Mechanical chest compression and extracorporeal life support for out-of-hospital cardiac arrest. A 30-month observational study in the metropolitan area of Milan, Italy.

BACKGROUND: Return of spontaneous circulation (ROSC) is achieved in 25% of out-of-hospital cardiac arrest (OHCA) patients. Mechanical chest compression (mechCPR) may maintain better perfusion during transport, allowing hospital treatments like extracorporeal circulation life support (ECLS). We aim to assess the effectiveness of a pre-hospital protocol introduction. METHODS: Observational, retrospective study assessing all OHCA patients aged 12-75, with no-flow time <20 min in a metropolitan area (Milan, Italy, 2013-2016). PRIMARY OUTCOMES: ROSC and Cerebral Performance Category score (CPC) ≤2 at hospital discharge. Logistic regressions with multiple comparison adjustments balanced with propensity scores calculated with inverse probability of treatment weighting were performed. RESULTS: 1366 OHCA were analysed; 305 received mechCPR, 1061 manual chest compressions (manCPR), and 108 ECLS. ROSC and CPC ≤2 were associated with low-flow minutes (odds ratio [95% confidence interval] 0.90 [0.88-0.91] and 0.90 [0.87-0.93]), shockable rhythm (2.52 [1.71-3.72] and 10.68 [5.63-20.28]), defibrillations number (1.15 [1.07-1.23] and 1.15 [1.04-1.26]), and mechCPR (1.86 [1.17-2.96] and 2.06 [1.11-3.81]). With resuscitation times >13 min, mechCPR achieved more frequently ROSC compared to manCPR. Among ECLS patients, 70% had time exceeding protocol: 8 (7.5%) had CPC ≤2 (half of them with low-flow times between 45 and 90 min), 2 (1.9%) survived with severe neurological disabilities, and 13 brain-dead (12.0%) became organ donors. CONCLUSIONS: MechCPR patients achieved ROSC more frequently than manual CPR patients; mechCPR was a crucial factor in an ECLS protocol for refractory OHCA. ECLS offered a chance of survival to patients who would otherwise die.

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.

Impact of the FloTrac/VigileoTM Monitoring on Intraoperative Fluid Management and Outcome after Liver Resection.

BACKGROUNDS: Perioperative fluid-therapy is a still a debated issue. In hepatic surgery, volume load must be strictly monitored to assure both a safe hemodynamics and low central venous pressure (CVP) to limit the backflow bleeding. Retrospectively, we compared intraoperative fluid management before and after the adoption of a semi-invasive hemodynamic monitoring. METHODS: We compared patients submitted to liver resection monitored by FloTrac/VigileoTM (group A) vs. patients who did not (group B). We searched for differences about hemodynamics, fluid therapy and outcome. RESULTS: Three hundred fifty-five patients underwent hepatic resection due to neoplasm: group A - n = 179 and group B - n = 176. At the end of the resection, patients of group A showed a higher mean arterial pressure (MAP) than group B (74 ± 12 vs. 49.4 ± 8 mm Hg, respectively; p < 0.001). Cardiac index and stroke volume variation in group A were within a normal range. Fluid input was higher in group B than in group A (12.0 ± 3.4 vs. 7.6 ± 3.1 mL/kg/h, respectively; p < 0.001) and fluid balance was significantly different: group A -400 ± 1,527 vs. group B 326 ± 1,527 mL (p < 0.001). Group B showed a greater number of cases complicated outcomes (36 vs. 20; p = 0.014). Considering only those subjects who were able to reach their hemodynamic targets (MAP ≥65 mm Hg and CVP ≤7 mm Hg), we found similar data. CONCLUSIONS: Patients who received a monitored fluid therapy experienced a safer outcome.

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.

Serum lactate in liver resection with intermittent Pringle maneuver: the "square-root- shape.

BACKGROUND: Serum lactate (sLac) concentration during liver resection with intermittent hepatic hilum clamping (i.e. Pringle maneuver, PM) was retrospectively investigated. METHODS: A total of 133 patients who underwent liver resection were enrolled. We analyzed the sLac peri-operatively. Correlations were searched between the PM and lactatemia and its variations (i.e. lactate clearance, cLac) and other factors which it might be related to. Lactatemia in triplicate intraoperatively was recorded, just after the awakening, and 1 and 2 h later. The cLac between two consecutive measurements [(sLac1 - sLac2 )/sLac1 ] was computed. RESULTS: A reliable dependence of sLac was found from the cumulative PM. More than 76 min of cumulative Pringle Time (cPT) exposed patients to a worse cLac at the end of the resection phase (P < 0.0001). We found cPT >76 min, global operation time >365 min and bleeding >225 ml to be predictors of hyperlactatemia (sLac >4 mmol/L). Normal liver resulted as a risk factor for hyperlactatemia and steatosis was not (P = 0.030 vs. P = 0.325). Finally, cLac showed a "square-root- shape, just like the mathematical operation sign. CONCLUSIONS: Lactatemia during liver resection depends on the duration of PM, bleeding and the duration of the operation. Normal liver may expose the patient to the risk of hyperlactatemia.

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.

Severe Plasmodium falciparum malaria in the intensive care unit: A 6-year experience in Milano, Italy.

BACKGROUND: Severe imported Plasmodium falciparum malaria is a potentially life-threatening disease with a reported mortality rate of 5-10% when patients are admitted to the Intensive Care Unit. METHODS: To retrospectively review the clinical aspects, the value of severity predictive scores and the management of patients with severe P. falciparum malaria admitted to an ICU in Milano, Italy between January 2010 and December 2015. RESULTS: Twelve patients were included: seven were male and five female with a median age of 43 years. All were initially treated with intravenous quinine. Median parasitaemia upon admission was 14,5% (range 1-20%). At the time of ICU admission, 3 patients (25%) had 5 or more World Health Organization criteria for severe malaria while another 6 of them developed one or more of the latter during their stay in ICU. Five required mechanical ventilation because of respiratory failure due to ARDS. Four patients required renal replacement therapy. Three patients underwent blood exchange transfusion. All patients survived. CONCLUSIONS: Our retrospective evaluation of adults patients admitted to the ICU with severe imported P. falciparum malaria demonstrated a favourable outcome. Severity predictive scores currently in use probably overestimate the risk of malaria mortality in patients treated in health care systems of high income countries.

Quantifying Net Synergy/Redundancy of Spontaneous Variability Regulation via Predictability and Transfer Entropy Decomposition Frameworks.

Objective: Indexes assessing the balance between redundancy and synergy were hypothesized to be helpful in characterizing cardiovascular control from spontaneous beat-to-beat variations of heart period (HP), systolic arterial pressure (SAP), and respiration (R). Methods: Net redundancy/synergy indexes were derived according to predictability and transfer entropy decomposition strategies via a multivariate linear regression approach. Indexes were tested in two protocols inducing modifications of the cardiovascular regulation via baroreflex loading/unloading (i.e., head-down tilt at -25° and graded head-up tilt at 15°, 30°, 45°, 60°, 75°, and 90°, respectively). The net redundancy/synergy of SAP and R to HP and of HP and R to SAP were estimated over stationary sequences of 256 successive values. Results: We found that: 1) regardless of the target (i.e., HP or SAP) redundancy was prevalent over synergy and this prevalence was independent of type and magnitude of the baroreflex challenge; 2) the prevalence of redundancy disappeared when decoupling inputs from output via a surrogate approach; 3) net redundancy was under autonomic control given that it varied in proportion to the vagal withdrawal during graded head-up tilt; and 4) conclusions held regardless of the decomposition strategy. Conclusion: Net redundancy indexes can monitor changes of cardiovascular control from a perspective completely different from that provided by more traditional univariate and multivariate methods. Significance: Net redundancy measures might provide a practical tool to quantify the reservoir of effective cardiovascular regulatory mechanisms sharing causal influences over a target variable.Objective: Indexes assessing the balance between redundancy and synergy were hypothesized to be helpful in characterizing cardiovascular control from spontaneous beat-to-beat variations of heart period (HP), systolic arterial pressure (SAP), and respiration (R). Methods: Net redundancy/synergy indexes were derived according to predictability and transfer entropy decomposition strategies via a multivariate linear regression approach. Indexes were tested in two protocols inducing modifications of the cardiovascular regulation via baroreflex loading/unloading (i.e., head-down tilt at -25° and graded head-up tilt at 15°, 30°, 45°, 60°, 75°, and 90°, respectively). The net redundancy/synergy of SAP and R to HP and of HP and R to SAP were estimated over stationary sequences of 256 successive values. Results: We found that: 1) regardless of the target (i.e., HP or SAP) redundancy was prevalent over synergy and this prevalence was independent of type and magnitude of the baroreflex challenge; 2) the prevalence of redundancy disappeared when decoupling inputs from output via a surrogate approach; 3) net redundancy was under autonomic control given that it varied in proportion to the vagal withdrawal during graded head-up tilt; and 4) conclusions held regardless of the decomposition strategy. Conclusion: Net redundancy indexes can monitor changes of cardiovascular control from a perspective completely different from that provided by more traditional univariate and multivariate methods. Significance: Net redundancy measures might provide a practical tool to quantify the reservoir of effective cardiovascular regulatory mechanisms sharing causal influences over a target variable.

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.

Pharmacological Modulation of Ischemic-Reperfusion Injury during Pringle Maneuver in Hepatic Surgery. A Prospective Randomized Pilot Study.

BACKGROUND: The Pringle maneuver, which is performed during liver surgery to reduce blood loss, may result in liver ischemia/reperfusion injury resulting in metabolic, immunological, and microvascular changes, which may lead to hepatocellular damage. The aim of this study was the investigation of the effects of N-acetylcysteine (NAC) and methylprednisolone (MET) in the modulation of liver warm ischemia during hepatic resection. METHODS: Forty-eight patients were enrolled in a pilot double-blind, randomized clinical trial. The patients received either NAC, MET, or placebo. The primary endpoint was the reduction in postoperative alanine aminotransferase and bilirubin. The secondary endpoint was the difference in morbidity and mortality. RESULTS: All the 48 patients had liver resection with no mortality. Morbidity was observed in 8 (16 %) patients equally distributed among the groups. There was a significant favorable recovery of liver function tests in patients treated with NAC or MET compared with the placebo when the Pringle maneuver exceeded 70 min. CONCLUSIONS: The administration of NAC or MET prior to the Pringle maneuver during hepatic resection is associated with lower postoperative aberration in liver function tests compared with placebo when the Pringle maneuver exceeded 70 min. Larger studies are required to validate our findings and to investigate the specific role of NAC and MET in liver surgery.

Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach.

Septic shock remains a major problem in Intensive Care Unit, with high lethality and high-risk second lines treatments. In this preliminary retrospective investigation we examined plasma metabolome and clinical features in a subset of 20 patients with severe septic shock (SOFA score >8), enrolled in the multicenter Albumin Italian Outcome Sepsis study (ALBIOS, NCT00707122). Our purpose was to evaluate the changes of circulating metabolites in relation to mortality as a pilot study to be extended in a larger cohort. Patients were analyzed according to their 28-days and 90-days mortality. Metabolites were measured using a targeted mass spectrometry-based quantitative metabolomic approach that included acylcarnitines, aminoacids, biogenic amines, glycerophospholipids, sphingolipids, and sugars. Data-mining techniques were applied to evaluate the association of metabolites with mortality. Low unsaturated long-chain phosphatidylcholines and lysophosphatidylcholines species were associated with long-term survival (90-days) together with circulating kynurenine. Moreover, a decrease of these glycerophospholipids was associated to the event at 28-days and 90-days in combination with clinical variables such as cardiovascular SOFA score (28-day mortality model) or renal replacement therapy (90-day mortality model). Early changes in the plasma levels of both lipid species and kynurenine associated with mortality have potential implications for early intervention and discovering new target therapy.

Effect of variations of the complexity of the target variable on the assessment of Wiener-Granger causality in cardiovascular control studies.

We hypothesized that Wiener-Granger causality (WGC) indexes might have different abilities in coping with modifications of the complexity of the target variable in the context of the assessment of the cardiovascular control from spontaneous fluctuations of heart period (HP), systolic arterial pressure (SAP) and respiratory activity (R). After having defined the universe of knowledge as the set Ω = {HP, SAP, R} and the unpredictability decrement (UPD) as the difference between the prediction error variances of the target signal computed in Ω after excluding the presumed cause (i.e. the restricted Ω) and in Ω, we computed the following frequently utilized WGC indexes: (i) the plain UPD; (ii) the fractional UPD (FUPD) by dividing UPD by the prediction error variance in the restricted Ω; (iii) the normalized UPD (NUPD) by dividing UPD by the prediction error variance in Ω; (iv) the log-unpredictability decrement (LUPD) by applying the logarithm transformation to the prediction error variances before computing the UPD. The hypothesis was tested over two experimental protocols known to produce modifications of the complexity of HP variability: graded head-up tilt (HUT) inducing a gradual decrease of the HP complexity with tilt table inclination and head-down tilt (HDT) inducing the opposite trend. We demonstrated that: (1) when the strength of the causal relations from SAP to HP during HUT and from R to HP during HDT is assessed in Ω, WGC indexes reach different conclusions; (2) UPD is biased by modifications of the complexity of HP dynamics; (3) FUPD, NUPD and LUPD are less sensitive to changes of the complexity of the target dynamic, even though they have slightly different statistical power, being the NUPD the weakest one and FUPD and LUPD the strongest ones. We conclude that UPD should be avoided when assessing WGC and FUPD and LUPD should be privileged over NUPD.

Disentangling cardiovascular control mechanisms during head-down tilt via joint transfer entropy and self-entropy decompositions.

A full decomposition of the predictive entropy (PE) of the spontaneous variations of the heart period (HP) given systolic arterial pressure (SAP) and respiration (R) is proposed. The PE of HP is decomposed into the joint transfer entropy (JTE) from SAP and R to HP and self-entropy (SE) of HP. The SE is the sum of three terms quantifying the synergistic/redundant contributions of HP and SAP, when taken individually and jointly, to SE and one term conditioned on HP and SAP denoted as the conditional SE (CSE) of HP given SAP and R. The JTE from SAP and R to HP is the sum of two terms attributable to SAP or R plus an extra term describing the redundant/synergistic contribution to the JTE. All quantities were computed during cardiopulmonary loading induced by -25° head-down tilt (HDT) via a multivariate linear regression approach. We found that: (i) the PE of HP decreases during HDT; (ii) the decrease of PE is attributable to a lessening of SE of HP, while the JTE from SAP and R to HP remains constant; (iii) the SE of HP is dominant over the JTE from SAP and R to HP and the CSE of HP given SAP and R is prevailing over the SE of HP due to SAP and R both in supine position and during HDT; (iv) all terms of the decompositions of JTE from SAP and R to HP and SE of HP due to SAP and R were not affected by HDT; (v) the decrease of the SE of HP during HDT was attributed to the reduction of the CSE of HP given SAP and R; (vi) redundancy of SAP and R is prevailing over synergy in the information transferred into HP both in supine position and during HDT, while in the HP information storage synergy and redundancy are more balanced. The approach suggests that the larger complexity of the cardiac control during HDT is unrelated to the baroreflex control and cardiopulmonary reflexes and may be related to central commands and/or modifications of the dynamical properties of the sinus node.

Continuous wound infusion of local anesthetic and steroid after major abdominal surgery: study protocol for a randomized controlled trial.

BACKGROUND: Inflammatory response is one of the key components of pain perception. Continuous infusion (CWI) of local anesthetics has been shown to be effective in controlling pain and reducing postoperative morphine consumption, but the effect of adding a potent anti-inflammatory drug (such as a steroid) has never been addressed. In our study, we want to investigate the effect of CWI with local anesthetic + methylprednisolone on acute and persistent pain, correlating clinical data with biomarkers of inflammation and genetic background. METHODS/DESIGN: After approval by their institutional review board, three hospitals will enroll 120 patients undergoing major abdominal surgery in a randomized, double-blind, phase III study. After a 24-h CWI of ropivacaine 0.2 % + methylprednisolone 1 mg/kg, patients will be randomly assigned to receive either ropivacaine + steroid or placebo for the next 24 h. Then, patient-controlled CWI with only ropivacaine 0.2 % or placebo (according to the group of randomization) is planned after 48 h up to 7 days (bolus 10 ml, lock-out 1 h, maximum dose of 40 ml in 4 h). Morphine equivalent consumption up to 7 days will be analyzed, together with any catheter- or drug-related side effect. Persistent post-surgical pain (PPSP) incidence will also be investigated. Our primary endpoint is analgesic consumption in the first 7 days after surgery; we will evaluate, as secondary endpoints, any catheter- or drug-related side effect, genotype/phenotype correlations between some polymorphisms and postoperative outcome in terms of morphine consumption, development of the inflammatory response, and incidence of PPSP. Finally, we will collect, in a subgroup of patients, wound exudate samples by micro-dialysis, blood samples, and urine samples up to 72 h to investigate local and systemic inflammation and oxidative stress. DISCUSSION: This is a phase III trial to evaluate the safety and efficacy of wound infusion with steroid and local anesthetic. The study is aimed also to evaluate how long this infusion has to be maintained in order to maximize effectiveness. Our data are intended to quantify the amount of ropivacaine and methylprednisolone needed by patients undergoing major abdominal surgery, to be stored in a new nanotechnology device for sustained pain treatment after surgery. We also aim to clarify the roles of inflammatory response, oxidative stress, and genetic background on postoperative and persistent pain after major abdominal surgery. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov ( NCT02002663 ) on 24 Oct. 2013.

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.

Candidaemia observed at a university hospital in Milan (northern Italy) and review of published studies from 2010 to 2014.

BACKGROUND: Candida species represent the fourth leading cause of nosocomial bloodstream infections (BSI) worldwide. However, candidaemia rates and species involved vary geographically. OBJECTIVES: To evaluate the epidemiological pattern, risk factors for mortality and antifungal therapy of Candida BSI over a 5-year period (2008-2012) in a university hospital in northern Italy together with a review of the recent literature concerning candidaemia. METHODS: A retrospective cohort study cross-linked with microbiology database was performed. RESULTS: A total of 89 Candida BSI were identified in 42 males (47 %) and 47 females (52.8 %). The median age was 69 years (interquartile range 55-78) with 61.8 % of patients being older than 65 years. Considering all hospitalized patients, the overall incidence rate of candidaemia increased significantly from 2008 to 2012 (from 0.4 to 1.68 episodes per 10,000 patient/days) (p = 0.0001) with a mean linear increase in 5 new cases per year. Candida albicans was the predominant species isolated (64 %) followed by C. glabrata (19.1 %). The latter species was observed with significantly higher frequency in Internal Medicine and Intensive Care Units (ICU). In-hospital crude mortality was 41.6 %. CONCLUSIONS: Candidaemia is an increasing BSI in our university hospital, in accordance with that observed in northern Italy, and it is still associated with high in-hospital crude mortality.

May Renal Resistive Index be an early predictive tool of postoperative complications in major surgery? Preliminary results.

BACKGROUND: Patients who undergo high-risk surgery represent a large amount of post-operative ICU-admissions. These patients are at high risk of experiencing postoperative complications. Renal Resistive Index was found to be related with renal dysfunction, hypertension, and posttraumatic hemorrhagic shock, probably due to vasoconstriction. We explored whether Renal Resistive Index (RRI), measured after awakening from general anesthesia, could have any relationship with postoperative complications. METHODS: In our observational, stratified dual-center trial, we enrolled patients who underwent general anesthesia for high-risk major surgery. After awakening in recovery room (or during awakening period in subjects submitted to cardiac surgery) we measured RRI by echo-color-Doppler method. Primary endpoint was the association of altered RRI (>0.70) and outcome during the first postoperative week. RESULTS: 205 patients were enrolled: 60 (29.3%) showed RRI > 0.70. The total rate of adverse event was 27 (18.6%) in RRI ≤ 0.7 group and 19 (31.7%) in RRI > 0.7 group (P = 0.042). Significant correlation between RRI > 0.70 and complications resulted in pneumonia (P = 0.016), septic shock (P = 0.003), and acute renal failure (P = 0.001) subgroups. Patients with RRI > 0.7 showed longer ICU stay (P = 0.001) and lasting of mechanical ventilation (P = 0.004). These results were confirmed in cardiothoracic surgery subgroup. RRI > 0.7 duplicates triplicates the risk of complications, both in general (OR 2.03 93 95% CI 1.02-4.02, P = 0.044) and in cardiothoracic (OR 2.62 95% CI 1.11-6.16, P = 0.027) population. Furthermore, we found RRI > 0.70 was associated with a triplicate risk of postoperative septic shock (OR 3.04, CI 95% 1.5-7.01; P = 0.002).

Directionality in cardiovascular variability interactions during head-down tilt test.

A nonlinear model-free Granger causality approach was exploited to quantify the strength of the causal relation along cardiac baroreflex and cardiopulmonary pathway from spontaneous cardiovascular variabilities during head-down tilt (HDT). The analysis was completed through the assessment of traditional time and frequency domain parameters and cardiac baroreflex sensitivity. We found that, while respiratory sinus arrhythmia augmented, the power of the systolic arterial pressure variability in the low frequency band (i.e. from 0.04 to 0.15 Hz) decreased and cardiac baroreflex sensitivity increased, the strength of the causal relation along cardiac baroreflex and cardiopulmonary pathway remained constant. We conclude that, despite cardiopulmonary stimulation and sympathetic inhibition induced by HDT, neither cardiac baroreflex nor cardiopulmonary pathway took prevalence in governing heart period changes during HDT.

Comparison of the Surgical Pleth Index with autonomic nervous system modulation on cardiac activity during general anaesthesia: A randomised cross-over study.

BACKGROUND: Surgical plethysmographic index (SPI) has been proposed as a tool to measure the nociception/antinociception balance during general anaesthesia. Untreated nociception may increase sympathetic tone, but the relationship between SPI and the autonomic nervous system (ANS) is poorly understood. OBJECTIVE: We hypothesised that two different levels of SPI might be associated with differences in ANS modulation, measured by the frequency domain analysis of heart rate variability (HRV). DESIGN: A randomised, cross-over group study, conducted between February and November 2009. SETTING: University tertiary referral hospital in Milan, Italy. PATIENTS: Forty-two adult patients undergoing scheduled laparoscopic abdominal surgery. INTERVENTIONS: ECG, noninvasive arterial blood pressure and SPI were recorded during balanced general anaesthesia with inhaled sevoflurane and intravenous remifentanil. After pneumoperitoneum induction, the remifentanil infusion rate was set to obtain two different levels of SPI (>50, HI-SPI, and <50, LO-SPI) for each patient. MAIN OUTCOME MEASURES: Arterial pressure, heart rate (HR), low-frequency and high-frequency spectral components, the low frequency/high frequency ratio (measure of sympathovagal balance) and whole power spectrum density of HRV were measured at the two different levels of SPI. RESULTS: Thirty-nine patients were included in the final analysis. During LO-SPI, HR and systolic and mean blood pressures were significantly lower than HI-SPI. The median low frequency/high frequency ratio was reduced during LO-SPI [1.29 interquartile range (IQR) 0.66 to 2.05) vs. 2.36 (1.30 to 3.62), P = 0.008]. The sensitivity analysis revealed a significant correlation between SPI changes and changes of all ANS indices, arterial pressure and HR, with a slightly better correlation for low frequency/high frequency (Spearman ρ = 0.70, IQR 0.484 to 0.834, P < 0.001). CONCLUSION: In the context of a balanced general anaesthesia in healthy patients undergoing laparoscopic abdominal surgery, ANS modulation seems to correlate with changes in SPI. Further studies are warranted to assess whether this may reflect a change in nociception/antinociception balance or a pharmacodynamic effect of remifentanil.

Profile of infective endocarditis observed from 2003 - 2010 in a single center in Italy.

BACKGROUND: This study aimed to provide a contemporary picture of the epidemiologic, clinical, microbiologic characteristics and in-hospital outcome of infective endocarditis (IE) observed in a single center in Italy. METHODS: We performed a retrospective study of patients with definite or probable IE observed at the "L. Sacco" Hospital in Milan, Italy, from January 1, 2003 through December 31, 2010. RESULTS: 189 episodes of IE in 166 patients were included. The mean number of incident IE in the study period was of 1.27 (range 0.59-1.76) cases per 1000 patients admitted. The median age of the cohort was 57 (interquartile range, 43-72) years, 63% were male and 62.5% had native valve IE. Twenty-six percent were active intravenous drug users (IVDU), 29% had a health care-associated IE and 5% chronic rheumatic disease. Twenty-nine percent of the cases occurred in patients affected by chronic liver disease and 19% in HIV positive subjects. Staphylococcus aureus was the most common pathogen (30%), followed by streptococci. The mitral (34%) and aortic (31%) valves were involved most frequently. The following complications were common: stroke (19%), non-stroke embolizations (25%), heart failure (26%) and intracardiac abscess (9%). Surgical treatment was frequently employed (52%) but in hospital mortality remained high (17%). Health care-associated IE and complications were independently associated with an increased risk of in-hospital death, while surgery was associated with decreased mortality. CONCLUSION: S. aureus emerged as the leading causative organism of IE in a University hospital in northern Italy. Our study confirmed the high in-hospital mortality of IE, particularly if health care associated, and the protective role of surgery.