|Year : 2022 | Volume
| Issue : 4 | Page : 330-336
Changes in carotid corrected flow time in guiding fluid resuscitation in septic patients
Sherif Sabri1, Ahmed Abdelbasset2, Ahmed Yassien1, Ahmed Nashaat1
1 Department of Critical Care, Beni Suef University Hospital, Egypt
2 Department ofRadiology, Beni Suef University Hospital, Beni Suef, Egypt
|Date of Submission||01-Sep-2021|
|Date of Acceptance||01-Oct-2022|
|Date of Web Publication||29-Dec-2022|
MD Ahmed Abdelbasset
Department of Radiology, Beni Sueif Zip Code: 62511
Source of Support: None, Conflict of Interest: None
Introduction Accurate estimation of intravascular volume status is important in the resuscitation of patients in ICUs. Although intensive fluid therapy in patients with life-threatening volume depletion can prevent death and end-organ damage, volume overload is known to result in increased mortality, morbidity, and duration of hospital stay. Ultrasonography has become a common diagnostic choice in assessment of fluid status in septic patients. This method is noninvasive, easy to learn, and provides real-time assessment at the patient’s bedside. Various ultrasound modalities have been developed to provide accurate and minimally invasive assessment of volume status. In this regard, one of the most promising methods is the evaluation of the blood flow velocity waveform in the descending thoracic aorta via a nonimaging Doppler probe. This modality is based on calculating the systolic flow time with cycle time correction [corrected flow time (FTc)]. FTc is known to be directly associated with volume status. FTc measurement in carotid artery is a completely noninvasive and much more feasible approach.
Aim To compare the use of ultrasonography in the measurement of the changes in carotid FTc with echocardiography in the assessment of changes in heart dynamics to assess changes in volume status before and after passive leg raising (PLR) in septic patients.
Patients and methods A total of 40 septic patients, including 18 (45.5%) patients as fluid responders and 22 (54.5%) patients as nonfluid responders, were included. Increased FTc by 7 ms, as well as 10% increase in stroke volume was considered to be fluid responsive.
Results Our study results showed that 45.5% (n=18) of study population were fluid responders. The PLR test could assess fluid responsiveness with a specificity of 100% and sensitivity of 95% at a cutoff of 10.6% change in CO to predict fluid responsiveness. The study showed a statistically significant moderate positive correlation between CCA FTc and the percent of change in CO measured by echocardiography. An agreement analysis was formed. We concluded that there was a strong relation between change in carotid corrected blood flow and change in COP before and after PLR, with P value less than 0.001. Therefore, we can use this parameter to predict fluid responsiveness after PLR.
Conclusions Carotid artery blood flow is a promising noninvasive and easy-to-perform tool for the evaluation of fluid responsiveness in critically ill septic patients. The PLR maneuver has demonstrated excellent performance for predicting fluid responsiveness. It is simple to perform but requires a reliable system of carotid corrected blood flow (COP) monitoring able to quantify the short-term changes.
Keywords: corrected flow time, COP monitoring, passive leg raise, ultrasonography
|How to cite this article:|
Sabri S, Abdelbasset A, Yassien A, Nashaat A. Changes in carotid corrected flow time in guiding fluid resuscitation in septic patients. Res Opin Anesth Intensive Care 2022;9:330-6
|How to cite this URL:|
Sabri S, Abdelbasset A, Yassien A, Nashaat A. Changes in carotid corrected flow time in guiding fluid resuscitation in septic patients. Res Opin Anesth Intensive Care [serial online] 2022 [cited 2023 Mar 26];9:330-6. Available from: http://www.roaic.eg.net/text.asp?2022/9/4/330/365798
| Introduction|| |
There has been an ever-growing interest in point-of-care ultrasonography owing to its potential to provide repeated real-time assessment of the same measure at bedside, which is noninvasive and easy to learn. Several noninvasive modalities to assess volume status via ultrasonography have been introduced . One of the most accepted modalities is the measurement of corrected flow time (FTc) in thoracic aorta via a nonimaging esophageal Doppler probe having proven to be a reliable predictor of volume status in several studies . FTc is calculated by measuring systolic flow time with the correction of heart rate (flow time/√cycle time, Bazett’s formula)  and is known to be proportional to preload and cardiac inotropy as the indices of volume status and cardiac function, respectively ,. Even though the measurement of thoracic aorta FTc is limited owing to technical difficulties and the need for expert operators, Annane et al.  showed that FTc can be measured in carotid artery with ease and reliability. Moreover, changes in carotid FTc are correlated with both increase  and decrease , in intravascular volumes. It has recently been shown that there is a direct and significant correlation between FTc in carotid artery and the loss of intravascular volume in a hemodialysis model of volume removal . However, as the measurement of FTc in carotid artery via ultrasonography is a new concept, there is a need to define its normal values. This could contribute to the accurate interpretation of the measurement and facilitate further efforts to define cutoff points needed for the assessment of the diagnostic accuracy of this ultrasound modality. Understanding of these normal values could also make possible the implantation of this new modality in the clinical setting. Hence, as the primary outcome, the current study aimed to investigate the normal ranges of FTc and its probable influential factors in healthy adult volunteers. Moreover, as it has been shown that passive leg raise (PLR) with the patient in supine position increases venous return and preload by about 150 ml , we measured pre-PLR and post-PLR FTc to investigate, as a secondary outcome, if such small amounts of change in intravascular volume are detectable by FTc.
| Aim|| |
The aim was to use carotid ultrasonography to detect changes in carotid FTc in comparison with echocardiography in the assessment of changes in heart dynamics to assess changes in volume status before and after PLR in septic patients.
| Patients and methods|| |
This is a clinical randomized observational study that was conducted on 40 patients diagnosed as having sepsis and septic shock. Patients were admitted to the Critical Care Department in Beni-Suef University Hospital during the period from August 2018 till November 2019. The study was approved by the ethical committee of faculty of medicine Beni-Suef University.
Inclusion criteria: sepsis is defined as patient who had two or more of the qSOFA score:
- Respiratory rate more than 22 breath/min.
- Altered mentation.
- Systolic blood pressure less than 100 mmHg.
Septic shock is defined as sepsis with persisting hypotension requiring vasopressor to maintain mean arterial pressure (MAP) less than 65 mmHg and having a serum lactate level less than 2 mmol/l despite adequate resuscitation .
Exclusion criteris were as follows:
- Patients less than 18 years old.
- Patients with neurogenic shock, obstructive shock, and cardiogenic shock.
- Any abnormality in carotid artery (carotid stenosis, aneurysm, or kinking).
- Patients on sedation.
Contraindications to PLR were as follows :
- Head trauma.
- Venous compression stockings.
- Conditions that raise intra-abdominal pressure.
All 40 patients included in our thesis were subjected to the standard study protocol consisting of the following.
Carotid corrected flow time before and after passive leg raising
Uncorrected flow time was measured in a representative beat by measuring the time from the start of systolic upstroke to the start of the dicrotic notch and recorded in milliseconds. However, cycle time was rom beginning of the current beat to the beginning of the adjacent beat and recorded in seconds. Flow time was then corrected for heart rate using the following formula :
Corrected flow time=flow time/√cycle time
Measurement of stroke volume and cardiac output before and after passive leg raising
LVOT diameter was measured in this parasternal long axis in biplane mode at mid-systolic 1 cm below the aortic valve.
Then, LVOT was measured by using pulsed wave-Doppler at the base of the aortic leaflets, and then moving slowly away toward the LVOT until a typical subvalvular flow profile was (∼1 cm below the aortic valve) obtained. A full-volume recording of LV during four cardiac cycles was performed .
SV and COP were measured from VTI and LVOT using following equation:
Passive leg raising
The patient placed at 45° with head-up in a semirecumbent position lower patient’s upper body to horizontal and passively raises legs at 45° up maximal effect occurs at 30–90 s.
- 10% increase in stroke volume was considered to be fluid responsive.
- Increase in FTc by 7 mswas considered to be fluid responsive.
| Results|| |
As summarized in [Table 1], baseline characteristics such as age, sex, comorbidities and risk factors, APACHE II score, respiratory rate, heart rate, or arterial blood gas were not significantly different between both groups (all P<0.05). However, Central venous pressure (CVP) and MAP were significantly different between both groups (P>0.05) ([Table 2]).
|Table 1 Baseline characteristics of age, gender, co-morbidities and risk factors, APACHE II score, respiratory rate, Heart rate or ABG between both groups|
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|Table 2 Comparing between two study groups regarding SV and SV% by analysis of variance|
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There was a statistically significant difference between responders and nonresponders regarding COP and COP% in the study group by analysis of variance (ANOVA) test (P<0.05) ([Table 3]).
|Table 3 Comparing between study groups regarding COP and raising COP after passive leg raise by analysis of variance test in the study group|
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There was a statistically significant difference between responders and nonresponders regarding FTC and change in FTC after PLR in comparison with before FTC ([Table 4]).
|Table 4 Comparing between study groups regarding carotid flow time and increase in carotid flow time after leg raising by ANOVA test in the study group|
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Pearson correlation between % CVP and % Echo COP.
There was a statistically significant positive linear correlation between % CVP and % Echo COP after PLR (r 0.537), with P value less than 0.0001 by ANOVA test (P<0.05).
Pearson correlation between % MAP and % Echo COP.
There was a statistically significant positive linear correlation between % MAP and % echo COP after PLR, with r=0.537 and P value less than 0.0001 by ANOVA test (P <0.05).
Pearson correlation of carotid FTc and changes of COP
There was a statistically insignificant correlation between FTC% and change COP% after PLR, with r=0.537 and P value less than 0.0001.
| Discussion|| |
Accurate assessment of intravascular fluid status and measurement of fluid responsiveness have become increasingly important in critical care. It is now widely recognized that both inadequate and excessive fluid replacement are deleterious to health, and both can affect recovery during critical illness. Clinical studies have consistently demonstrated that only about 50% of hemodynamically unstable patients are volume responsive. It is therefore essential to have reliable bedside tools to predict the efficacy of volume expansion and thus distinguishing patients who might benefit from volume expansion from those in whom the treatment is likely to be inefficacious .
This was a prospective observational study conducted on 50 critically ill septic patients admitted to Critical Care Department of Beni Suef University Hospital. The aim of this study was to investigate the accuracy of carotid artery flow time measurement in the assessment of fluid responsiveness in critically ill septic patients. We also aimed to investigate the accuracy of PLR maneuver as a simple easy method in hemodynamic evaluation of critically ill septic patients.
Regarding hemodynamic data (SBP, DBP, MAP, and heart rate), this study demonstrated a statistically significant difference between responders and nonresponders regarding % MAP, which showed a moderate correlation with % CO (r=0.543 and P=0.0028) that was used to evaluate fluid responsiveness.
The findings were in agreement with Marik et al.  and Malbrain et al.. The previous studies found a statistically significant correlation between MAP and %PP and percentage cardiac output (%CO) after fluid challenge but with variable degrees of correlation strength (r=0.34, 0.52, P=0.001 and r=0.56, P=0.001, respectively).
In line with our results, Malbrain et al.  and Marik et al.  showed that noninvasive measurements of BP did not show worse performance than invasive measurements, even in case of arrhythmia. In contrary to our results, Thiel et al.  found that noninvasive blood pressure monitoring was not sensitive or specific predictor of fluid responsiveness in healthy volunteers.
In contrast to our results, Pierrakos et al.  showed a lack of correlation between changes in arterial pressure and CI after fluid challenge in patients with septic shock, but there was an agreement regarding increasing of MAP after fluid challenge in responders. This could be explained by the different variables used to assess fluid responsiveness, which was cardiac index measured by PAC versus echocardiography, and the heterogeneity of study population, as we included both sepsis and septic shock patients
Our study showed statistically significant difference in CVP after PLR and FC, being higher in the responder group. This was in line with Le Manach et al.  and Pierrakos et al. .
Our results showed a weak correlation between baseline CVP and % COP (r=−0.297, −0.291). This was in agreement with a meta-analysis published by Marik and Cavallazzi . They found a correlation coefficient between the baseline CVP and the delta SVI/CI (r=0.18; 95% CI, 0.1–0.25), being 0.28 (95% CI, 0.16–0.40) in the ICU patients and 0.11 (95% CI, 0.02–0.21) in the operating room patients. Keeping in mind the results of this meta-analysis, CVP by itself is not a good predictor of preload responsiveness.
In contrary with our results, Thiel et al.  found that the initial CVP was not different between the groups of responders and nonresponders, and the change in CVP did not correlate with the change in SV following volume expansion. In the view of this controversy, Surviving Sepsis Campaign 2016  stated that no harm was associated with the interventional strategies; thus, the use of the previous targets (CVP) is still safe and may be considered despite of its limited usefulness within normal range to predict fluid responsiveness. The use of CVP alone to guide fluid resuscitation can no longer be justified because the ability to predict response to a fluid challenge when the CVP is within a relatively normal range (8–12 mmHg) is limited . Moreover, in a recent observational study conducted in ICUs around the world, CVP has been reported as the most frequently used parameter to guide fluid administration.
In echocardiography result discussion, our study results showed that 75.5% (n=20) of the study population were fluid responders with use of 15% change in COP. This result strengthens the concept that about 65% only of septic patients are fluid responder.
In agreement with our study, Thiel et al.  found that 66% of their studied patients were fluid responders with great similarity of the studied population.
This was in concordance with a meta-analysis done by Chaves et al. . They concluded that ∼58% of spontaneously breathing patients were fluid responsive. The studies used different parameters and values to predict fluid responsiveness, including SV, COP, CI, and VTI and from 10 to 15% cutoff value to define fluid responsiveness in different hospital settings, for example, ICU, ED, and OR.
This finding reinforces the importance of assessing fluid responsiveness in critically ill patients before intravascular volume expansion, thus avoiding unnecessary exposure to additional fluids.
Echocardiographic measures such as SV and IVC represent important tools to assess fluid responsiveness in patients without availability of an invasive arterial line. Although it is operator dependent, echocardiography is a noninvasive technique that enables fluid responsiveness assessment with good accuracy in spontaneously breathing patients . The main disadvantages of echocardiographic measurements are non-continuous monitoring and high interrater variability.
The study found that PLR test could assess fluid responsiveness with specificity 100% and sensitivity 95% at a cutoff of 10% change in COP to predict fluid responsiveness.
Our results are consistent with results of the two meta-analyses by Monnet et al.  and Cherpanath et al. . Both reviewed the existing literature, in which the ability of the PLR maneuver to predict a significant increase in CO was tested. The pooled sensitivity and specificity in more than 20 studies, comprising 1000 patients, included in the analysis were 0.85–0.86 and 0.91–0.92, respectively, with an AUROC of 0.95. When seeking for the best threshold of PLR-induced changes in CO for predicting fluid responsiveness, the proposed value was 10%.
Importantly, the diagnostic performance was also maintained independently from the patients being spontaneously breathing or under controlled mechanical ventilation .
In common carotid data discussion, our study results showed that there was a statistically significant difference between responders and nonresponders regarding carotid artery FTc both after PLR. We also found a significant correlation between % cFT and %COP, indicating the ability to use this measures as a surrogate of echocardiography in assessment of fluid responsiveness, being noninvasive, repeatable, and the structures of interest are superficial in location, thus easy to image.
Our study results demonstrated that fluid responsiveness in critically ill septic patients could be efficiently predicted by %cFT with good sensitivity (90–95%) and specificity (100%) when compared with PLR test on cardiac parameters measured by echocardiography.
Our results were in agreement with Ma et al. . They found that carotid flow time measurements correlated moderately with cardiac output regardless of the use of a single waveform or an average of three waveforms (ρ=0.44, 95% CI 0.18–0.63, P=0.004, and ρ=0.41, 95% CI 0.16, P=0.004, respectively).
In concordance with our study, Gassner et al.  showed almost perfect correlation between FTc measurement and the CO measured by invasive pulmonary artery (PA) catheter or arterial waveform pulse contour analysis (PCA). The studied patients were diverse medical and surgical cases, with different diagnoses admitted to ICU.
In addition, Marik and Cavallazzi  suggested that changes in corrected carotid flow following a PLR maneuver may be a useful adjunctive method for determining fluid responsiveness in mixed spontaneous and mechanically ventilated patients. They found a strong correlation between the percent change in SVI by PLR measured by Bioreactance and the concomitant percent change in corrected carotid flow (r=0.59, P=0.0003). Using an increase in corrected carotid flow of 7% for predicting volume responsiveness, they found two false positive results and one false negative result, giving a sensitivity and specificity of 94 and 86%, respectively
The difference in sensitivity and specificity between the study by Marik and colleagues and our study could be explained by the different methods used to define fluid responsiveness. We used echocardiography as a gold standard, whereas in their study, bioreactance was used. It uses the frequency modulation of transthoracic voltage and depends on calculated algorithms, which is a limitation for its use.
Moreover, Roehrig et al.  found a significant correlation between changes in CCA Doppler flow ‘CCADflow’ and COP by thermodilution in postcardiac surgery patients following PLR (r=0.79; 0.60–0.891, P=0.0001, r2=0.63). This correlation did not change when only patients on SIMV or PSV were analyzed (r=0.78; 0.58–0.88, P<0.0001, r2=0.61). However, AUROC of CCAD flow was 0.54 (0.32–0.76) (P=0.74), which could not discriminate fluid responders.
The correlation overall was similar for corresponding changes carotid flow time and CO when analyzed before and after PLR compared with absolute values. Furthermore, equivalent correlations in patients with a volume-controlled mode of ventilation compared with patients on a pressure support mode suggest that intrathoracic pressure changes did not confound the carotid flow time/CO correlation, as proper active inspiratory efforts were absent during all measurements and PEEP and tidal volumes were comparable . Moreover, this results could be in line with our study results regarding whether the patients were spontaneously breathing or mechanically ventilated.
However, in contrast to our results, they could not discriminate fluid responders. This could be explained by the different patient populations as their study was conducted on postoperative cardiac surgery cases, which have altered pathophysiologic parameters after surgery.
The less-invasive methods are being used more often at the bedside to assess the patient’s hemodynamics and avoid inherited risk complications, and some limitations associated with the invasive methods. With appropriate patient selection, carotid blood flow measurement offers great promise as an accurate, easily accessible, and no-risk means of measuring CO in the critically ill population. The carotid ultrasound examination could be used in several settings, specifically when the inferior vena cava ultrasound method is not feasible because of poor acoustic windows. Theoretically, this new method should be less affected by confounding variables such as thorax and intra-abdominal pressure. However, the volemic status and fluid responsiveness are probably better assessed by the multimodal sonographic approach with other ultrasound methods such as inferior vena cava, carotid, cardiac and pulmonary ultrasound .
Carotid ultrasound must, of course, be placed in clinical context. It is generally accepted that dynamic methods are preferred measures of fluid responsiveness, but a single ideal test remains elusive. It is foreseeable that in the future, clinicians will determine fluid responsiveness with not a single test but instead a comprehensive set of measurements and clinical assessments, which may include carotid ultrasound .
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[Table 1], [Table 2], [Table 3], [Table 4]