonomic nervous system control of hemodynamics

BACKGROUND Laparoscopic radical prostatectomy induces hemodynamic changes that have been supposed due to autonomic nervous system activity. The aim of this study is to measure the sympathetic and vagal modulation on hemodynamic response to steep Trendelenburg and pneumoperitoneum for laparoscopic surgery. METHODS Autonomic nervous system modulation was assessed noninvasively through heart rate variability and arterial pressure variability analysis in patients undergoing elective laparoscopic radical prostatectomy and in awake volunteers during head-down tilt. RESULTS Forty patients and 14 awake volunteers were studied. The induction of general anesthesia significantly decreased the heart rate, arterial pressure, vagal modulation, and sympathetic modulation. Steep Trendelenburg increased vagal and sympathetic modulation both in anesthetized and awake subjects. Pneumoperitoneum increased arterial pressure without effect on autonomic nervous system control in anesthetized patients. CONCLUSIONS Hemodynamic changes occurring during laparoscopic radical prostatectomy reveal autonomic response to the challenges (i.e. general anesthesia and head down position), and non-neurally mediated increase of arterial pressure caused by pneumoperitoneum. This study supports the notion that during laparoscopic radical prostatectomy the association between the vagal stimulation due to Trendelenburg positioning and sympathetic withdrawal caused by general anesthesia could lead to severe bradycardia and cardiac arrest in risky patients.