Changes in portal pulsatility index induced by a fluid challenge in patients with haemodynamic instability and systemic venous congestion: a prospective cohort study

To evaluate the accuracy of central venous-to-arterial carbon dioxide partial pressure difference (Pcv-aCO2) before and after rapid rehydration test (fluid challenge) in predicting the fluid responsiveness in patients with septic shock. A prospective observation was conducted. Forty septic shock patients admitted to medical intensive care unit (ICU) of Peking Union Medical College Hospital from October 2015 to June 2017 were enrolled. All of the patients received fluid challenge in the presence of invasive hemodynamic monitoring. Heart rate (HR), blood pressure, cardiac index (CI), Pcv-aCO2 and other physiological variables were recorded at 10 minutes before and immediately after fluid challenge. Fluid responsiveness was defined as an increase in CI greater than 10% after fluid challenge, whereas fluid non-responsiveness was defined as no increase or increase in CI less than 10%. The correlation between Pcv-aCO2 and CI was explored by Pearson correlation analysis. Receiver operating characteristic (ROC) curves were established to evaluate the discriminatory abilities of baseline and the changes after fluid challenge in Pcv-aCO2 and other physiological variables to define the fluid responsiveness. The patients were separated into two groups according to the initial value of Pcv-aCO2. The cut-off value of 6 mmHg (1 mmHg = 0.133 kPa) was chosen according to previous studies. The discriminatory abilities of baseline and the change in Pcv-aCO2 (ΔPcv-aCO2) were assessed in each group. A total of 40 patients were finally included in this study. Twenty-two patients responded to the fluid challenge (responders). Eighteen patients were fluid non-responders. There was no significant difference in baseline physiological variable between the two groups. Fluid challenge could increase CI and blood pressure significantly, decrease HR notably and had no effect on Pcv-aCO2 in fluid responders. In non-responders, blood pressure was increased significantly and CI, HR, Pcv-aCO2 showed no change after fluid challenge. Pcv-aCO2 was comparable in responders and non-responders. In 40 patients, CI and Pcv-aCO2 was inversely correlated before fluid challenge (r = -0.391, P = 0.012) and the correlation between them weakened after fluid challenge (r = -0.301, P = 0.059). There was no significant correlation between the changes in CI and Pcv-aCO2 after fluid challenge (r = -0.164, P = 0.312). The baseline Pcv-aCO2 and ΔPcv-aCO2 could not discriminate between responders and non-responders, with the area under ROC curve (AUC) of 0.50 [95% confidence interval (95%CI) = 0.32-0.69] and 0.51 (95%CI = 0.33-0.70), respectively. HR and blood pressure before fluid challenge and their changes after fluid challenge showed very poor discriminative performances. Before fluid challenge, 16 patients had a Pcv-aCO2 > 6 mmHg. Their mean CI was significantly lower and Pcv-aCO2 was significantly higher than that in 24 patients whose Pcv-aCO2 ≤ 6 mmHg [n = 24; CI (mL×s-1×m-2): 48.3±11.7 vs. 65.0±18.3, P < 0.01; Pcv-aCO2 (mmHg): 8.4±1.9 vs. 2.9±2.8, P < 0.01]. Pcv-aCO2 was decreased significantly after fluid challenge in patients with an initial Pcv-aCO2 > 6 mmHg and their ΔPcv-aCO2 was notably different as compared with the patients whose baseline Pcv-aCO2 ≤ 6 mmHg (mmHg: -3.8±3.4 vs. 0.9±2.9, P < 0.01). 68.8% (11/16) patients responded to the fluid challenge in patients with an initial Pcv-aCO2 > 6 mmHg. The AUC of the baseline Pcv-aCO2 and ΔPcv-aCO2 to define fluid responsiveness was 0.85 (95%CI = 0.66-1.00) and 0.84 (95%CI = 0.63-1.00), respectively, and the positive predictive value was 1 when the cut-off value was 8.0 mmHg and -4.2 mmHg, respectively. 45.8% (11/24) patients responded to the fluid challenge in patients whose baseline Pcv-aCO2 ≤ 6 mmHg. There was no predictive value of baseline Pcv-aCO2 and ΔPcv-aCO2 on fluid responsiveness. Pcv-aCO2 and its change cannot serve as a surrogate of the change in cardiac output to define the response to fluid challenge in septic shock patients whose baseline Pcv-aCO2 ≤ 6 mmHg, while the predictive values of baseline Pcv-aCO2 and the change in Pcv-aCO2 are presented in patients with the initial value of Pcv-aCO2 > 6 mmHg. Clinical Trials, NCT01941472.

Response to fluid challenge is often defined as an increase in cardiac index (CI) of more than 10-15%. However, in clinical practice CI values are often not available. We evaluated whether changes in mean arterial pressure (MAP) correlate with changes in CI after fluid challenge in patients with septic shock. This was an observational study in which we reviewed prospectively collected data from 51 septic shock patients in whom complete hemodynamic measurements had been obtained before and after a fluid challenge with 1,000 ml crystalloid (Hartman's solution) or 500 ml colloid (hydroxyethyl starch 6%). CI was measured using thermodilution. Patients were divided into two groups (responders and non-responders) according to their change in CI (responders: %CI >10%) after the fluid challenge. Statistical analysis was performed using a two-way analysis of variance test followed by a Student's t test with adjustment for multiple comparisons. Pearson's correlation and receiver operating characteristic curve analysis were also used. Mean patient age was 67 ± 17 years and mean Sequential Organ Failure Assessment (SOFA) upon admittance to the intensive care unit was 10 ± 3. In the 25 responders, MAP increased from 69 ± 9 to 77 ± 9 mmHg, pulse pressure (PP) increased from 59 ± 15 to 67 ± 16, and CI increased from 2.8 ± 0.8 to 3.4 ± 0.9 L/min/m(2) (all p < 0.001). There were no significant correlations between the changes in MAP, PP, and CI. Changes in MAP do not reliably track changes in CI after fluid challenge in patients with septic shock and, consequently, should be interpreted carefully when evaluating the response to fluid challenge in such patients.

Fluid challenge test is a widely used method for the detection of fluid responsiveness in acute circulatory failure. However, detection of the patient's response to the fluid challenge requires monitoring of cardiac output which is not feasible in many settings. We investigated whether the changes in the pulse oximetry-derived peripheral perfusion index (PPI), as a non-invasive surrogate of cardiac output, can detect fluid responsiveness using the fluid challenge testor not. We prospectively enrolled 58 patients with septic shock on norepinephrine infusion. Fluid challenge test, using 200mL crystalloid solution, was performed in all study subjects. All patients received an additional 300mL crystalloid infusion to confirm fluid responsiveness. Velocity time integral (VTI) (using transthoracic echocardiography), and PPI were measured at the baseline, after 200mL fluid challenge, and after completion of 500mL crystalloids. Fluid responsiveness was defined by 10% increase in the VTI after completion of the 500mL. The predictive ability of ∆PPI [Calculated as (PPI after 200mL - baseline PPI)/baseline PPI] to detect fluid responders was obtained using the receiver operating characteristic curve. Forty-two patients (74%) were fluid responders; in whom, the mean arterial pressure, the central venous pressure, the VTI, and the PPI increased after fluid administration compared to the baseline values. ∆PPI showed moderate ability to detect fluid responders [area under receiver operating characteristic curve (95% confidence interval) 0.82 (0.70-0.91), sensitivity 76%, specificity 80%, positive predictive value 92%, negative predictive value 54%, cutoff value ≥ 5%]. There was a significant correlation between ∆PPI and ∆VTI induced by the fluid challenge. ∆PPI showed moderate ability to detect fluid responsiveness in patients with septic shock on norepinephrine infusion. Increased PPI after 200mL crystalloid challenge can detect fluid responsiveness with a positive predictive value of 92%; however, failure of the PPI to increase does not exclude fluid responsiveness. NCT03805321. Date of registration: 15 January 2019. Clinical trial registration URL: https://clinicaltrials.gov/ct2/show/NCT03805321?term=ahmed+hasanin&rank=9 .

Response

To explore the short-term hemodynamic change of fluid challenge (FC) with crystalloid or colloid and define fluid responsiveness at the optimal time in patients with septic shock. A prospective observational study was conducted. Septic shock patients monitored with pulmonary catheters admitted to medical intensive care unit (ICU) of the Peking Union Medical College Hospital from July 2016 to December 2018 were enrolled. All included patients received FC and were divided into two groups according to the type of fluid used, i.e. crystalloid group (normal saline for 500 mL) and colloid group (4% succinyl gelatin for 500 mL). The choice of fluid type was decided by the attending physician. Hemodynamic variables were measured at baseline, and 0 (immediately), 10, 30, 45, 60, 90, 120 minutes after FC, included cardiac index (CI), heart rate (HR), mean artery pressure (MAP), central venous pressure (CVP) and pulmonary arterial wedge pressure (PAWP). Fluid responsiveness was defined as CI increased by more than 10% after FC. The data were analyzed by repeated measurements of variance between the two groups as well as responders and nonresponders. Forty patients were included, 20 cases each in colloid group and crystalloid group; of whom 26 were fluid responders with 12 of colloid group and 14 of crystalloid group. Of the 14 nonresponders, 8 were of colloid group and 6 of crystalloid group. (1) Compared with before FC, CI (mL×s-1×m-2) was significantly increased in crystalloid and colloid groups after FC (71.7±16.7 vs. 65.0±16.7, 68.3±25.0 vs. 63.3±23.3, both P < 0.05). In the colloid group, volume expansion increased the CI to maximum (76.7±18.3) at 30 minutes after FC, at 120 minutes after FC, a significantly higher CI (70.0±16.7) was also observed (P < 0.05), an increased in CI ≥ 10% was observed at 60 minutes after FC. In the crystalloid group, CI was increased to maximum at 10 minutes (73.3±28.3) and decreased to baseline at 60 minutes, an increased in CI ≥ 10% was also observed at 10 minutes after FC. In addition, there was no significant difference in CI changes between colloidal group and crystalloid group at different time points after FC. (2) CI did not change over time in nonresponders groups, whereas in responders CI increased parallelly to that in both crystalloid and colloid groups over time. However, an increased in CI ≥ 10% was observed through the 120 minutes after FC in responders of colloid group compared with that of at 30 minutes after FC in crystalloid group. There was significant difference in CI changes between colloidal group and crystalloid group at 30, 45, 60, 90 minutes after FC (mL×s-1×m-2: 18.3±3.3 vs. 8.3±1.7, 18.3±3.3 vs. 5.0±1.7, 13.3±1.7 vs. 3.3±1.7, 11.7±3.3 vs. 3.3±1.7, all P < 0.05). (3) The maximal values of CVP and PAWP were observed at the end of FC. In colloid group, both the two variables were notably higher than that before FC over 120 minutes compared with that of only at 10 minutes in crystalloid group. The MAP in colloid increased to maximum immediately at the end of FC and decreased to baseline at 45 minutes, however, the MAP in crystalloid group and HR of both groups showed no differences over 120 minutes. Hemodynamic changes were significantly different between crystalloid and colloid after FC in patients with septic shock. Therefore, the timing of fluid responsiveness assessment should be different individually. The assessment time of colloid group may be prolonged to 30 minutes after FC while that of crystal group can be at 10 minute after FC.

Capillary refill time assessment after fluid challenge in patients on venoarterial extracorporeal membrane oxygenation: A retrospective study

Objective To evaluate whether the changes in the radial artery pulse pressure (rPP) can predict the changes in stroke volume (SV) after fluid challenge in patients after cardiac surgery. Methods This prospective observational study included 75 mechanical ventilated patients with hypotension after cardiac surgery, where all the patients involved underwent rPP and SV measurement after fluid challenges. Accordingly, the patients were divided into a volume responder group (increases in SV≥15%, n=45) and a non-responder group (increases in SV<15%, n=30). Then, heart rate (HR), blood pressure(BP), mean arterial pressure (MAP), central venous pressure (CVP), SV and stroke volume variation (SVV) were collected at baseline level and after fluid challenges respectively. The ability of the indices to predict fluid responsiveness, the area under the receiver operating characteristic curve (AUC), sensitivity and specificity for predicting fluid responsiveness were calculated. Results In the study, 60% of the patients were defined as fluid responders. BP, MAP, CVP, SV increased significantly in the volume responder group(P<0.05), while HR and SVV tended to decrease. Increases in rPP induced by fluid challenges (≥13%) indicated SV increases (≥15%) with a sensitivity of 0.82 and a specificity of 0.83. The AUC was 0.90 [95% confidence interval(CI) 0.81-0.96]. Conclusions The changes in rPP induced by fluid challenges can be used to predict the changes in SV in patients after cardiac surgery. Key words: Fluid responsiveness; Radial artery; Pulse pressure; Stroke volume; Fluid challenge; Cardiac surgery

Background:Capillary refill time (CRT) is the gold standard for evaluating peripheral organ perfusion; however, intraoperative CRT measurement is rarely used because it cannot be conducted continuously, and it is difficult to perform during general anesthesia. The peripheral perfusion index (PI) is another noninvasive method for evaluating peripheral perfusion. The PI can easily and continuously evaluate peripheral perfusion and could be an alternative to CRT for use during general anesthesia. This study aimed to determine the cutoff PI value for low peripheral perfusion status (prolonged CRT) by exploring the relationship between CRT and the PI during general anesthesia.Methods:We enrolled 127 surgical patients. CRT and the PI were measured in a hemodynamically stable state during general anesthesia. A CRT >3 s indicated a low perfusion status.Results:Prolonged CRT was observed in 27 patients. The median PI values in the non-prolonged and prolonged CRT groups were 5.0 (3.3–7.9) and 1.5 (1.2–1.9), respectively. There was a strong negative correlation between the PI and CRT (r = −0.706). The area under the receiver operating characteristic curve generated for the PI was 0.989 (95% confidence interval, 0.976–1.0). The cutoff PI value for detecting a prolonged CRT was 1.8.Conclusion:A PI <1.8 could accurately predict a low perfusion status during general anesthesia in the operating room. A PI <1.8 could be used to alert the possibility of a low perfusion status in the operating room.Trial Registration:University Hospital Medical Information Network (UMIN000043707; retrospectively registered on March 22, 2021, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno = R000049905).

Introduction: The high mortality rate and organ dysfunction in septic shock indicate the need for early intervention and research on septic shock patients. Therefore, the study of peripheral perfusion index (PPI) and capillary refill time (CRT) is expected to be used as a reference for assessing fluid responsiveness in septic shock patients in the Intensive Care Unit (ICU). The study aimed to discuss peripheral perfusion index (PPI) and capillary refill time (CRT) for assessing fluid responsiveness in septic shock patients in the Intensive Care Unit (ICU). Design: The study design was an analytical cross-sectional study, conducted from from May 1st, 2022 to September 1st, 2022. All patients with clinical sepsis and septic shock were admitted to the ICU ward and served as population of the study. The intervention given was a mini fluid challenge with a dose of 4 ml/kgBW is administered over 15 minutes. The PPI and CRT variables will be grouped based on fluid response, and diagnostic test analysis will be conducted by assessing sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. Results: The validity of the PPI examination based on mean arterial pressure (MAP) in detecting fluid responsiveness yielded a sensitivity of 66.6%, a specificity of 31.6%, a negative predictive value of 94.7%, a positive predictive value of 4.87%, and an accuracy of 33.3%. The validity of the CRT examination in detecting fluid responsiveness showed a sensitivity of 33.3%, a specificity of 75.4%, a negative predictive value of 95.5%, a positive predictive value of 6.66%, and an accuracy of 73.3%, and it varies in the analysis based on heart rate, ΔpCO2, and lactate values. Conclusions: In detecting fluid responsiveness in sepsis and septic shock patients, the PPI has better sensitivity, while CRT exhibits better specificity.

Peripheral perfusion in critically ill patients frequently is assessed by use of clinical signs. Recently, the pulse oximetry signal has been suggested to reflect changes in peripheral perfusion. A peripheral perfusion index based on analysis of the pulse oximetry signal has been implemented in monitoring systems as an index of peripheral perfusion. No data on the variation of this index in the normal population are available, and clinical application of this variable in critically ill patients has not been reported. We therefore studied the variation of the peripheral perfusion index in healthy adults and related it to the central-to-toe temperature difference and capillary refill time in critically ill patients after changes in clinical signs of peripheral perfusion. Prospective study. University-affiliated teaching hospital. One hundred eight healthy adult volunteers and 37 adult critically ill patients. None. Capillary refill time, peripheral perfusion index, and arterial oxygen saturation were measured in healthy adults (group 1). Capillary refill time, peripheral perfusion index, arterial oxygen saturation, central-to-toe temperature difference, and hemodynamic variables were measured in critically ill patients (group 2) during different peripheral perfusion profiles. Poor peripheral perfusion was defined as a capillary refill time >2 secs and central-to-toe temperature difference > or = 7 degrees C. Peripheral perfusion index and arterial oxygen saturation were measured by using the Philips Medical Systems Viridia/56S monitor. In group 1, measurements were made before and after a meal. In group 2, two measurements were made, with the second measurement taken when the peripheral perfusion profile had changed. A total of 216 measurements were carried out in group 1. The distribution of the peripheral perfusion index was skewed and values ranged from 0.3 to 10.0, median 1.4 (inner quartile range, 0.7-3.0). Seventy-four measurements were carried out in group 2. A significant correlation between the peripheral perfusion index and the core-to-toe temperature difference was found (R2=.52; p <.001). A cutoff peripheral perfusion index value of 1.4 (calculated by constructing a receiver operating characteristic curve) best reflected the presence of poor peripheral perfusion in critically ill patients. Changes in peripheral perfusion index and changes in core-to-toe temperature difference correlated significantly (R =.52, p <.001). The peripheral perfusion index distribution in the normal population is highly skewed. Changes in the peripheral perfusion index reflect changes in the core-to-toe temperature difference. Therefore, peripheral perfusion index measurements can be used to monitor peripheral perfusion in critically ill patients.

Optimizing fluid management for operation has become a topic of increasing interest. The static parameters of cardiac preload, such as central venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP) are poor predictors of fluid responsiveness (FR) [1], and it is not appropriate to use these parameters for making decisions regarding fluid management. Two reasons can be given for this, considering the FrankStarling relationship. Firstly, markers of preload are not always accurate measures of cardiac preload. Secondly, assessment of preload is not assessment of preload responsiveness [2]. Alternatives for detecting FR have been investigated and the concept of respiratory variations of hemodynamic signals has emerged based on heart-lung interactions during mechanical ventilation [3]. Many dynamic parameters such as systolic pressure variability, pulse pressure variability (PPV) and stroke volume variability (SVV) from pulse-contour analysis have been shown to be predictive of FR [4]. These variables are highly accurate for FR and have a greater accuracy than the traditional static indices [5]. Recently, the noninvasive pulse oximeter-derived pleth variability index (PVI) was introduced. This index predicts FR as accurately as do SVV and PVI-based goal-directed fluid management reduced intraoperative and postoperative lactate levels [6]. However, these dynamic parameters cannot be used in patients who have spontaneous ventilation or cardiac arrhythmia. A low tidal volume also makes these variables poorly predictable [7]. The chest must be closed and intra abdominal pressure has to be within the normal range [8,9]. SVV is influenced by positive end-expiratory pressure and ventricular function. Likewise, the changes of vasomotor tone impact the plethysmographic waveform [10]. Researchers have thus sought alternative predictors of FR for use in patients with spontaneous breathing. The passive leg-raising (PLR) test was developed and is considered to be the gold-standard method for this group and can also be used in mechanically ventilated patients. Elevation of the patients’ legs to 45˚ autotransfuses around 300 ml of whole blood into the central circulation. Many studies show an increase in PAOP, left ventricular end-diastolic dimension, E-wave of mitral flow, and left ventricular ejection time during PLR [11]. Kweon et al. [12] in the current issue of the Korean Journal of Anesthesiology, compared the hemodynamic changes of PLR and exaggerated lithotomy position. They showed an increase in mean blood pressure, PAOP, CVP, the left ventricular enddiastolic area index, and systemic vascular resistance in both positions, but there was an increase of cardiac output in PLR only. Although FR is not the main subject of this article, it may be helpful to understand the hemodynamic response of fluid challenge in patients under general anesthesia. PLR has been validated for predicting FR, but it requires the determination of cardiac output with a fast-response device, because the hemodynamic changes may be transient. Available techniques are transthoracic echocardiography, transpulmonary thermodilution, transthoracic Doppler ultrasonography, and stroke volume from analysis of the systemic arterial pressure wave [13]. Although they have many limitations, dynamic parameters have the potential to help anesthesiologists in making decision about fluid therapy in patients under general anesthesia with mechanical ventilation. The PLR test may be helpful for the evaluation of the volume status of patients preoperatively, especially in an emergency operation in which there is not enough time to evaluate and correct volume status. There are many studies that show dynamic parameters and PLR test

BackgroundThe relationship between fluid responsiveness and right-and left-sided congestion remains underexplored. This study aimed to delineate the dynamic behaviour of venous congestion and extravascular lung water index (EVLWI) during a fluid challenge depending on the concomitant changes in cardiac index (CI).MethodsIn patients from three intensive care units, for whom a 500-mL fluid challenge was administered, we retrospectively analysed CI, central venous pressure (CVP), venous excess ultrasound (VExUS), and EVLWI, which had been prospectively recorded. A VExUS congestion point was calculated from 0 to 7 by assigning 1 point to each degree of abnormality for the 4 investigated veins. A subgroup analysis was planned in patients with acute respiratory distress syndrome (ARDS).ResultsWe analysed 64 patients, of whom 42 (66%) were fluid responders (FR+) defined by a CI increase ≥ 15% with fluid infusion. Before the fluid challenge, CVP was lower in FR + than in fluid non-responders (FR-) (7.3 [2.9–10.3] vs. 10.6 [8.2–13.0] mmHg,respectively, p = 0.002). VExUS grades and congestion points were not different between FR + and FR- (Grade 0: 62% vs. 55%, respectively, p = 0.601; congestion points: 1.0 [0.0–2.3] vs. 2.0 [1.0–3.0], respectively, p = 0.053). EVLWI was also similar between groups. Following fluid administration, VExUS grade deterioration occurred in 5% of FR + versus 73% of FR− (p < 0.001). After the fluid challenge, abnormal VExUS grades were more prevalent in FR − than in FR+ (91% vs. 43%, respectively, p < 0.001), and congestion points were higher (4.0 [3.0–5.0] vs. 1.5 [1.0–3.0], respectively, p < 0.001). CVP increased by 1.4 [0.4–2.4] mmHg in FR + and 2.0 [1.1–3.5] mmHg in FR- (p = 0.064). Among 25 patients with ARDS, EVLWI increased more than in patients without ARDS, in both FR- (by 1.7 [0.9–3.3] vs. 0.7 [0–1.4] mL/kg, respectively, p = 0.046) and FR+ (by 1.0 [-0.6–2.5] vs. 0 [-0.7–0.4] mL/kg, respectively, p = 0.009).ConclusionA fluid challenge worsened venous congestion, assessed by VExUS as well as CVP, in fluid non-responders, while it was not in fluid responders.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1186/s13054-025-05803-y.

Arterial blood pressure is the most common variable used to assess the response to a fluid challenge in routine clinical practice. The aim of this study was to evaluate the accuracy of the change in the radial artery pulse pressure (rPP) to detect the change in cardiac output after a fluid challenge in patients with septic shock. Prospective observational study including 35 patients with septic shock in which rPP and cardiac output were measured before and after a fluid challenge with 400 mL of crystalloid solution. Cardiac output was measured with intermittent thermodilution technique using a pulmonary artery catheter. Patients were divided between responders (increase >15% of cardiac output after fluid challenge) and nonresponders. The area under the receiver operating characteristic curve (AUROC), Pearson correlation coefficient and paired Student t test were used in statistical analysis. Forty-three percent of the patients were fluid responders. The change in rPP could not neither discriminate between responders and nonresponders (AUROC = 0.52; [95% confidence interval: 0.31-0.72] P = .8) nor correlate (r = .21, P = .1) with the change in cardiac output after the fluid challenge. The change in rPP neither discriminated between fluid responders and nonresponders nor correlated with the change in cardiac output after a fluid challenge. The change in rPP cannot serve as a surrogate of the change in cardiac output to assess the response to a fluid challenge in patients with septic shock.

Invasive and noninvasive cardiovascular monitoring options for cardiac surgery

Comparison of the diagnostic accuracy of dynamic and static preload indexes to predict fluid responsiveness in mechanically ventilated, isoflurane anesthetized dogs