Critical care ultrasound-guided fluid resuscitation versus early goal-directed therapy in patients with septic shock: A systematic review and Meta-analysis

doi:10.21203/rs.3.rs-1711004/v1

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Critical care ultrasound-guided fluid resuscitation versus early goal-directed therapy in patients with septic shock: A systematic review and Meta-analysis

https://doi.org/10.21203/rs.3.rs-1711004/v1

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published 08 May, 2023

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Background: Fluid resuscitation is a vital therapy for patients with septic shock. With the widespread application of ultrasound in critical care medicine, it is also used in the fluid resuscitation of critical patients. However, the effect of critical care ultrasound-guided fluid resuscitation (CCUGFR) in patients with septic shock needs further research.

Methods: We searched PubMed, Embase, Cochrane library, Web of Science, and Registers for randomized controlled trials from inception to April 2022, evaluating the prognosis of CCUGFR in patients with septic shock. Data were pooled by risk ratio (RR) or mean difference (MD) with their 95% confidence interval (CI) and estimated using fixed-effects or random-effects models.

Results: Twelve randomized controlled studies with a total of 947 participants were included, of which 473 used CCUGFR. CCUGFR in patients with septic shock was associated with reduced mortality (RR 0.78; 95%CI, 0.65, 0.94; P=0.007), with low heterogeneity (I²=0%, P=0.45), and 24-hour fluid volume (MD -1.02; 95%CI, -1.28, -0.75; P<0.001), with low heterogeneity (I²=0%, P=1.00). Increased norepinephrine dose (MD 0.07; 95%CI, 0.02, 0.11; P=0.002), with low heterogeneity (I²=45%, P=0.18), and dobutamine dose (MD 2.2; 95%CI, 0.35, 4.04; P=0.02), with low heterogeneity (I²=0%, P=0.61). There was no reduction in the risk of dobutamine users (RR 1.67; 95%CI, 0.52, 5.36; P=0.39), with low heterogeneity (I²=0%, P=0.86), and no difference in duration of vasopressin infusion (MD -5.46; 95%CI, -38.78, 27.86; P=0.75), with high heterogeneity (I²=97%, P<0.001). But taking left ventricular outflow tract velocity time integral (LVOT-VTI), passive leg raising test, inferior vena cava (IVC) related measures, or only IVC-related measures to evaluate fluid responsiveness was advantageous in the duration of vasopressin infusion. Subgroup analyses showed IVC-related measures and using passive leg raising test combined with echocardiography to assess fluid reactivity reduced hospital stay (MD -2.91; 95%CI, -5.2, -0.62; P=0.01) with low heterogeneity (I²=8%, P=0.34) and ICU length of stay (MD -2.77; 95%CI, -4.51, -1.02; P=0.002), with low heterogeneity (I²=0%, P=0.57).

Conclusion: Our findings suggested that in patients with septic shock receiving CCUGFR is beneficial. CCUGFR and fluid responsiveness using LVOT-VTI, passive leg raising test, and IVC-related measures may be preferable.

Trial registration: PROSPERO, CRD42022326566, Registered 10 May 2022

septic shock

ultrasonography

fluid therapy

resuscitation

mortality

meta-analysis

systematic review

Sepsis is a dysfunctional state of the host caused by a dysregulated reaction to the infection [1]. Severe sepsis and septic shock have attracted extensive attention due to high morbidity and mortality—the current estimates of 30 million episodes and 6 million deaths per year [2]. Therapy of severe sepsis and septic shock is complex and challenging. However, a deeper understanding of pathogenesis and treatment for septic shock has been gained with scholars' in-depth research on severe sepsis. In 2003, critical care and infectious diseases professors developed management guidelines for severe sepsis and septic shock to improve outcome [3].

Fluid resuscitation is one of the most basic treatments for septic shock. According to the Surviving Sepsis Guideline (SSC) in 2004, early goal-directed therapy (EGDT) was proposed to be administered within the first 6 hours after the septic shock is identified [3]. EGDT is a means of improving tissue perfusion by observing hemodynamic parameters along with responses to fluid resuscitation and vasopressor medications [4]. Nevertheless, some studies indicated that EGDT did not improve outcome [5, 6]. More and more studies have found that early administration of large amounts of crystalloids does not improve prognosis because of complications, and restrictive fluid resuscitation has reduced the use of vasoactive drugs and mechanical ventilation [7–9]. The 2021 SSC guidelines recommended that at least 30 mL/kg of crystalloid should be given intravenously within 3 hours of initial resuscitation. The use of non-invasive tools to assess the hemodynamic status, including echocardiography, was also recommended [10]. However, controversy still exists over whether ultrasonography is accurate and effective as the indicator for monitoring [11].

Ultrasound has been used in critical care medicine for more than 30 years due to its simple operation, non-invasiveness, and sustainable monitoring [12]. In recent years, critical care ultrasound technology has rapidly developed and applied in intensive care unit (ICU), forming ultrasound-guided interventional radiology, hemodynamic monitoring, and organ perfusion assessment [13–17]. Of course, critical care ultrasound has also been used to guide fluid resuscitation in patients with septic shock, such as lung ultrasound B-line scores to guide fluid management in patients with extravascular pulmonary water [18]. Patient's cardiac function and fluid responsiveness can be assessed by monitoring the size of the cardiac structure, the left ventricular ejection fraction, and left ventricular outflow tract velocity time integral (LVOT-VTI) [14, 19, 20]. Furthermore, fluid responsiveness can be more accurately assessed by inferior vena cava (IVC) diameter and degree of morphological variability [21].

So far, there is no consistent conclusion about the initial fluid resuscitation guided by critical care ultrasound in patients with septic shock because the results of clinical studies were controversial. To obtain reliable evidence, we conducted a systematic review and meta-analysis to compare critical care ultrasound guidance with early goal-directed therapy in patients with septic shock.

This systematic review and meta-analysis was registered on PROSPERO (CRD42022326566) and conducted following the PRISMA guidelines [22].

Search strategy

We searched PubMed, Embase, Cochrane Library, and Web of Science databases from the establishment to April 16, 2022, without restriction on language, country, or region. We also searched the Cochrane Central Register of Controlled Trials and the Chinese Clinical Trials Registry. The following terms were searched: "Fluid Therapy"; "Resuscitation"; "Resuscitation Orders"; "Ultrasonography"; "Diagnostic Imaging"; "Ultrasonography, Doppler"; "Ultrasonography, Interventional"; "Echocardiography"; "Echocardiography, Doppler, Pulsed"; "Echocardiography, Doppler, Color"; "Echocardiography, Doppler"; "Echocardiography, Transesophageal"; "Heart-Lung Machine"; "Lung"; "Vena Cava, Inferior"; "Sepsis"; "Shock, Septic"; "Randomized Controlled Trial". The literature was managed by EndNote X9.

Inclusion and Exclusion Criteria

Inclusion criteria were as follows: (1) randomized controlled trials (RCTs); (2) adult patients (over 18 years of age) with a definitive diagnosis of septic shock; (3) initial fluid resuscitation in the emergency room or ICU; (4) the intervention group was evaluated by ultrasound during initial resuscitation, including hemodynamics, fluid responsiveness, and cardiopulmonary function, etc. ; (5) the control group received the initial resuscitation method recommended by the guidelines for SSC; and (6) other treatments between the two groups should be comparable. Case reports, retrospective studies, observational studies, animal studies, repeated studies, and studies irrelevant to our outcomes of interest were excluded.

Study selection

Two authors (Z-YC and XH) independently screened the titles and abstracts of the articles and further evaluated the eligible articles. If there was any dispute, they would discuss it with the third author (B-BW).

Data extraction and assessment

Two authors (Z-YC and XH) extracted all data independently, and the third person (B-BW) checked the data. These data included first author, year of publication, country, type of study design, number of cases, treatment versus control group, and primary outcome data. Relevant data were collected using Excel tables. Quantitative data were expressed as mean and standard deviation (mean ± SD, \(\stackrel{-}{X}\)±S), and binary data were expressed as frequency or percentage. Medians and quartiles were converted to mean and standard deviation using the method provided by Sean McGrath et al. [23]. The quality of the included studies was evaluated in terms of the method of random allocation, concealment of the allocation scheme, blinding, incomplete outcome data, selective reporting of outcomes, and other sources of bias by the Cochrane Collaboration recommended. It was classified as low, moderate, and high quality and was shown in green, yellow and red [24].

Outcomes

The primary outcome was mortality during the study period. Secondary outcomes included 24-hour fluid volume, vasoactive drug dose or duration, length of hospital stay, ICU stay, and others.

Statistical and analysis

Dichotomous and continuous data were calculated using Mantel-Haenszel (M-H) risk ratios (RR), and Inverse-Variance (IV) mean differences (MD), respectively, with 95% confidence intervals (CI), and estimates of effects were summarized by forest plots. Except for adverse events, all results were evaluated in the meta-analysis. Heterogeneity among studies was assessed by using Cochran Q-statistic (P < 0.10 considered statistically significant), I², and visual inspection of forest plots. A fixed-effects model was performed when I² < 50%; otherwise, the random-effects model was used. In addition, funnel plots were used to assess for potential publication bias across outcomes over 10 studies. Subgroup analysis was performed according to different ultrasound strategies with significant heterogeneity. Qualitative analysis was performed when it was challenging to perform subgroup analysis. In addition, a sensitivity analysis was performed. All relevant data were analyzed using RevMan 5.4.1 (The Cochrane Collaboration, 2020) and STATA 17.0 (StataCorp, 2021).

Study selection

There were 1309 papers initially obtained after searching, and 23 relevant studies were also searched from the clinical trial registration website. A total of 89 papers were duplicated and excluded. After reading the article titles and abstracts, 1218 irrelevant studies were excluded. After reading the complete text, four similar studies were published by the same research team, two studies without relevant endpoints, one study in children, three studies without critical care ultrasound-guided fluid resuscitation, one study without septic shock, and two studies without comparing the ultrasound guidance with early goal-directed therapy were further excluded. Finally, 12 studies were included (Fig. 1).

Study characteristics

A total of 947 participants, of whom 473 were treated with critical care ultrasound-guided fluid resuscitation, were included [19, 20, 25–34] (Table 1).

Nine studies reported fluid volume, of which six reported 24-hour fluid volume as mean ± SD [27, 28] and median with interquartile range [20, 25, 29, 33], one reported 24-hour fluid balance [32], one reported target titration of fluids [30], and one reported 6-hour infusion volumes [26]. Three studies reported the dose of norepinephrine by "µg/kg/h" [27, 30] and the maximum dose [26], one reported the duration of norepinephrine [29], and one reported the total dose of norepinephrine over 24 hours [28]. Two studies respectively reported the dose of dobutamine [27, 30] and the number of participants [26, 33]. Three studies reported the duration of vasopressin [26, 27, 30], one reported without infusion duration [20], and one reported the participants who infusion it in the first 6 hours [25].

Length of stay was expressed as a mean ± SD in two studies [19, 30] and median with interquartile range in three studies [20, 25, 27]. Length of ICU stay was expressed as median with interquartile range in three studies [26, 27, 29], the median in one study [32], and mean ± SD in one study [30]. Length of stay free ICU admission was reported in two studies [20, 33].

Table 1

The characteristics of studies included
	Country, SC / MC ¹	No. of Patients	Intervention	Male (%)	Mean age (years)	APACHE II / SOFA ³ score at baseline	Primary outcome / Primary end‑points
Alhabashy (2021)	Ireland SC	87	CCUGFR EGDT²	57.1 51.1	42.33 ± 8.96 44.44 ± 7.65	(A) 23.95 ± 3.45 24.76 ± 4.26	30-day mortality
Elsayed (2020)	Egypt SC	60	CCUGFR EGDT	56.7 53.3	38.6 ± 3.3 39.4 ± 3.7	(A) 25.4 ± 3.7 25.5 ± 3.7	30-day mortality
Garg (2016)	India SC	36	CCUGFR EGDT	55.6 44.4	37.39 ± 15.53 44.5 ± 18.73	(A) 21.38 ± 9.61 20.66 ± 7.39	IVCCI <20%; MAP of ≥ 65 mmHg and CVP >12 mmHg⁴
Ismail (2019)	Egypt SC	80	CCUGFR EGDT	55.0 42.5	56 58	- -	reach a score of 16 according to the ultrasound scoring system CVP of 8–12 mmHg
Lanspa (2018)	USA SC	30	CCUGFR EGDT	47.0 53.0	69(61–77) 64(49–75)	(A)29(23–41) 33 (31–41)	changed in SOFA score at 48 h
Li (2019)	China SC	74	CCUGFR EGDT	46.0 48.6	62.1 ± 15.3 64.2 ± 17.5	- -	CVP of 8–12 mmHg, MAP ≥ 65 mmHg, urine volume ≥ 0.5 mL/kg/h, and ScvO2 ⁵ ≥ 0.70 within 6 hours
Li (2021)	China SC	94	CCUGFR EGDT	49.0 62.2	54.5 ± 15.2 56.7 ± 11.0	(A) 20.8 ± 8.2 21.8 ± 6.7	28-day mortality
Musikatavorn (2021)	Thailand SC	202	CCUGFR EGDT	52.5 62.4	65.3 ± 20.1 63.7 ± 16.8	- -	30-day mortality
Qi (2020)	China SC	68	CCUGFR EGDT	77.8 75	65.5(50–72) 67(50.5–73)	(A) 18(18-20.5) 19.5(18-24.5)	in-hospital mortality rate, 90-day survival rate
Sricharoenchai (2019)	Thailand SC	90	CCUGFR EGDT	- -	- -	(SO) 4(3–6) 4(3–6)	the 30-day all-cause mortality
Yu (2022)	China SC	86	CCUGFR EGDT	71.4 63.6	54.1 ± 15.4 57.8 ± 15.7	(A) 22.2 ± 6.1 23.6 ± 5.5	the lactate clearance rate (LCR) at 6 h
Zhuang (2020)	China SC	40	CCUGFR EGDT	40.0 55.0	71.6 ± 11.3 71.6 ± 19.2	(SO) 12.2 ± 5.1 14.3 ± 5.0	6-hour blood pressure achieved rate (MAP ≥ 65 mmHg), 24-hour resuscitation fluid volume
All results are present in mean (median if not reported).
¹ MC: multicenter, SC: single-center.
² CCUGFR: critical care ultrasound-guided fluid resuscitation, EGDT: early goal directed therapy.
³ (A) –APACHE II, acute physiology and chronic health evaluation II, (SO)–SOFA score, Sepsis-related Organ Failure score.
⁴ IVCCI: Inferior vena cava collapsibility index, MAP: mean arterial pressure, CVP: central venous pressure.

⁵ ScvO2: Systemic central venous blood oxygen saturation.

Primary Outcome

The mortality was analyzed using a fixed-effects model (Fig. 2). Critical care ultrasound-guided fluid resuscitation was associated with lower mortality (RR 0.78; 95% CI, 0.65, 0.94; P = 0.007). The heterogeneity between studies was low (I² = 0%, P = 0.45). The funnel plot analysis indicated no significant publication bias for mortality (Supplementary Fig. 6). The sensitivity analysis showed that the mortality was reliable (Supplementary Fig. 7).

Secondary Outcomes and Subgroup Analysis

The 24-hour fluid volume was analyzed using a fixed-effects model (Fig. 3a). The fluid volume at 24 hours was significantly reduced in critical care ultrasound-guided fluid resuscitation (MD -1.02; 95%CI, -1.28, -0.75; P < 0.001) with low heterogeneity (I² = 0%, P = 1.00).

Norepinephrine dose was analyzed using a fixed-effect model (Fig. 3b). The dose of norepinephrine was increased in critical care ultrasound-guided fluid resuscitation (MD 0.07; 95%CI, 0.02, 0.11; P = 0.002). The heterogeneity was low (I² = 45%, P = 0.18). The dobutamine dose was analyzed using a fixed-effects model (Fig. 3c). The dobutamine dose was increased (MD 2.2; 95% CI, 0.35, 4.04; P = 0.02). The heterogeneity with low (I² = 0%, P = 0.61). The number of dobutamine users was analyzed using a fixed-effects model (Fig. 3d). Critical care ultrasound-guided fluid resuscitation did not reduce the risk of dobutamine users (RR 1.67; 95%CI, 0.52, 5.36; P = 0.39). The heterogeneity was low (I² = 0%, P = 0.86). The duration of vasopressin infusion was analyzed using a random-effects model (Fig. 3e). The duration of vasopressin infusion was not significantly changed by critical care ultrasound-guided fluid resuscitation (MD -5.46; 95%CI, − 38.78, 27.86; P = 0.75). The heterogeneity was high (I² = 97%, P < 0.001). Due to only a small number of studies included, subgroup analysis was difficult. Thus, a single study effect analysis was adopted. Taking LVOT-VTI, passive leg raising test, IVC-related measures, or only IVC-related measures to evaluate fluid responsiveness was able to have an advantage in the duration of vasopressin infusion [26, 27]. A study revealed that using LVOT-VTI assessing stroke volume and stroke volume variability as fluid responsiveness could not shorten the duration of vasopressin infusion [30].

Length of hospital stay was analyzed using a random-effects model (Fig. 3f). Critical care ultrasound-guided fluid resuscitation did not shorten the length of hospital stay (MD -2.19; 95%CI, -6.28, 1.91; P = 0.29). The heterogeneity was high (I² = 91%, P < 0.001). Thus, we performed subgroup analyses (Figs. 4). According to different ultrasound indicators for monitoring, they were divided into two groups: IVC-related measures and echocardiography. After removing this factor, the results showed that IVC-related measures could reduce the length of hospital stay (MD -2.91; 95%CI, -5.2, -0.62; P = 0.01). The heterogeneity was low (I² = 8%, P = 0.34). However, the heterogeneity in the echocardiography group was high (I² = 97%, P < 0.001). Qualitative analysis showed that using passive leg raising test combined with echocardiography to assess fluid reactivity showed superiority in the length of hospital stay [19]. Length of ICU stay was analyzed using a random-effects model (Fig. 3g). Critical care ultrasound-guided fluid resuscitation also did not reduce the length of ICU stay (MD -0.71; 95%CI, -4.43, 3.02; P = 0.71). The heterogeneity was high (I² = 85%, P < 0.001). We also performed subgroup analyses of the ICU stay by different ultrasound strategies (Figs. 5). The results showed that IVC-related measures or IVC-related measures combined with others could reduce the length of ICU stay (MD -2.77; 95%CI, -4.51, -1.02; P = 0.002), with low heterogeneity (I² = 0%, P = 0.57). Length of free ICU stay treatment was analyzed using a fixed-effects model (Fig. 3h). Critical care ultrasound-guided fluid resuscitation did not significantly change the length of free ICU stay (MD 1.5; 95% CI, − 3.81, 6.81; P = 0.58). The heterogeneity was low (I² = 0%, P = 0.55).

Sensitivity analyses showed that secondary outcomes, including 24-hour fluid volume, norepinephrine dose, dobutamine dose, number of dobutamine users, length of hospital stay, length of ICU stay, and free ICU stay were credible (Supplementary Figs. 8–11, 13–15), but not the duration of vasopressin infusion (Supplementary Fig. 12). Publication bias was not evaluated due to only a small number of studies included in the secondary outcome.

Few meta-analyses have compared critical care ultrasound-guided fluid resuscitation with early goal-directed therapy in patients with septic shock. This systematic review and meta-analysis of 12 studies comprehensively reviewed RCTs published in recent years, and subgroup analyses or qualitative assessments were performed for outcomes with more significant heterogeneity.

We found that critical care ultrasound-guided fluid resuscitation in septic shock patients can reduce mortality. In secondary outcomes, critical care ultrasound-guided fluid resuscitation in patients with septic shock reduced 24-hour fluid volume, increased norepinephrine and dobutamine doses, and did not reduce the number of patients using dobutamine. Moreover, taking IVC-related measures and passive leg raising test combined with LVOT-VTI, or IVC-related measures, to evaluate fluid responsiveness had advantageous in reducing the duration of vasopressin. The increasing dose of vasoactive drugs in the critical care ultrasound-guided fluid resuscitation group, which may maintain organ tissue perfusion by reducing the amount of fluid, will bring more side effects. Vasoactive drugs also play an essential role in the treatment of septic shock. In clinical practice, vasoactive drugs are required when blood pressure cannot maintain organ and tissue perfusion even by adequate fluids. Vasoactive drugs regulate vascular tone through some receptors to improve fluid distribution and tissue perfusion and avoid fluid overload [35].

There was no significant advantage of critical care ultrasound-guided fluid resuscitation in the length of hospital and ICU stay. However, these results were heterogeneous, which may be related to different critical care ultrasound strategies. Therefore, we divided the critical care ultrasound measures into two groups with IVC-related indicators and without these. In subgroup analysis, the critical care ultrasound study with IVC-related measures could significantly reduce the length of hospital stay and ICU stay, especially using passive leg raising test combined with others to assess fluid reactivity showing superiority in the length of hospital stay. The use of dynamic indicators, including echocardiography to guide fluid resuscitation, is weakly recommended in Surviving Sepsis Campaign, and the quality of the evidence is deficient. Other organ and volume responsiveness indicators for monitoring have not been proposed [10]. Subgroup analysis showed that IVC-related measures such as the diameter and morphological variability of the IVC combined with others to guide fluid resuscitation had a better prognosis than echocardiography alone.

Sepsis is a disordered manifestation of the body's systemic inflammatory response to infection, and septic shock is a severe form of sepsis. Although new therapies have been sought in recent years, the results have mainly been disappointing [36]. Early identification of sepsis, especially septic shock, and timely treatment are essential to reducing mortality and complications [10]. Compared to the 2016 SSC guideline, the 2021 SSC guideline did not change the initial fluid resuscitation for patients in septic shock. However, it downgraded the recommendation of fluid volume for early resuscitation in sepsis from a strong recommendation to a weak recommendation [10, 37]. Initial fluid resuscitation has been a highly controversial issue, and most of recommendations are based on clinical practice in multiple extensive studies. The need for early fluid resuscitation in patients with sepsis-induced hypotension or septic shock is based on their pathophysiological changes. The source of fluid resuscitation is the early hypovolemic state of the patient due to systemic vasodilation and increased vascular permeability. Therefore, fluid resuscitation can restore intravascular volume, increase cardiac output, and improve oxygen delivery to improve tissue perfusion [38]. It should make physicians think about using the guideline to individualize therapy. Not all volume expansion effects are as we expect. Due to individual differences in patients, organ function and volume responsiveness are essential in determining whether fluid resuscitation plays a therapeutic or detrimental effect [39]. In recent years, critical care ultrasound has played an increasingly important role, running through the whole process of diagnosis and treatment of critical patients. It has become a part of standard practice in ICU [40]. As a non-invasive monitoring method, critical care ultrasound can effectively assess patient organ function and volume responsiveness [41]. As a dynamic indicator for monitoring volume responsiveness, IVC-related measures can represent right atrial pressure and indicator for cardiopulmonary interaction to guide fluid therapy with higher accuracy. However, it should be noted that IVC-related measures for monitoring are also affected by many factors, such as diseases affecting the return of blood to the right heart, venous thrombosis, and compression of blood vessels [42]. LVOT-VTI is an ultrasound assessment of hemodynamics by Doppler-derived measure of cardiac output and stroke volume [43]. Although it has been found in several studies to predict fluid responsiveness, it has some drawbacks, particularly in severe aortic regurgitation or obstruction, arrhythmias, and there will be severe errors in the measurement [44, 45]. Vignon, P et al. compared several ultrasound indicators for monitoring fluid responsiveness in mechanically ventilated patients and found that the LVOT-VTI has the highest sensitivity and measuring the diameter of the superior vena cava and respiratory variability has the highest specificity, which is better than IVC-related measures and LVOT-VTI [46]. For measurement accuracy, we should take appropriate measures according to its characteristics, even use more than one measure to assess fluid responsiveness.

Of course, this systematic review and meta-analysis also has some limitations. Most RCTs are single-center studies, lacking higher-quality RCTs. In addition, there is heterogeneity among some of the included studies, and the same outcome may be expressed in different ways. It is challenging to combine them, resulting in fewer studies for some secondary outcomes and limited certainty.

This systematic review and meta-analysis, as we know, is the most comprehensive to date, describing a comparison of critical care ultrasound-guided fluid resuscitation with early goal-directed therapy in patients with septic shock. Critical care ultrasound-guided fluid resuscitation in septic shock patients can reduce mortality and 24-hour fluid volume and increase vasoactive drugs' dose. The critical care ultrasound strategy with IVC-related measures can reduce the length of hospital and ICU stay. Taking LVOT-VTI, passive leg raising test, IVC-related measures, or only IVC-related measures to evaluate fluid responsiveness was advantageous. Therefore, critical care ultrasound-guided fluid resuscitation can improve the prognosis of patients with septic shock. Using ultrasound strategies, including IVC-related measures, LVOT-VTI, and passive leg raising test guiding fluid resuscitation may be more effective.

SSC: Surviving Sepsis Guideline; EGDT: Early goal-directed therapy; CCUGFR: Critical care ultrasound-guided fluid resuscitation; ICU: Intensive care unit; IVC: Inferior vena cava; IVCCI: Inferior vena cava collapsibility index; LVOT-VTI: Left ventricular outflow tract velocity time integral; RCTs: Randomized controlled trials; mean±SD: Mean and standard deviation; M-H: Mantel-Haenszel; RR: Risk ratios; IV: Inverse-Variance; MD: Mean differences; CI: Confidence intervals; MC: Multicenter; SC: Single-center; A: APACHE II, acute physiology and chronic health evaluation II; SO: SOFA score, Sepsis-related Organ Failure score; MAP: Mean arterial pressure; CVP: Central venous pressure; ScvO2: Systemic central venous blood oxygen saturation

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and materials

All data generated or analysed during this study are included in this published article and its supplementary information files.

Competing interests

All authors declare no competing interests.

Funding

This research received no funding.

Authors' contributions

Z-YC conceived the study, participated in the design, acquired data, and drafted the manuscript. XH conceived the study, extracted data, and performed the statistical analysis. YL and M-JW participated in data interpretation and final drafting of the manuscript. B-BW worked on collecting data and designing the study. LW contributed to the study's design, and H-XJ edited and examined the manuscript. All authors read and approved the final manuscript.

Acknowledgements

The authors' gratitude Xing-shun Qi, MD, for giving consultations about this study.

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No competing interests reported.

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Critical care ultrasound-guided fluid resuscitation versus early goal-directed therapy in patients with septic shock: A systematic review and Meta-analysis

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