This article is drafted as a consensus document involving eight members of the Italian Society of Clinical Biochemistry and Laboratory Medicine (SIBioC) and eight members of the Academy of Emergency Medicine and Care (AcEMC), to whom a questionnaire was submitted for obtaining opinions on some recommendations about the use of biomarkers for diagnosing sepsis and managing antibiotic therapy in the emergency department. These recommendations were drafted following the National Guidelines Program (PNLG). According to the cumulative consent, three "A" recommendations (strongly recommended indication) emerged, which include biomarker availability (always available on prescription), clinical use (always interpreted in according to clinical data) and timing of the request based on half-life of the analyte. Recommendations of type "B" (indications carefully considered) included a general agreement about the clinical usefulness of sepsis biomarkers, the combination of procalcitonin (PCT) and C-reactive protein (CRP), the possibility to be free on prescription to the laboratory, the use of cut-offs favoring a high negative predictive value, the use of more analytically sensitive assays and the possibility of using PCT for monitoring antibiotic therapy, with timing of ordering defined according to the metabolism of the analyte. As regards the specific biomarkers, a similar "B" consensus has been reached for measuring both PCT and CRP, and for measuring lactic acid. The measurement of other biomarkers is discouraged except for presepsin, for which there is still substantial uncertainty in favor or against.

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.

Controlled breathing maneuver is being widely applied for cardiovascular autonomic control evaluation and cardiac vagal activation through reduction of breathing rate (BR). However, this maneuver presented contradictory results depending on the protocol and the chosen BR. These variations may be related to the individual intrinsic profile baseline sympathetic tonus, as described before by others. In this study, we evaluated the effect of controlled breathing maneuver on cardiovascular autonomic control in 26 healthy subjects allocated into two protocols: (1) controlled breathing in three different rates (10, 15, and 20 breaths/min) and (2) controlled breathing in rates normalized by the individual spontaneous breathing rate (SBR) at 100, 80, 70, and 50%. Our results showed autonomic responses favorable to vagal modulation with the lower BR maneuvers. Nevertheless, while this activation was variable using the standard protocol, all participants of the normalized protocol demonstrated an increase of vagal modulation at 80% BR (HFnu 80 = 67.5% vs. 48.2%, p < 0.0001). These results suggest that controlled breathing protocols to induce vagal activation should consider the SBR, being limited to values moderately lower than the baseline.

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.

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.

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.

Increasing evidence is emerging that the measurement of circulating biomarkers may be clinically useful for diagnosing and monitoring sepsis. Eight members of AcEMC (Academy of Emergency Medicine and Care) and eight members of SIBioC (Italian Society of Clinical Biochemistry and Laboratory Medicine) were identified by the two scientific societies for producing a consensus document aimed to define practical recommendations about the use of biomarkers for diagnosing of sepsis and managing antibiotic therapy in the emergency department (ED). The cumulative opinions allowed defining three grade A recommendations (i.e., highly recommended indications), entailing ordering modality (biomarkers always available on prescription), practical use (results should be interpreted according to clinical information) and test ordering defined according to biomarker kinetics. Additional grade B recommendations (i.e., potentially valuable indications) entailed general agreement that biomarkers assessment may be of clinical value in the diagnostic approach of ED patients with suspected sepsis, suggestion for combined assessment of procalcitonin (PCT) and C-reactive protein (CRP), free availability of the selected biomarker(s) on prescription, adoption of diagnostic threshold prioritizing high negative predictive value, preference for more analytically sensitive techniques, along with potential clinical usefulness of measuring PCT for monitoring antibiotic treatment, with serial testing defined according to biomarker kinetics. PCT and CRP were the two biomarkers that received the largest consensus as sepsis biomarkers (grade B recommendation), and a grade B recommendation was also reached for routine assessment of blood lactate. The assessment of biomarkers other than PCT and CRP was discouraged, with exception of presepsin for which substantial uncertainty in favor or against remained.

Emergency departments (EDs) are increasingly used for patients at the end of life stage of their diseases worldwide, even if they do not have acute and potentially treatable conditions. Moreover, an increasingly shortage of hospital beds, in spite of the wellrecognized ageing of the population, has led to a progressive prolongation of the average length of stay (LOS) time in the vast majority of Italians EDs. Therefore, the aim of this study was to describe the trend of ED non-traumatic deaths in 11 Italians EDs, and to correlate these deaths with the medium length of stay in the same EDs. All cases classified as “died during ambulance transfer or while in the ED” have been retrieved from the hospital database of the 11 participating EDs, from January 1st 2007 to December 31st 2016, with the exclusion of traumatic events. The average LOS in minutes of the seven hospitals that could provide this information was then calculated. A continuously increasing number of ED deaths was observed in the vast majority of participating EDs, showing a nearly 30% increases in the last four years. The average LOS of the vast majority of participating hospitals displayed a significant increase during the observational period. We also found a linear correlation between average LOS and total number of ED deaths in the same seven hospitals. We believe that there is a compelling need to reconsider the end of life trajectories, not only under an economical perspective, but mainly according to a more ethical view.

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.

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.

General anesthesia attenuates autonomic function and baroreflex control. This side effect should be prevented as much as possible because it limits the subject's ability in responding to physiological challenges during surgery (e.g. arterial pressure and ventricular contractility drops). This study is designed to rank two of the most commonly exploited general anesthesia treatments, i.e. intravenous anesthesia (IA) based on a propofol-opioid combination and volatile anesthesia (VA) based on a sevoflurane-opioid combination, according to their ability to maintain autonomic nervous system activity and baroreflex control. Univariate and bivariate symbolic techniques were applied to spontaneous heart period (HP) and systolic arterial pressure (SAP) variability series recorded during IA and VA procedures in 19 and 18 patients undergoing elective intracranial neurosurgery. Traditional linear univariate and bivariate frequency domain markers of the autonomic nervous system state and baroreflex control were evaluated as well. We found that: (i) univariate symbolic analysis of HP series suggests a better preservation of vagal modulation in VA than in IA; (ii) bivariate symbolic markers assessing the degree of HP-SAP association differentiate IA from VA, while baroreflex sensitivity and squared coherence function cannot; (iii) bivariate symbolic analysis indicates a better preservation of the HP-SAP association at slow frequencies in IA than in VA, thus suggesting a more active baroreflex control in IA. We conclude that symbolic indexes can be fruitfully exploited to rank general anesthesia treatments, and their performance appears to be superior to that of more traditional linear markers.

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.

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 degrees-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.

The hypothesis that central volume plays a key role in the source of low frequency (LF) oscillations of heart rate variability (HRV) was tested in a population of end stage renal disease patients undergoing conventional hemodialysis (HD) treatment, and thus subject to large fluid shifts and sympathetic activation. Fluid overload (FO) in 58 chronic HD patients was assessed by whole body bioimpedance measurements before the midweek HD session. Heart Rate Variability (HRV) was measured using 24-hour Holter electrocardiogram recordings starting before the same HD treatment. Time domain and frequency domain analyses were performed on HRV signals. Patients were retrospectively classified in three groups according to tertiles of FO normalized to the extracellular water (FO/ECW%). These groups were also compared after stratification by diabetes mellitus. Patients with the low to medium hydration status before the treatment (i.e. 1st and 2nd FO/ECW% tertiles) showed a significant increase in LF power during last 30 min of HD compared to dialysis begin, while no significant change in LF power was seen in the third group (i.e. those with high pre-treatment hydration values). In conclusion, several mechanisms can generate LF oscillations in the cardiovascular system, including baroreflex feedback loops and central oscillators. However, the current results emphasize the role played by the central volume in determining the power of LF oscillations.

The study compares permutation-based and coarse-grained entropy approaches for the assessment of complexity of short heart period (HP) variability recordings. Shannon permutation entropy (SPE) and conditional permutation entropy (CPE) are computed as examples of permutation-based entropies, while the k-nearest neighbor conditional entropy (KNNCE) is calculated as an example of coarse-grained conditional entropy. SPE, CPE and KNNCE were applied to ad-hoc simulated autoregressive processes corrupted by increasing amounts of broad band noise and to real HP variability series recorded after complete vagal blockade obtained via administration of a high dose of atropine (AT) in nine healthy volunteers and during orthostatic challenge induced by 90° head-up tilt (T90) in 15 healthy individuals. Over the simulated series the performances of SPE and CPE degraded more rapidly with the amplitude of the superimposed broad band noise than those of KNNCE. Over real data KNNCE identified the expected decrease of the HP variability complexity both after AT and during T90. Conversely SPE and CPE detected the decrease of HP variability complexity solely during T90 as a likely result of the more favorable signal-to-noise ratio during T90 than after AT. Results derived from both simulations and real data indicated that permutation-based entropies had a larger susceptibility to broad band noise than KNNCE. We recommend caution in applying permutation-based entropies in presence of short HP variability series characterized by a low signal-to-noise ratio.

Background. Studies on pregnant women undergoing cesarean delivery or elderly men scheduled for prostate brachytherapy have demonstrated the predictive value of heart rate variability (HRV) analysis for hypotension during spinal anesthesia. We conducted a prospective observational study to investigate if preoperative HRV analysis may have a role in identifying the risk of hypotension following spinal anesthesia in otherwise healthy patients.Methods. The study investigated 47 ASA physical status I-II patients aged between 18-50 years that underwent subarachnoid anesthesia for lower abdominal or orthopedic scheduled surgery. ECG was recorded from all subjects before the subarachnoid block. We analysed the autonomic nervous system modulation, measured by HRV analysis. The variables that were be considered were preoperative HRV total power, low frequency (LF) and high frequency (HF) heart beat oscillations and LF/HF ratio. The LF/HF ratio was dichotomized according to the median for sensitivity analysis.. The lowest arterial pressure value between spinal anesthesia and the end of surgery was recorded.Results. The median LF/HF before anesthesia was 2.3. We considered two groups of 23 (LF/HF<2.3, group LOW) and 24 (LF/HF>2.3, group HIGH) patients respectively. Both groups had similar baseline demographic and hemodynamic variables. A high preoperative sympathetic outflow and loss of vagal modulation, as stated by LF/HF>2.3, was correlated with a relative risk of 7.7 (95%CI 1.04 to 56.6, p=0.023) of post-spinal hypotension.Conclusions. Preoperative analysis of autonomic nervous system modulation might be useful to stratify the risk of post-spinal hypotension and it might indicate the need for careful monitoring or prophylactic fluids.

Surgical Plethysmographic Index (SPI), calculated from pulse photo-plethysmographic amplitude oscillations, has been proposed as a tool to measure nociception anti-nociception balance during general anesthesia, but it is affected by several confounding factor that alter the autonomic nervous system (ANS) modulation. We hypothesized that SPI may be mainly affected by sympathetic stimulation independently from nociception. We studied the effects of two sympathetic stimuli on SPI, delivered through passive head-up tilt at 45 and 90 degrees angles, in nine awake healthy adults. The sympathetic modulation was assessed by means of heart rate variability (HRV) analysis. Mean (SD) SPI significantly increased from baseline to 45 degrees [from 38.6 (13.7) to 60.8 (7.6), p<0.001)] and to 90 degrees angle tilt [82.3 (5.4), p<0.001]. The electrocardiographic mean R-to-R interval significantly shortened during both passive tilts, whereas systolic arterial pressure did not change during the study protocol. HRV changed significantly during the study protocol towards a predominance of sympathetic modulation during passive tilt. Gravitational sympathetic stimulation at two increasing angles, in absence of any painful stimuli, affects SPI in awake healthy volunteers. SPI seems to reflect the sympathetic outflow directed to peripheral vessels.

Background. Autonomic cardiovascular modulation during surgery might be affected by different anesthetic strategies. Aim of the present study was to assess autonomic control during three different anesthetic strategies in the course of neurosurgical procedures by the linear and non-linear analysis of two cardiovascular signals.Methods. Heart rate (EKG-RR intervals) and systolic arterial pressure (SAP) signals were analyzed in 93 patients during elective neurosurgical procedures at fixed points: anesthetic induction, dura mater opening, first and second hour of surgery, dura mater and skin closure. Patients were randomly assigned to three anesthetic strategies: sevoflurane+fentanyl (S-F), sevoflurane+remifentanil (S-R) and propofol+remifentanil (P-R).Results. All the three anesthetic strategies were characterized by a reduction of RR and SAP variability. A more active autonomic sympathetic modulation, as ratio of low to high frequency spectral components of RR variability (LF/HF), was present in the P-R group vs. S-R group. This is confirmed by non-linear symbolic analysis of RR series and SAP variability analysis. In addition, an increased parasympathetic modulation was suggested by symbolic analysis of RR series during the second hour of surgery in S-F group.Conclusion. Despite an important reduction of cardiovascular signal variability, the analysis of RR and SAP signals were capable to detect information about autonomic control during anesthesia. Symbolic analysis (non-linear) seems to be able to highlight the differences of both the sympathetic (slow) and vagal (fast) modulation among anesthetics, while spectral analysis (linear) underlines the same differences but only in terms of balance between the two neural control systems.

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.

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.