Observational study on passive leg raising and the autonomic nervous system.

In the intensive care and perioperative setting, circulation is often supported by intravenous fluid preceded by prediction of fluid responsiveness during a passive leg raising (PLR) maneuver. An increase in stroke volume (SV) or cardiac output (CO) of 10%-15% indicates that the subject may increase the flow upon volume expansion. However, the semi-recumbent position as an initial position in PLR likely reduces SV by gravitational displacement of central blood volume (CBV) to lower extremities, thereby accentuating volume responsiveness during leg raising in healthy people. Coincident with gravitational perturbations in hemodynamics, remedial changes occur in the autonomic nervous system (ANS), as expressed in spectral power in heart rate variability (HRV). This study aims to clarify these concomitant changes during PLR. A convenience number of healthy volunteers (N = 11) were recruited by advertisement in university departments. The subjects were exposed to the established PLR sequence and the heart rate (HR), mean arterial pressure (MAP), SV, and CO were sampled at 1 Hz, while electrocardiogram was recorded at 1000 Hz. Relative powers reflecting autonomic nervous system activity were assessed from spectral analysis of HRV. In response to PLR, SV increased (12.4% ± 8.7%, p < 0.0026), while HR (-7.6% ± 4.7%, p < 0.0009) and MAP (-7.6% ± 6.9%, p < 0.01) decreased, with no change in CO (4.1% ± 12.8%, ns). The HRV low-frequency component was reduced (-34%; p < 0.0095), while the high-frequency activity increased (78.5%; p < 0.0013), with a 63% decrease in the low/high frequency ratio (p < 0.0078). Thus, HRV indicated a reduced sympathetic index (semi-recumbent 0.808 vs. PLR -0.177 a.u., p < 0.001) and an increased parasympathetic index (-0.141 to 0.996 a.u., p < 0.0001). Gravitational depletion and expansion of CBV during PLR were associated with a counterregulatory autonomic response. Healthy volunteers appeared volume responsive in terms of SV, but not CO. Responses to PLR are influenced by the ANS, and HRV analysis should be included in the assessment of the PLR test.

Experimental validation of a mean systemic pressure analog against zero-flow measurements in porcine VA-ECMO.

The mean systemic pressure analog (Pmsa), calculated from running hemodynamic data, estimates mean systemic filling pressure (MSFP). This post hoc study used data from a porcine veno-arterial extracorporeal membrane oxygenation (ECMO) model [n = 9; Sus scrofa domesticus; ES breed (Schweizer Edelschwein)] with eight experimental conditions; Euvolemia [a volume state where ECMO flow produced normal mixed venous saturation (SVO2) without vascular collapse]; three levels of increasing norepinephrine infusion (Vasoconstriction 1-3); status after stopping norepinephrine (Post Vasoconstriction); and three steps of volume expansion (10 mL/kg crystalloid bolus) (Volume Expansion 1-3). In each condition, Pmsa and a "reduced-pump-speed-Pmsa" (Pmsared) were calculated from baseline and briefly reduced pump speeds, respectively. We calculated agreement for absolute values (per condition) and changes (between consecutive conditions) of Pmsa and Pmsared, against MSFP at zero ECMO flow. Euvolemia venous return driving pressure was 5.1 ± 2.0 mmHg. Bland-Altman analysis for Pmsa vs. MSFP (all conditions; 72 data pairs) showed bias (confidence interval) 0.5 (0.1-0.9) mmHg; limits of agreement (LoA) -2.7 to 3.8 mmHg. Bias for ΔPmsa vs. ΔMSFP (63 data pairs): 0.2 (-0.2 to 0.6) mmHg, LoA -3.2 to 3.6 mmHg. Bias for Pmsared vs. MSFP (72 data pairs): 0.0 (-0.3 to -0.3) mmHg; LoA -2.3 to 2.4 mmHg. Bias for ΔPmsared vs. ΔMSFP (63 data pairs) was 0.2 (-0.1 to 0.4) mmHg; LoA -1.8 to 2.1 mmHg. In conclusion, during veno-arterial ECMO, under clinically relevant levels of vasoconstriction and volume expansion, Pmsa accurately estimated absolute and changing values of MSFP, with low between-method precision. The within-method precision of Pmsa was excellent, with a least significant change of 0.15 mmHg.NEW & NOTEWORTHY This is the first study ever to validate the mean systemic pressure analog (Pmsa) against the reference mean systemic filling pressure (MSFP) determined at full arterio-venous pressure equilibrium. Using a porcine ECMO model with clinically relevant levels of vasoconstriction and volume expansion, we showed that Pmsa accurately estimated absolute and changing values of MSFP, with a poor between-method precision. The within-method precision of Pmsa was excellent.

A retrospective study of 251 patients admitted to a multidisciplinary, neurorehabilitation unit with intensive care unit capabilities.

Introduction: In Denmark, specialised neurorehabilitation is centralised in two centres; one is Hammel Neurocentre. The neurointensive stepdown unit at Silkeborg Regional Hospital offers intensive care in addition to specialised neurorehabilitation of patients transferring to Hammel. Knowledge on patient's characteristics and course of rehabilitation in this kind of setting is sparse.Objective: To characterise the patients, their change in function and to identify variables associated with referral time to Hammel.Methods: Functional scores and available covariates were extracted from hospital records on 251 patients admitted from 01 November 2011 to 31 July 2016. Statistical methods included logistic regression and paired tests.Results: Mean (standard deviation) time from injury to admission at the neurointensive stepdown unit was 30 (22) d, medians (interquartile range) of Functional Independence Measure and Early Functional Abilities increased significantly from 18 (18, 19) to 24 (18, 44) and 37 (30, 46) to 52 (43, 70), respectively, during admission (p < 0.01). Spontaneous ventilation and Early Functional Abilities score on admission were positively associated with early referral. Obesity and anoxic brain injury were negatively associated with early referral.Conclusions: This study demonstrated functional improvement in patients in a neurointensive stepdown unit and identified variables associated with early referral. The study indicated higher sensitivity of the Early Functional Abilities score as compared to the Functional Independence Measure.Implications for rehabilitationPatients requiring prolonged intensive care services after severe acquired brain injury may require the fusion of neurorehabilitation and intensive care services to benefit maximally.There is a need for a consensus on which functional scores to use when documenting functional level and functional changes in patients with severe acquired brain injury and very low functional levels.The Early Functional Abilities score is an example of a valuable tool when assessing functional levels of patients with severe acquired brain injury and very low functional levels.

Effect of volume status on the estimation of mean systemic filling pressure.

Various methods for indirect assessment of mean systemic filling pressure (MSFP) produce controversial results compared with MSFP at zero blood flow. We recently reported that the difference between MSFP at zero flow measured by right atrial balloon occlusion (MSFPRAO) and MSFP estimated using inspiratory holds depends on the volume status. We now compare three indirect estimates of MSFP with MSFPRAO in euvolemia, bleeding, and hypervolemia in a model of anesthetized pigs (n = 9) with intact circulation. MSFP was estimated using instantaneous beat-to-beat venous return during tidal ventilation (MSFPinst_VR), right atrial pressure-flow data pairs at flow nadir during inspiratory holds (MSFPnadir_hold), and a dynamic model analog adapted to pigs (MSFPa). MSFPRAO was underestimated by MSFPnadir_hold and MSFPa in all volume states. Volume status modified the difference between MSFPRAO and all indirect methods (method × volume state interaction, P ≤ 0.020). All methods tracked changes in MSFPRAO concordantly, with the lowest bias seen for MSFPa [bias (confidence interval): -0.4 (-0.7 to -0.0) mmHg]. We conclude that indirect estimates of MSFP are unreliable in this experimental setup. NEW & NOTEWORTHY For indirect estimations of MSFP using inspiratory hold maneuvers, instantaneous beat-to-beat venous return, or a dynamic model analog, the accuracy was affected by the underlying volume state. All methods investigated tracked changes in MSFPRAO concordantly.

Variability in alignment of central venous pressure transducer to physiologic reference point in the intensive care unit-A descriptive and correlational study.

BACKGROUND: The phlebostatic axis is the most commonly used anatomical external reference point for central venous pressure measurements. Deviation in the central venous pressure transducer alignment from the phlebostatic axis causes inadequate pressure readings, which may affect treatment decisions for critically ill patients in intensive care units. AIM: The primary aim of the study was to assess the variability in central venous pressure transducer levelling in the intensive care unit. We also assessed whether patient characteristics impacted on central venous pressure transducer alignment deviation. METHODS: A sample of 61 critical care nurses was recruited and asked to place a transducer at the appropriate level for central venous pressure measurement. The measurements were performed in the intensive care unit on critically ill patients in supine and Fowler's positions. The variability among the participants using eyeball levelling and a laser levelling device was calculated in both sessions and adjusted for patient characteristics. RESULTS: A significant variation was found among critical care nurses in the horizontal levelling of the pressure transducer placement when measuring central venous pressure in the intensive care unit. Using a laser levelling device did not reduce the deviation from the phlebostatic axis. Patient characteristics had little impact on the deviation in the measurements. CONCLUSION: The anatomical external landmark for the phlebostatic axis varied between critical care nurses, as the variation in the central venous pressure transducer placement was not reduced with a laser levelling device. Standardisation of a zero-level for vascular pressures should be considered to reduce the variability in vascular pressure readings in the intensive care unit to improve patient treatment decisions. Further studies are needed to evaluate critical care nurses' knowledge and use of central venous pressure monitoring and whether assistive tools and/or routines can improve the accuracy in vascular pressure measurements in intensive care units.

Mannitol clearance for the determination of glomerular filtration rate-a validation against clearance of 51 Cr-EDTA.

We studied the agreement between plasma clearance of mannitol and the reference method, plasma clearance of 51 Cr-EDTA in outpatients with normal to moderately impaired renal function. Forty-one patients with a serum creatinine <200 µmol l-1 entered the study. 51 Cr-EDTA clearance was measured with the standard bolus injection technique and glomerular filtration rate (GFR) was calculated by the single-sample method described by Jacobsson. Mannitol, 0·25 g kg-1 body weight (150 mg ml-1 ), was infused for 4-14 min and blood samples taken at 1-, 2-, 3- and 4-h (n = 24) or 2-, 3-, 3·5- and 4-h after infusion (n = 17). Mannitol in serum was measured by an enzymatic method. Plasma clearance for mannitol and its apparent volume of distribution (Vd) were calculated according to Brøchner-Mortensen. Mean plasma clearance (±SD) for 51 Cr-EDTA was 59·7 ± 18·8 ml min-1 . The mean plasma clearance for mannitol ranged between 57·0 ± 20·1 and 61·1 ± 16·7 ml min-1 and Vd was 21·3 ± 6·2% per kg b.w. The between-method bias ranged between -0·23 and 2·73 ml min-1 , the percentage error between 26·7 and 39·5% and the limits of agreement between -14·3/17·2 and -25·3/19·9 ml min-1 . The best agreement was seen when three- or four-sample measurements of plasma mannitol were obtained and when sampling started 60 min after injection. Furthermore, accuracy of plasma clearance determinations was 88-96% (P30) and 41-63% (P10) and was highest when three- or four-sample measurements of plasma mannitol were obtained, including the first hour after the bolus dose. We conclude that there is a good agreement between plasma clearances of mannitol and 51 Cr-EDTA for the assessment of GFR.

Right atrial pressure and venous return during cardiopulmonary bypass.

The relevance of right atrial pressure (RAP) as the backpressure for venous return (QVR) and mean systemic filling pressure as upstream pressure is controversial during dynamic changes of circulation. To examine the immediate response of QVR (sum of caval vein flows) to changes in RAP and pump function, we used a closed-chest, central cannulation, heart bypass porcine preparation (n = 10) with venoarterial extracorporeal membrane oxygenation. Mean systemic filling pressure was determined by clamping extracorporeal membrane oxygenation tubing with open or closed arteriovenous shunt at euvolemia, volume expansion (9.75 ml/kg hydroxyethyl starch), and hypovolemia (bleeding 19.5 ml/kg after volume expansion). The responses of RAP and QVR were studied using variable pump speed at constant airway pressure (PAW) and constant pump speed at variable PAW Within each volume state, the immediate changes in QVR and RAP could be described with a single linear regression, regardless of whether RAP was altered by pump speed or PAW (r2 = 0.586-0.984). RAP was inversely proportional to pump speed from zero to maximum flow (r2 = 0.859-0.999). Changing PAW caused immediate, transient, directionally opposite changes in RAP and QVR (RAP: P ≤ 0.002 and QVR: P ≤ 0.001), where the initial response was proportional to the change in QVR driving pressure. Changes in PAW generated volume shifts into and out of the right atrium, but their effect on upstream pressure was negligible. Our findings support the concept that RAP acts as backpressure to QVR and that Guyton's model of circulatory equilibrium qualitatively predicts the dynamic response from changing RAP.NEW & NOTEWORTHY Venous return responds immediately to changes in right atrial pressure. Concomitant volume shifts within the systemic circulation due to an imbalance between cardiac output and venous return have negligible effects on mean systemic filling pressure. Guyton's model of circulatory equilibrium can qualitatively predict the resulting changes in dynamic conditions with right atrial pressure as backpressure to venous return.

Identifying the position of the right atrium to align pressure transducer for CVP : Spirit level or 3D electromagnetic positioning?

The central venous pressure, CVP, is an important variable in the management of selected perioperative and intensive care cases and in clinical decision support systems, CDSS. In current routine, when measuring CVP the health care provider may use anatomical landmarks and a spirit level, SL, to adjust the pressure transducer to the level of the tricuspid valve, i.e. the phlebostatic axis. The aim of the study was to assess the agreement in the postoperative setting between the SL method and electromagnetic 3D positioning (EM). CVP was measured with patients in positions dictated by nursing routines. The staff members measured CVP using SL to position the transducer at the perceived phlebostatic level. This position was compared to coordinates based on an electromagnetic field with external sensors at anatomical landmarks and an internal sensor in the CV catheter for 3D determination of the phlebostatic axis. An electronic survey took bearing on the accepted error in measurement among colleagues at the department. There was a clinically relevant difference between the CVP measured by the staff members and the CVP based on the 3D EM positioning. The limits of agreement extended in excess of ±8 mmHg and half of the measurements had deviations outside an accepted error range of ±2.5 mmHg. There was a large variation in CVP measurements when assessing the agreement with the current method. This may indicate the need for improvement in accuracy, e.g. using the electromagnetic field positioning system, in association with routine monitoring and clinical decision support systems.

Effect of PEEP, blood volume, and inspiratory hold maneuvers on venous return.

According to Guyton's model of circulation, mean systemic filling pressure (MSFP), right atrial pressure (RAP), and resistance to venous return (RVR) determine venous return. MSFP has been estimated from inspiratory hold-induced changes in RAP and blood flow. We studied the effect of positive end-expiratory pressure (PEEP) and blood volume on venous return and MSFP in pigs. MSFP was measured by balloon occlusion of the right atrium (MSFPRAO), and the MSFP obtained via extrapolation of pressure-flow relationships with airway occlusion (MSFPinsp_hold) was extrapolated from RAP/pulmonary artery flow (QPA) relationships during inspiratory holds at PEEP 5 and 10 cmH2O, after bleeding, and in hypervolemia. MSFPRAO increased with PEEP [PEEP 5, 12.9 (SD 2.5) mmHg; PEEP 10, 14.0 (SD 2.6) mmHg, P = 0.002] without change in QPA [2.75 (SD 0.43) vs. 2.56 (SD 0.45) l/min, P = 0.094]. MSFPRAO decreased after bleeding and increased in hypervolemia [10.8 (SD 2.2) and 16.4 (SD 3.0) mmHg, respectively, P < 0.001], with parallel changes in QPA Neither PEEP nor volume state altered RVR (P = 0.489). MSFPinsp_hold overestimated MSFPRAO [16.5 (SD 5.8) vs. 13.6 (SD 3.2) mmHg, P = 0.001; mean difference 3.0 (SD 5.1) mmHg]. Inspiratory holds shifted the RAP/QPA relationship rightward in euvolemia because inferior vena cava flow (QIVC) recovered early after an inspiratory hold nadir. The QIVC nadir was lowest after bleeding [36% (SD 24%) of preinspiratory hold at 15 cmH2O inspiratory pressure], and the QIVC recovery was most complete at the lowest inspiratory pressures independent of volume state [range from 80% (SD 7%) after bleeding to 103% (SD 8%) at PEEP 10 cmH2O of QIVC before inspiratory hold]. The QIVC recovery thus defends venous return, possibly via hepatosplanchnic vascular waterfall.

Central venous pressure: soon an outcome-associated matter.

PURPOSE OF REVIEW: Central venous pressure (CVP) alone has so far not found a place in outcome prediction or prediction of fluid responsiveness. Improved understanding of the interaction between mean systemic pressure (Pms) and CVP has major implications for evaluating volume responsiveness, heart performance and potentially patient outcomes. RECENT FINDINGS: The literature review substantiates that CVP plays a decisive role in causation of operative haemorrhage and renal failure. The review details CVP as a variable integral to cardiovascular control in its dual role of distending the diastolic right ventricle and opposing venous return. SUMMARY: The implication for practice is in the regulation of the circulation. It is demonstrated that control of the blood pressure and cardiac output/venous return calls upon regulation of the volume state (Pms), the heart performance (Eh) and the systemic vascular resistance. Knowledge of the CVP is required to calculate all three.

Applying mean systemic filling pressure to assess the response to fluid boluses in cardiac post-surgical patients.

PURPOSE: To evaluate an analogue of mean systemic filling pressure (P(msa)) and derived variables to quantitatively assess the effectiveness of volume expansion in increasing cardiac output. METHODS: Sixty-one cardiac post-surgical patients were studied and 107 fluid boluses were captured. Cardiac output, mean arterial pressure and right atrial pressure were recorded with P msa before and after a bolus fluid. An increase in cardiac output greater than 10 % following a fluid bolus defined a patient as a responder. Cardiac power (i.e. the product of arterial pressure and cardiac output) and P(msa) to right atrial pressure gradient (i.e. the driving pressure for venous return and hence cardiac output) were evaluated to assess the efficiency of volume expansion to increase cardiac output. Cardiac power relative to P(msa) (CP(vol)), its dynamic changes and the dynamic changes in P msa-right atrial pressure gradient relative to the P(msa) change (E(vol)) were investigated. RESULTS: CP(vol) was lower and E(vol) was higher in responders vs. non-responders. Furthermore, in patients receiving a second fluid bolus, E(vol) correlated with the degree of increase in cardiac output. Multivariate regression analysis identified both CP(vol) and E(vol) as independent variables associated with volume responsiveness. CONCLUSIONS: Using an algorithm to derive a mean systemic filling pressure analogue, cardiac power and dynamic measures of the venous return pressure gradient relative to the mean systemic filling pressure provided an assessment of the efficiency of volume expansion in post-surgical cardiac patients.

Improved consistency in interpretation and management of cardiovascular variables by intensive care staff using a computerised decision-support system.

OBJECTIVE: To investigate the potential of a computerised decision-support system (CDSS) to improve consistency of haemodynamic evaluation and treatment suggestions by intensive care unit clinical staff with different levels of expertise and experience. DESIGN, SETTING AND PARTICIPANTS: Prospective observational study in a tertiary general ICU, of 20 patients admitted after elective cardiac surgery and assessed by staff specialists, senior registrars, registrars and nurses. MAIN OUTCOME MEASURES: A CDSS was used to display key cardiovascular variables, including mean systemic filling pressure analogue (Pmsa), heart efficiency (Eh) and vascular resistance (SVR). Staff were asked to score Pmsa, Eh and SVR ranging from -5 (grossly subnormal) through 0 (normal) to 5 (grossly supranormal), first without and then with access to the CDSS. Recommendations for therapeutic interventions were recorded. Maximal differences (diffmax) and the proportion of minimal disagreement (diffmin) between staff were evaluated. RESULTS: Without use of the CDSS, Pmsa was commonly underestimated, Eh was overestimated, and there was no clear trend for SVR, compared with estimations using the CDSS. Diffmax was reduced and diffmin was increased after access to the CDSS. Agreement between all categories of staff on therapeutic interventions increased from four to 18 patients after access to the CDSS. CONCLUSION: Use of a CDSS significantly improved the consistency between categories of clinical ICU staff in assessing the cardiovascular status and making management decisions in postoperative cardiac surgery patients.

Can baroreflex sensitivity and heart rate variability predict late neurological outcome in patients with traumatic brain injury?

BACKGROUND: Previous studies have suggested that depressed heart rate variability (HRV) and baroreflex sensitivity (BRS) are associated with early mortality and morbidity in patients with acute brain injuries of various etiologies. The aim of the present study was to assess changes in HRV and BRS in isolated traumatic brain injury (TBI), with the hypothesis that measurement of autonomic nervous system dysfunction can provide prognostic information on late neurological outcome. MATERIALS AND METHODS: Nineteen patients with TBI, requiring mechanical ventilation, sedation and analgesia, and with arterial and intracranial pressure monitoring for at least 1 week, were included. Physiological and treatment variables were collected and power spectral analyses of HRV and BRS analyses in time domain were performed daily. HRV in the high-frequency (HF) and low-frequency (LF) domains, as well as LF/HF ratio and total power, were investigated. The power of these variables to predict poor (Glasgow Outcome Scale Extended [GOSE] score <5), late (1 y) neurological outcome was assessed. RESULTS: Total power, LF, HF, and BRS were all significantly depressed in patients with GOSE score <5. This difference could not be explained by a more severe brain injury at admission or more extensive use of sedative or analgesic drugs. The autonomic variables predicted the late neurological outcome with areas under the receiver-operating curves between 0.78 and 0.83 (sensitivity: 0.63 to 0.88 and specificity: 0.73 to 0.82). CONCLUSIONS: HRV and BRS measures in TBI patients during intensive care treatment, including sedative, analgesic, and vasoactive drugs, may identify patients with poor late neurological outcome.

Pavane for a pulse pressure variation defunct.

Hemodynamic management of critically ill patients in the ICU or high-risk patients in the operating room has paradoxically shown progress in terms of outcome after the systematic application of volume responsiveness/flow optimization based on pulse pressure variation and/or stroke volume variation during controlled, positive-pressure ventilation in patients without spontaneous respiratory efforts. This assessment of circulatory optimization should ideally be based on an exhaustive, predictive and coherent physiological understanding of the cardiovascular system model. This paper sketches the extremely complex physiological background of the concept of volume responsiveness, concluding that it is not a reliable means of guiding hemodynamic optimization because it is based on a nonexhaustive, nonpredictive and incoherent physiological model.