Predictive accuracy of changes in the inferior vena cava diameter for predicting fluid responsiveness in patients with sepsis: A systematic review and meta-analysis

Hao Zhang; Jingyuan Jiang; Min Dai; Yan Liang; Ningxiang Li; Yongli Gao

doi:10.1371/journal.pone.0310462

. 2025 May 9;20(5):e0310462. doi: 10.1371/journal.pone.0310462

Predictive accuracy of changes in the inferior vena cava diameter for predicting fluid responsiveness in patients with sepsis: A systematic review and meta-analysis

Hao Zhang ^1,^2,^3,^‡, Jingyuan Jiang ^1,^2,^3,^‡, Min Dai ^1,^2,³, Yan Liang ^1,^2,³, Ningxiang Li ^1,^2,³, Yongli Gao ^1,^2,^3,^*

Editor: Vincenzo Lionetti⁴

PMCID: PMC12064207 PMID: 40344560

Abstract

Background

Existing guidelines emphasize the importance of initial fluid resuscitation therapy in sepsis management. However, in previous meta-analyses, there have been inconsistencies in differentiating between spontaneously breathing and mechanically ventilated septic patients.

Objective

To consolidate the literature on the predictive accuracy of changes in the inferior vena cava diameter (∆IVC) for fluid responsiveness in septic patients.

Methods

The Embase, Web of Science, Cochrane Library, MEDLINE, PubMed, Wanfang, China National Knowledge Infrastructure (CNKI), Chinese Biomedical (CBM) and VIP (Weipu) databases were comprehensively searched. Statistical analyses were performed with Stata 15.0 software and Meta-DiSc 1.4.

Results

Twenty-one research studies were deemed suitable for inclusion. The sensitivity and specificity of ∆ IVC were 0.84 (95% CI 0.76, 0.90) and 0.87 (95% CI 0.80, 0.91), respectively. With respect to the distensibility of the inferior vena cava (dIVC), the sensitivity was 0.79 (95% CI 0.68, 0.86), and the specificity was 0.82 (95% CI 0.73, 0.89). For collapsibility of the inferior vena cava (cIVC), the sensitivity and specificity values were 0.92 (95% CI 0.83, 0.96) and 0.93 (95% CI 0.86, 0.97), respectively.

Conclusion

The results indicated that ∆IVC is as a dependable marker for fluid responsiveness in sepsis patients. dIVC and cIVC also exhibited high levels of accuracy in predicting fluid responsiveness in septic patients.

Introduction

A 2017 study published in The Lancet reported that there were over 48 million cases of sepsis worldwide [1], with a 90-day mortality rate of 35.5% among septic ICU patients [2], resulting in an estimated 5.3 million deaths annually [3]. Sepsis and septic shock, which cause severe acute impairment and deterioration of survivors’ chronic health status, have emerged as significant global public health concerns [4,5]. Existing guidelines [6–8] emphasize the importance of initial fluid resuscitation therapy in sepsis management, as this treatment increases cardiac output, enhances organ and tissue perfusion, and reduces mortality [9]. Previous studies have shown that, either alone or in combination, static assessment indicators of fluid responsiveness are not sufficient to accurately and dynamically assess the fluid responsiveness of fluid resuscitation in septic patients, although they can be the most intuitive clinical judgment through physical examination[10,11].The existing guidelines recommend evaluating the patient’s circulatory status via dynamic indicators during the initial fluid resuscitation procedure to select additional treatment choices [6–8]. However, determining the optimal volume and target endpoints for fluid resuscitation remains challenging for frontline intensivists in clinical practice [12]. Excessive fluid replacement can lead to serious complications, including tissue edema, hypoxia, and cardiac failure, which can exacerbate clinical outcomes and potentially increase mortality [13,14]. Thus, accurate, objective, and effective dynamic index monitoring methods are essential for evaluating fluid responsiveness in septic patients.

Point-of-care ultrasound (POCUS) is essential for managing sepsis volume because of its convenient and noninvasive monitoring capabilities in real time. Numerous problems, including bleeding and infection, may arise from the invasive procedures and specialized monitoring equipment needed to quantify dynamic parameters such as the stroke volume variation (SVV), volume variability index (PVI), and pulse pressure variation (PPV) [15,16]. This technology helps minimize the dangers of invasive procedures and specialized monitoring equipment. The inferior vena cava (IVC), which is the largest vein in the human body, is linked to right atrial pressure and blood volume. Consequently, the IVC serves as a crucial focal point during ultrasound evaluations of hemodynamics [17–18]. The IVC index obtained through ultrasound serves as a measure of the efficiency of systemic venous return to the heart. The primary purpose of this index to assess the correlation between venous return volume and cardiac function.

Multiple studies have investigated the prognostic importance of changes in the IVC diameter (∆IVC) for fluid reactivity in hospitalized patients in critical condition. Long et al. [19] found that (∆IVC) had limited predictive ability for fluid reactivity among critically ill patients who were breathing spontaneously. According to the study conducted by Kim et al. [20], alterations in the diameter of the IVC provide reliable diagnostic precision for forecasting liquid reactivity in spontaneously breathing critically ill individuals. Si et al. [21] proposed that ∆IVC had improved diagnostic accuracy among mechanically ventilated patients when the tidal volume (TV) was ≥ 8 ml/kg compared to a TV ≤ 8 ml/kg. Alvarado et al. [22] reported that ∆IVC had good predictive performance for fluid responsiveness in critically ill adult patients on mechanical ventilation with a TV ≤ 8 ml/kg and without dyspnea or arrhythmia. However, there are still inconsistencies in terms of differentiating between spontaneously breathing and mechanically ventilated septic patients. For mechanically ventilated patients, ∆ IVC was referred to as inferior vena cava distensibility (dIVC), and for spontaneously breathing patients, it was referred to as inferior vena cava collapsibility (cIVC). This study aimed to consolidate the literature on the predictive accuracy of changes in IVC diameter for liquid reactivity among septic individuals, thus highlighting the importance of the IVC in managing volume in sepsis patients.

Materials and methods

This systematic review and meta-analysis carried out was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis of Diagnostic Test Accuracy (PRISMA-DTA) statement [23]. The study protocol was formally registered in PROSPERO with the registration number CRD42023469308 to maintain transparency and reliability.

Selection criteria

(1) The inclusion criteria included studies published in Chinese and English that focused on patients with sepsis or septic shock. The research subjects in the original literature should identify whether they are mechanically ventilated or spontaneously breathing patients. Mechanically ventilated patients should collect ventilator parameters.
(2) The diagnostic method involved measuring patients’ ∆ IVC via ultrasound. ∆ IVC was also referred to as dIVC and cIVC. The purpose of this study was to assess the predictive accuracy of ultrasonographic measurements of ∆ IVC for fluid responsiveness in patients with sepsis, utilizing measures such as sensitivity, specificity, true positives (TPs), true negatives (TNs), false positives (FPs), and false negatives (FNs).
(3) The exclusion criteria were as follows: expectant females, individuals younger than 18 years of age, duplicate publications, studies lacking data for a 2x2 chart, review articles, conference presentations, case studies, and animal research.

Search strategy

The Embase, Web of Science, Cochrane Library, MEDLINE, PubMed, Wanfang, CNKI, CBM and VIP databases were comprehensively searched from inception to February 29, 2024. The search strategy was as follows: (sepsis) OR (sepsis-associated encephalopathy) OR (systemic inflammatory response syndrome) OR (neonatal sepsis) OR (bloodstream infection) OR (infection bloodstream)) AND (inferior vena cava diameter) OR (IVC) OR (inferior vena cava distensibility index) OR (inferior vena cava collapsibility index) OR (inferior vena cava respiratory variation index) OR (dIVC) OR (cIVC) OR (IVC-RVI) OR (caval index)) AND (fluid administration) OR (fluid resuscitation) OR (fluid responsiveness) OR (fluid reactivity) OR (volume responsiveness)). PubMed database which showed in Fig 1.

Study selection

During the first round of the study selection process, two independent reviewers examined the titles and abstracts of the citations, extracted the data and performed cross-verification. Two researchers conducted the screening and data extraction on the basis of the literature, and any disagreements were resolved by discussion with a third researcher. Endnote X9 was utilized to manage the literature. The initial screening involved reviewing the article title, followed by assessing the abstract and full text to determine eligibility, excluding any obvious inconsistencies. The following data were extracted: the first author; the source of publication; the date of publication; the duration of the study; the type of study conducted; demographic information about the study population; sample size; sensitivity; specificity; TP, FP, TN, and FN rates; diagnostic methods for fluid reactions; and diagnostic thresholds.

Assessment of quality

Two separate researchers evaluated the risk of bias in the included literature. Any disagreements were resolved by discussion or by consulting a third party. The quality of the literature was evaluated using the QUADAS-2 tool [24], which assesses aspects such as bias risk and clinical relevance. This tool consists of three tiers and 14 sections.

Statistical analysis

We conducted the statistical analysis via Stata 15.0 software and Meta-DiSc 1.4. In studies demonstrating heterogeneity, Meta-DiSc 1.4 was utilized to examine threshold effects. We performed Spearman’s correlation analysis and merged effect size indicators in cases without a threshold effect. Meta-analysis was performed using Stata 15.0, which yielded the sensitivity, specificity, summary receiver operating characteristic curve (AUC), positive likelihood ratio (PLR), diagnostic odds ratio (DOR), negative likelihood ratio (NLR), and a forest plot. The evaluation of publication bias was conducted through the utilization of Deeks’ funnel plot. Fagan plots were used to analyze the clinical importance of IVC respiratory variability in predicting liquid reactivity. For the subgroup analysis, we first compared mechanically ventilated and nonmechanically ventilated individuals. We analyzed various ventilator parameters including TV, PEEP, and threshold, which are mechanically ventilated.

Results

Search results

A total of 885 papers were initially identified across nine databases. By removing 18 duplicates with the help of the Endnote X9 tool and then excluding 833 more through screening, the full texts of the remaining 34 citations were thoroughly reviewed. Ultimately, 21 research studies were deemed suitable for inclusion, including 14 studies published in English and 7 studies published in Chinese [25–45]. (Fig 2).

Characteristics of the included studies

A total of 21 articles encompassing 1207 patients with sepsis were reviewed. Of these, 15 articles focused on dIVC, whereas six focused on cIVC. (Tables 1 and 2).

Table 1. Main characteristics of the eligible studies.

Author	Year	Country	Device	Measure Site	Fluid challenge	Reference Standard	vasopressors	MV	MV setting	Index Test	Study period	Threshold	Sample Size
Shen	2019	China	US (CX50, Holland)	2 cm from right atrium	500ml NS/LR over 20min	CO > 10%	yes	yes	/	dIVC	2017.05 ~ 2018.10	16.5%	50
Gao	2021	China	US (Viv-id E9,USA)	M-model,2 cm the hepatic vein joins the inferior vena cava	7 ml/kg of LR over 20min	CI ≥ 15%	yes	yes	VT = 6 ~ 10ml/kg	dIVC	2019.01 ~ 2020.02	17.65%	27
Yao	2020	China	US (Sonosite,USA)	M-model, 2 cm from right atrium	500 mL 6% hydroxyethyl starch over 30min	CI ＞ 15%	yes	yes	VT = 10ml/kg	dIVC	2018.10 ~ 2019.10	28%	70
Zhang	2022	China	US (Resona7,China)	/	/	CI ≥ 15%	/	yes	/	dIVC	2020.01 ~ 2021.12	15.7%	110
Chen	2023	China	US (vivid E9,USA)	/	/	CI > 10%	yes	yes	/	dIVC	2018.01 ~ 2020.12	11.77%	98
Zhu	2016	China	US (Sonosite,USA)	M-model, 2 cm from right atrium	500 mL of 6% hydroxyethyl starch/NS over 30min	SV ≥ 15%	yes	yes	/	dIVC	2013.06 ~ 2015.08	19.25%	58
Lu	2018	China	/	2 cm from right atrium	200ml NS over 10min	CI ≥ 10%	yes	yes	/	dIVC	2016.01 ~ 2017.12	20.5%	65
Orhan	2022	Turkey	US (Esaote,Italy)	M-model, 2 cm from right atrium	10 mL/kg of crystalline solution baseline and 15min	CO ≥ 15%	no	yes	VT = 8ml/kg,PPEP = 5 cmH₂O	dIVC	2018.06.26 ~ 2019.07.01	17.52	40
Charbonn	2014	France	US (Suresnes,France)	M-model, Directly above the hepatic vein junction	7 ml/kg of 6% hydroxyethyl starch 15 min	CI ≥ 15%	yes	yes	VT = 8 ~ 10ml/kg	dIVC	/	21	44
Lu	2017	China	US (Sonosite, USA)	M-model, 2 cm from right	200 mL NS over 10min	CI ≥ 10%	yes	yes	VT = 8 ~ 10ml/kg, PEEP = 5 ~ 12 cmH₂O	dIVC	2012.01 ~ 2015.12	20.5	49
Theerawit	2016	Thailand	US (SonoSite,USA)	M-model, 2 cm from right atrium	1000 ml NS/500 ml 6% hydroxyethyl starch/5% human albumin over 30min	CO ≥ 15%	yes	yes	VT ≥ 8ml/kg PEEP = 8 ~ 10 cmH₂O	dIVC	2012.11 ~ 20.13.12	10.2	29
Saber	2022	Egypt	/	M-model, 2 cm from right atrium	500mL NS 10min, Two measurements。	CO ≥ 15%	yes	yes	VT = 6 ~ 8ml/kg, PEEP = 0 ~ 5 cmH₂O	dIVC	2017.10 ~ 2018.10	14.5	40
Feissel	2004	France	/	M-model, 3 cm from right atrium	8ml/kg 6% hydroxyethyl starch 20min	CO ≥ 15%	/	yes	VT ≥ 8 ~ 10 mL/kg	dIVC	/	12	39
Abdelma	2023	Egypt	US(GE HealthCare Vivid,USA)	/	30ml/kg of crystalline solution	CO ≥ 15%	yes	yes	VT = 8ml/kg,PEEP = 5 cmH₂O	dIVC	2021.09 ~ 2022.03	13.3	34
He	2023	China	US(Zonare,USA)	the IVC under the raphe	200 mL NS over 10min	SV ≥ 15%	/	yes	PEEP = 4 cmH₂O	dIVC	2018.04 ~ 2021.02	16.5	102
Preau	2017	France	US(vivid-i/Vivid-S5,USA)	1.5 to 2 cm Hepatic vein junction with IVC/3–4 cm from right atrium	500ml 4% Gelatin over 30min	SV ≥ 15%	yes	no	/	cIVC	2011.11 ~ 2014.01	48	90
Zhao	2016	China		2 cm Hepatic vein junction with IVC	500 ml 6% hydroxyethyl starch 30min	CI ≥ 15%	yes	no	/	cIVC	2013.10 ~ 2014.03	12.9	42
Caplan	2020	France	US(Vivid-i/Vivid-S5,USA)	4 cm from right atrium	500ml 4% Gelatin over 30min	SV ≥ 10%	yes/NE	no	/	cIVC	2011.11 ~ 2015.05	44	81
Elsaeed	2022	Egypt	US(GE,USA)	M model lower edge of the ribcage	7 ml/kg of LR over 30min	CI ≥ 15%	no	no	/	cIVC	/	35	40
Murat	2016	Turkey	US(Philips EPIQ 5,USA)	M model, 0.5 to 3 cm from right atrium-hepatic vein junction	PLR	CI ≥ 15%	/	no	/	cIVC	/	35	44
Perrine	2018	France	US(vivid-i/Vivid-S5,USA)	1.5 to 2 cm Hepatic vein junction with IVC/3–4 cm from right atrium	500ml 4% Gelatin over 30min	Velocity time integral≥10%	yes/NE	no	/	cIVC	2012.05 ~ 2015.05	39	55

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Ultrasonographic = US, inferior vena cava = IVC, inferior vena cava diameter = ∆IVC, inferior vena cava distensibility = dIVC, inferior vena cava collapsibility = cIVC, MV = mechanical ventilation; PEEP = positive end expiratory pressure, tidal volume = VT, NS = Normal saline, PLR = passive leg raising, CO = cardiac output, CI = cardiac index, SV = stroke volume,/ = not reported, NE = Norepinephrine.

Table 2. 2-by-2 table of the eligible studies.

Author	Year	TP	FP	FN	TN	Total	Sensitivity	Specificity	AUC
Shen	2019	20	7	5	18	50	80%	72%	0.777
Gao	2021	19	1	0	7	27	100.00%	87.50%	0.924
Yao	2020	34	2	5	29	70	87.20%	93.10%	0.94
Zhang	2022	44	7	22	37	110	66.00%	85.00%	0.709
Chen	2023	53	28	3	14	98	95.08%	34.14%	0.664
Zhu	2016	17	3	15	23	58	53.10%	88.50%	0.733
Lu	2018	19	4	12	30	65	60.30%	89.70%	0.826
Orhan	2022	18	5	5	12	40	77.50%	72.50%	0.833
Charbonn	2014	10	7	16	11	44	38%	61%	0.43
Lu	2017	18	5	9	17	49	67%	77%	0.805
Theerawit	2016	12	3	4	10	29	75%	76.90%	0.688
Saber	2022	17	2	3	18	40	85%	90%	0.913
Feissel	2004	15	2	1	21	39	93%	92%	/
Abdelma	2023	21	0	2	11	34	91.30%	100%	0.925
He	2023	35	7	19	41	102	65.4	84.9	0.858
Preau	2017	42	4	8	36	90	84%	90%	0.89
Zhao	2016	32	0	0	10	42	100%	100%	0.917
Caplan	2020	38	1	3	39	81	93%	98%	0.98
Elsaeed	2022	23	1	1	15	40	95.8	93.7	0.97
Murat	2016	18	3	5	18	44	78%	85%	0.825
Perrine	2018	27	3	2	23	55	93%	88%	0.93

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true positives = TP, false positives = FP, false negatives = FN, true negatives = TN, area under the receiver operating characteristic curve = AUC.

Assessment of quality

Using Review Manager 5.3 software, the quality of all included studies was assessed using the QUADAS-2 tool. The findings indicated that the literature was generally high-quality, with potential biases regarding patient selection, the index test, and the reference standard (Figs 3 and 4).

Statistical analysis

Threshold effect test.

The threshold effect test was performed using Meta-DiSc 1.4 software. The results revealed Spearman correlation coefficients of -0.440 (P = 0.046) for ∆ IVC, -0.157 (P = 0.576) for dIVC, and -0.543 (P = 0.266) for cIVC. These findings suggest a potential threshold effect on ∆ IVC, whereas no threshold effect was observed on dIVC and cIVC, allowing their effect sizes to be combined.

Meta-analysis.

The sensitivity and specificity of ∆ IVC were 0.84 (95% CI 0.76, 0.90) and 0.87 (95% CI 0.80, 0.91), respectively. The sensitivity and specificity of dIVC were 0.79 and 0.82, respectively. The sensitivity and specificity of cIVC were 0.92 and 0.93, respectively. The results for the other indicators are presented in detail in Table 3. The forest plots depicting the results of the meta-analysis are provided in the appendix of the manuscript (Figs 5-16).

Table 3. ∆ IVC, dIVC and cIVC of meta-analysis.

Group	sensitivity	specificity	PLR	NLR	DOR	AUC
∆IVC	0.84	0.87	6.26	0.18	34.03	0.92
∆IVC	0.76 ~ 0.90	0.80 ~ 0.91	3.93 ~ 9.97	0.12 ~ 0.29	15.09 ~ 76.76	0.89 ~ 0.94
dIVC	0.79	0.82	4.42	0.26	17.10	0.88
dIVC	0.68 ~ 0.86	0.73 ~ 0.89	2.83 ~ 6.92	0.17 ~ 0.40	8.10 ~ 36.09	0.84 ~ 0.90
cIVC	0.92	0.93	13.52	0.09	156.62	0.97
cIVC	0.83 ~ 0.96	0.86 ~ 0.97	6.16 ~ 29.66	0.04 ~ 0.19	40.11 ~ 611.56	0.95 ~ 0.98

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positive likelihood ratio = PLR, negative likelihood ratio = NLR, diagnostic odds ratio = DOR, area under the receiver operating characteristic curve = AUC.

Fig 16 — SENS = sensitivity, SPEC = specificity, AUC = area under the receiver operating characteristic curve.

Fig 8 — ∆ IVC. SENS = sensitivity, SPEC = specificity, AUC = area under the receiver operating characteristic curve.

Fig 12 — SENS = sensitivity, SPEC = specificity, AUC = area under the receiver operating characteristic curve.

In Deeks’ funnel plots, the values were 0.28, 0.23, and 0.60, indicating that the included studies had no publication bias (Figs 17-19). The 50% predictive probability results were 86%, 82%, and 93%, and the negative posttest probabilities were 16%, 21%, and 8%, respectively (Figs 20-22).

Currently, there is no evidence that a single evaluation parameter or index can be utilized as an endpoint on its own to direct fluid resuscitation in sepsis patients. Our subgroup analysis is based on previous systematic review results, basic ventilator parameters (TV = 6-8mL/kg, PEEP = 5 cmH2O), and dose selection for fluid resuscitation. Each enrolled patient with septic shock was categorized into the low-volume (200ml), medium-volume (7 mL/kg fluid), or high-volume (above 500 mL) fluid group according to the infusion volume. We conducted subgroup analyses based on TV, PEEP, infusion volume, and diagnostic threshold. A meta-regression analysis was conducted on ∆ IVC in the dIVC and cIVC, revealing a statistically significant difference of SE = 2.022 (95% CI: 1.81–31.48, P = 0.0081), which could account for the observed heterogeneity. Subgroup analyses were then performed based on TV(P = 0.580), PEEP(P = 0.732), infusion volume(P = 0.417), and diagnostic threshold (P = 0.472) in the dIVC, as well as infusion volume(P = 0.791) and diagnostic threshold (P = 0.846) in the cIVC. The analyses did not yield significant results (Tables 4–5).

Table 4. dIVC of Subgroup analyses.

Subgroup	sensitivity	specificity	PLR	NLR	DOR	AUC	Meta-regression (P value)
VT(ml/kg)							0.580
≥8	0.75	0.82	3.92	0.28	16.30	0.885
≥8	0.68 ~ 0.82	0.75 ~ 0.88	1.81 ~ 8.50	0.13 ~ 0.58	4 ~ 66.49	0.816
≤8	0.85	0.85	5.61	0.20	30.96	0.888
≤8	0.74 ~ 0.92	0.74 ~ 0.92	1.58 ~ 19.85	0.11 ~ 0.36	5.52 ~ 173.68	0.819
PEEP(cmH₂O)							0.732
PEEP≤5	0.76	0.85	4.49	0.26	18.67	0.871
PEEP≤5	0.67 ~ 0.83	0.77 ~ 0.92	2.36 ~ 8.54	0.14 ~ 0.47	6.36 ~ 54.81	0.802
PEEP≥5	0.78	0.79	3.07	0.30	10.79	0.819
PEEP≥5	0.67 ~ 0.86	0.67 ~ 0.89	1.90 ~ 4.99	0.18 ~ 0.50	4.10 ~ 28.38	0.753
Infusion volume							0.417
500ml	0.780	0.870	5.130	0.240	23.230	0.895
500ml	0.71 ~ 0.84	0.79 ~ 0.92	2.75 ~ 9.57	0.13 ~ 0.45	8.84 ~ 61.7	0.826
200ml	0.64	0.85	4.02	0.42	9.78	0.753
200ml	0.55 ~ 0.73	0.76 ~ 0.91	2.52 ~ 6.43	0.33 ~ 0.55	5.05 ~ 18.97	0.696
≥7ml/kg	0.740	0.770	3.190	0.220	16.780	0.806
≥7ml/kg	0.63 ~ 0.83	0.65 ~ 0.87	1.12 ~ 9.08	0.04 ~ 1.08	1.51 ~ 186.11	0.741
Threshold (%)							0.472
≤16.5	0.79	0.75	4.25	0.27	14.95	0.856
≤16.5	0.73 ~ 0.83	0.69 ~ 0.81	1.98 ~ 9.11	0.19 ~ 0.40	8.14 ~ 27.47	0.787
＞16.5	0.69	0.83	3.53	0.40	10.81	0.872
＞16.5	0.62 ~ 0.75	0.76 ~ 0.88	1.87 ~ 6.64	0.24 ~ 0.66	3.51 ~ 33.33	0.802

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positive likelihood ratio = PLR, negative likelihood ratio = NLR, diagnostic odds ratio = DOR, area under the receiver operating characteristic curve = AUC.

Table 5. cIVC of Subgroup analyses.

Subgroup	sensitivity	specificity	PLR	NLR	DOR	AUC	Meta-regression (P value)
Infusion volume							0.791
500ml	0.89	0.93	9.61	0.14	93.09	0.974
500ml	0.83 ~ 0.94	0.86 ~ 0.97	4.36 ~ 21.21	0.06 ~ 0.29	19.52 ~ 443.89	0.926
7ml/kg	0.958	0.937	/	/	/	0.970
7ml/kg	/	/	/	/	/	0.861 ~ 0.999
PLR	0.93	0.88	/	/	/	0.930
	0.77 ~ 0.99	0.69 ~ 0.97	/	/	/	0.86 ~ 0.10
Threshold (%)							0.846
＞35	0.89	0.92	10.07	0.12	101.73	0.960
	0.82 ~ 0.94	0.86 ~ 0.97	4.87 ~ 20.80	0.06 ~ 0.23	28.81 ~ 359.19	0.906
≤35	0.92	0.91	7.91	0.08	138.52	0.960
	0.84 ~ 0.97	0.80 ~ 0.978	3.28 ~ 19.09	0.01 ~ 0.49	10.72 ~ 1789.77	0.903

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positive likelihood ratio = PLR, negative likelihood ratio = NLR, diagnostic odds ratio = DOR, area under the receiver operating characteristic curve = AUC.

Discussion

This study analyzed a total of 21 papers involving 1207 septic patients. This meta-analysis is the first study to assess the predictive value of cIVC and dIVC for liquid reactivity among septic individuals who are mechanically ventilated and spontaneously breathing. The findings indicated that ∆IVC had good overall performance in predicting fluid reactivity in septic patients, with a combined sensitivity, specificity, and AUC of 0.84, 0.87, and 0.92, respectively, exceeding the values reported in previous systematic reviews [19,20,46–48].

The subgroup analysis could not determine the effect of vasopressors on fluid resuscitation because only two of the assessed studies included patients who did not receive vasopressors. Vasopressors and fluid resuscitation are essential components of hemodynamic support for treating patients with septic shock [49]. Vasopressors may also be utilized until fluid resuscitation is finished, according to ESICM recommendations [6]. According to previous research, treating patients with septic shock necessitates multiangle assessment, individualized treatment, quantified and targeted fluid management and assessment, and prudent and standardized use of vasopressors, all of which are helpful in the resuscitation of patients experiencing early septic shock [50].

A rational fluid approach necessitates that we view septic shock as a multiphase illness, and numerous indicators or techniques are combined on the basis of the patient’s volume responsiveness. Subgroup analyses by Long [19] et al. and Kim et al. [20]. demonstrated that ∆IVC was an effective predictor of fluid reactivity, with AUCs of 0.85 and 0.87, respectively; however, ∆ IVC did exhibit lower sensitivity. The cIVC showed excellent performance in terms of predicting fluid reactivity in spontaneously breathing septic individuals, displaying superior diagnostic accuracy compared with the dIVC in mechanically ventilated septic patients. This finding is consistent with the study by Orso et al. [47] but contrary to those of Zhang et al. [46], Long et al. [19] and Kim et al. [20], possibly due to the inclusion of a diverse range of critically ill patients. However, Long et al. [19]. and Orso et al. [47]. included both adults and children in their studies. Since children have different physiological characteristics, such as vascular compliance, respiratory rate, and TV, than adults, caution should be taken when comparing and analyzing the results.

The latest edition of the Sepsis and Infectious Shock Guidelines, which was published by the Surviving Sepsis Campaign, recommends the use of dynamic measurements to assess fluid responsiveness [6]. Ultrasound is utilized for hemodynamic evaluation with a focus on volume. The IVC, which is the largest venous trunk in the body, is closely linked to right atrial pressure and blood volume. It is pliant and easily dilated, and its internal diameter and degree of collapse are used to evaluate volume status in critically ill patients [51]. ∆ IVC provides a comprehensive three-dimensional assessment of the internal diameter of the IVC, aligning with current practices. Meta-regression analysis of ∆ IVC among different respiratory tract types revealed significant differences, with dIVC and cIVC potentially contributing to the observed heterogeneity. While ∆IVC was termed dIVC and cIVC in mechanically ventilated and spontaneously breathing patients, respectively, subgroup analyses in related studies revealed differences only in respiratory or disease types, thus lacking a solid scientific basis for volume assessment in septic patients. Studies have suggested that the ∆ IVC performs better in predicting fluid responsiveness in mechanically ventilated patients than in spontaneously breathing patients [19,20,46], possibly because of factors such as hypovolemia or changes in intrathoracic pressure during respiration. dIVC has shown promise in predicting fluid responsiveness in mechanically ventilated septic patients, with higher sensitivity, specificity, and AUC values than those reported in previous studies. This improvement may be attributed to the inclusion of more recent studies in the analysis. This mechanism arises from the varying breathing patterns of patients, leading to distinct trends in the variation in the inner diameter of the inferior vena cava during inspiration [52]. Among individuals who breathe spontaneously, negative pressure is present in the chest at the end of expiration. Fluctuations in intrathoracic pressure can result in a decrease in pressure within the right atrium, thereby increasing the speed of venous return. Conversely, during mechanical ventilation, the intrathoracic pressure increases during the inspiratory phase. This elevation in pressure results in an increase in right atrial pressure, which subsequently obstructs venous return.

The determination of fluid responsiveness via dIVC was more accurate in septic patients with ventilator parameters of TV ≤ 8 ml/kg or PEEP ≤5 cmH₂O than in those with TV ≥ 8 ml/kg or PEEP ≥5 cmH₂O. However, meta-regression analysis of TV and PEEP did not reveal any significant moderators, and subgroup analysis did not yield any statistically significant differences. These findings align with a study conducted by Alvarado et al. [22]. The results reported by Si et al. [21] were also consistent with our results with respect to PEEP, but those authors reported opposite results concerning tidal volume. In mechanically ventilated patients, the ventilator controls inspiratory flow, resulting in positive pressure and elevated intrathoracic pressure and leading to changes in the IVC diameter [53]. Studies have shown that the use of low TV ventilation modes in septic patients can improve pulmonary oxygenation and reduce airway pressure, thereby lowering the risk of lung injury. Additionally, larger TV may lead to alveolar overdistension, impair pulmonary blood flow perfusion, and redistribute fluids, ultimately compromising the effectiveness of fluid resuscitation [54]. Research indicates that appropriate PEEP can enhance alveolar ventilation, improve oxygenation, and reduce the incidence of pulmonary edema. However, excessively high PEEP may decrease cardiac return, adversely affecting hemodynamics and increasing fluid demands [55]. It is crucial to optimize respiratory conditions through precise ventilator settings to ensure lung protection while avoiding excessive fluid overload. For example, if chest ultrasound demonstrates adequate cardiac preload but PEEP settings result in insufficient circulation, adjustments to fluid administration may be necessary. However, when a patient experiences excessive circulating volume load, the inner diameter of the inferior vena cava expands, and the amplitude of its movement diminishes. Previous studies have several limitations, such as small sample sizes and a lack of differentiation between spontaneously breathing and mechanically ventilated septic patients. A more comprehensive study on ventilator parameter settings is necessary to validate these results.

In septic patients, ∆ IVC was found to be more effective than the comparison group in terms of predicting fluid responsiveness with a 500-ml infusion volume and a dIVC threshold >16.5%. However, a dIVC threshold >16.5% had a sensitivity of 0.69, which was lower than that of the comparison group. Subgroup analysis of the cIVC threshold did not reveal significant differences in diagnostic efficacy. Meta-regression analysis revealed that none of the moderators were significant, and no statistically significant differences were observed. The studies included dIVC and cIVC thresholds ranging from 10.2 to 28 and 12.9 to 48, respectively. Changes in the chest wall and lung compliance may impact pulse pressure changes but do not affect volume status, potentially altering thresholds and accuracy of assessment [56]. Corl et al. [57] studied 124 spontaneously breathing critically ill patients in the ICU by measuring the IVC diameter before and after 500 ml of fluid rehydration and reported that an IVC dilatation index >25% predicted increased cardiac output postfluid infusion in spontaneously breathing patients. The area under the curve was 0.84. Airapetian et al. [58] reported 97% sensitivity and 31% specificity in predicting fluid response in autonomously breathing patients when the ∆ IVC was > 42%. According to the Frank–Starling curve, only approximately 50% of patients are volume-responsive enough to benefit from aggressive fluid resuscitation [59]. Small-volume liquid infusion inevitably decreases the critical values of C0, CI and other indicators for judging volume responsiveness, which requires researchers to have very skilled ultrasound technology to reduce errors caused by operation and subjective judgment. Using threshold-guided fluid resuscitation to guide fluid resuscitation in patients with sepsis can more effectively increase the patient’s cardiac output and correct and maintain the intracellular and extracellular electrolyte balance [9]. Patients with septic shock who complete 30 mL/kg fluid resuscitation within 1–2 hours can significantly reduce 28-day mortality while improving organ function [60]. Fluid overload on ICU day 1 may lower in-hospital mortality risk but could increase mortality after day 3. This indicates that early adequate fluid resuscitation is beneficial, whereas strict fluid restriction in later phases is critical to avoid excessive overload [61]. A high fluid balance is associated with increased mortality in severe sepsis and septic shock patients, while low-volume resuscitation within the initial 24 hours markedly reduces mortality. This suggests that lower fluid resuscitation thresholds may be safer for certain patient populations. Lauralyn et al. [62] suggest that critically ill patients exhibit significant heterogeneity, rendering standardized therapeutic measures increasingly controversial and challenging both theoretically and practically. Initial fluid resuscitation should adhere to an individualized approach. The four-phase resuscitation strategy requires close coordination and timely adjustments based on the patient’s clinical status. However, ineffective implementation persists due to clinicians’ failure to strictly follow guidelines and insufficient clinical experience.

Limitations

First, heterogeneity in measurement protocols primarily arises from differences between mechanically ventilated and non-ventilated patient cohorts. Second, critically ill patients demonstrate significant heterogeneity that those with heart failure, kidney disease, or other comorbidities may exhibit marked variations in fluid resuscitation efficacy. This necessitates the integration of dynamic parameters, such as ultrasound-guided assessments combined with pulse pressure variation (PPV) or fluid challenge tests, when evaluating fluid resuscitation in septic patients. Additionally, blood lactate levels should be combined to comprehensively assess resuscitation outcomes. Furthermore, the impact of concomitant vasopressor use during fluid resuscitation on the trial results must be considered in our study.

Conclusion

The findings demonstrate that selecting parameters with tidal volume ≤8 mL/kg, PEEP ≤5 cmH₂O, and fluid volume ≥500 mL is more effective for accurately assessing fluid resuscitation in mechanically ventilated septic patients. For non-ventilated septic patients, maintaining a fluid volume ≥500 mL remains clinically significant. Overall, ∆ IVC showed strong predictive value for liquid reactivity in septic individuals, with the dIVC and cIVC displaying good and excellent accuracy in predicting fluid reactivity in mechanically ventilated and spontaneously breathing septic individuals.

Supporting information

S1. Checklist Table for the present systematic review.

(DOCX)

pone.0310462.s001.docx^{(31.8KB, docx)}

S2. PRISMA_2020_checklist for the present systematic review.

(DOCX)

pone.0310462.s002.docx^{(31.8KB, docx)}

S3. Supplementary information-1.xlsx.

(XLSX)

pone.0310462.s003.xlsx^{(438.2KB, xlsx)}

Acknowledgments

We thank all authors of the included studies to help us get the data required in this meta-analysis.

Data Availability

All data are in the manuscript and/or supporting information files.

Funding Statement

The author(s) received no specific funding for this work.

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Vincenzo Lionetti, M.D., PhD

Academic Editor

PLOS ONE

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A numbered table of all studies identified in the literature search, including those that were excluded from the analyses.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

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PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Dear authors

Appreciated for this effort of reviewing literature related to IVC diameter changes and its relation to fluid responsiveness prediction.

Your efforts are well done.

I just suggest to give more elaboration on the different observation of outcome effect between dIVC and cIVC from physiological point.

Additionally did you ascertain that vasopressors were not manipulated during fluid challenge in included studies as this might affect the standard reference of CI or CO.

Thanks

Reviewer #2: Revisions to improve usefulness:

1. Provide a more detailed discussion of the clinical implications of the different ΔIVC, dIVC, and cIVC thresholds used across studies. What guidance can be given to clinicians on choosing appropriate cutoffs?

2. Expand the analysis and discussion of potential sources of bias in the included studies, particularly related to patient selection and index test conduct.

3. Include a more thorough explanation of the observed heterogeneity between studies and its implications for interpreting the pooled results.

4. Provide clearer guidance on how clinicians should integrate these IVC measurements with other clinical parameters when assessing fluid responsiveness.

5. Discuss any limitations in the generalizability of these findings to different sepsis patient populations or clinical settings.

6. Consider including a proposed algorithm or decision tree for using IVC measurements in clinical practice based on the synthesis of evidence from this review.

Introduction:

The introduction provides a good overview of the clinical importance of fluid management in sepsis and the potential role of IVC measurements. However, it could be strengthened by:

・Providing more context on current guidelines for fluid management in sepsis and their limitations.

・Clarifying the specific advantages of IVC measurements over other methods of assessing fluid responsiveness.

Methods:

The methods section is generally well-described, but could be improved by:

・Providing more detail on the search strategy, including full search terms for each database.

・Clarifying the criteria used for assessing study quality and how this information was incorporated into the analysis.

・Explaining how discrepancies in data extraction or quality assessment between reviewers were resolved.

Results:

The results are comprehensively presented, but some aspects could be clarified:

・The rationale for the chosen subgroup analyses could be more explicitly stated.

・More detail on the results of the quality assessment for individual studies would be helpful.

・A more in-depth exploration of the sources of heterogeneity would strengthen the analysis.

Discussion:

The discussion provides a good overview of the findings, but could be enhanced by:

・A more critical analysis of the limitations of the included studies and how these might impact the overall conclusions.

・More detailed discussion of the clinical implications of the different thresholds used across studies.

・Clearer guidance on how clinicians should integrate these IVC measurements with other clinical parameters when assessing fluid responsiveness.

・A more thorough comparison of these findings with other methods of assessing fluid responsiveness in sepsis.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #1: Yes: Fadi Aljamaan

Reviewer #2: No

**********

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PLoS One. 2025 May 9;20(5):e0310462. doi: 10.1371/journal.pone.0310462.r003

Author response to Decision Letter 1

27 Nov 2024

Dear Reviewers,

Happy Thanksgiving Day! Thank you for your thorough review and constructive suggestions regarding our manuscript. We have revised the manuscript in accordance with your comments and have marked all amendments in the revised document. In addition to our point-by-point responses to the reviewers’ comments, we have also made every effort to meet the required editorial standards, ensuring that all changes are easily identifiable. We hope that our revised manuscript fulfills your requirements. If any further action is needed, please do not hesitate to let us know. We look forward to your feedback.

1. Please improve english grammar and style of the draft

Response: Considering the academic editor’s suggestion, we have engaged a native English speaker to thoroughly revise our language, ensuring the fluency, accuracy, and consistency of our writing. We believe these changes will greatly enhance the quality of our manuscript.

2. Data Availability Statement

Response: Considering the Reviewer’s suggestion, we have corrected it, and it has been changed to “All data are in the manuscript and/or supporting information files”. Please see the Data Availability Statement in the attachment of Supplementary Material.

3. Literature search section

Response: Considering the Reviewer’s suggestion, we uploaded the files in Excel format of Supplementary information.

4. Suggest to Give more elaboration on the different observation of outcome effect between dIVC and cIVC from physiological point.

Response: Considering the Reviewer’s suggestion, we modified the Introduction and Discussion accordingly and added the following references. As detailed in the Introduction, page 6, lines 100 -103, see Discussion section, page 14, line 278-287.

5. The reviewer raises an important point that vasopressors were not manipulated during fluid challenge in included studies as this might affect the standard reference of CI or CO?

Response: Considering the Reviewer’s suggestion, all members of the research team read all the literatures. We reviewed the full text and found that four literatures did not explicitly mention the use of vasopressors, two literatures excluded patients who were using vasopressors, and the remaining literatures all acknowledged the use of vasopressors during the study period. Subgroup analysis was not feasible due to the limited number of relevant studies. However, this issue is addressed in the Discussion and Limitations sections. Moreover, the details of the literature have been incorporated into Table1 Main characteristics of the eligible studies by the author.

6. Providing more context on current guidelines for fluid management in sepsis and their limitations.

Response: Considering the Reviewer’s suggestion, we modified the Introduction accordingly. As detailed in the Introduction, page 4, lines 57 -64.

7. Clarifying the specific advantages of IVC measurements over other methods of assessing fluid responsiveness.

Response: Considering the Reviewer’s suggestion, we modified the Introduction accordingly. As detailed in the Introduction, page 5, lines 74-78, 82-85.

8. Providing more detail on the search strategy, including full search terms for each database.

Response: Thank you for the comment. We provided a complete search strategy for the PubMed database which showed in Fig 1. We now have elaborated the search strategy in Word format giving the details of Electronic search strategy.

9. Clarifying the criteria used for assessing study quality and how this information was incorporated into the analysis.

Response: Considering the Reviewer’s suggestion, we used the QUADAS 2 tool as a guide to direct our judgments as to the quality of the included studies. ZH scored and recorded for all references using the QUADAS-2 tool, and then DM reviewed the results. More detailed descriptions in the supplementary Excel file were also provided.

10. Explaining how discrepancies in data extraction or quality assessment between reviewers were resolved.

Response: Considering the Reviewer’s suggestion, we modified the Materials and Methods accordingly. In case of disagreement between two researchers in the literature screening or data extraction process, the decision was submitted to the third researcher (GYL). As detailed in the Study selection, page 8, lines 142-144.

11. The rationale for the chosen subgroup analyses could be more explicitly stated.

Response: Considering the Reviewer’s suggestion, we modified the Subgroup analysis accordingly. As detailed in the Subgroup analysis, page 11, lines 210-213.

12. More detail on the results of the quality assessment for individual studies would be helpful.

Response: Considering the Reviewer’s suggestion, we used the QUADAS 2 tool as a guide to direct our judgments as to the quality of the included studies. More detailed descriptions in the supplementary Excel file were also provided.

13. A more in-depth exploration of the sources of heterogeneity would strengthen the analysis.

Response: Considering the Reviewer’s suggestion, we modified the Discussion accordingly. see Discussion section, page 12,14-16.

14. More detailed discussion of the clinical implications of the different thresholds used across studies.

Response: Considering the Reviewer’s suggestion, we modified the Discussion accordingly. see Discussion section, page 16, lines 333-340.

15. Clearer guidance on how clinicians should integrate these IVC measurements with other clinical parameters when assessing fluid responsiveness.

Response: Considering the Reviewer’s suggestion, we modified the Discussion accordingly. see Discussion section, page 14, lines 279-288.

16. A more thorough comparison of these findings with other methods of assessing fluid responsiveness in sepsis.

Response: Considering the Reviewer’s suggestion, we modified the Discussion accordingly. see Discussion section, page 12,14-16.

Attachment

Submitted filename: Response to Reviewers.docx

pone.0310462.s005.docx^{(21.4KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0310462.r004

Decision Letter 1

Vincenzo Lionetti

17 Dec 2024

PONE-D-24-36864R1Predictive accuracy of changes in the inferior vena cava diameter for predicting fluid responsiveness in patients with sepsis: A systematic review and meta-analysisPLOS ONE

Dear Dr. Zhang,

==============================

ACADEMIC EDITOR: Despite some improvement, the revised form requires further clarification in accord with Reviewer's suggestions/>==============================

Please submit your revised manuscript by Jan 31 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

We look forward to receiving your revised manuscript.

Kind regards,

Vincenzo Lionetti, M.D., PhD

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #1: Yes

Reviewer #2: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #1: Yes

Reviewer #2: No

**********

6. Review Comments to the Author

Reviewer #1: Appreciated for the excellent work.

It is still as you mentioned in the limitations that pattern and type of breathing affect the change of dIVC and its predictivity even though you could not find statistical significance with PEEP and VT, but for sure many other non recorded variable may play role.

Reviewer #2: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #1: Yes: Aljamaan, Fadi S

Reviewer #2: No

**********

PLoS One. 2025 May 9;20(5):e0310462. doi: 10.1371/journal.pone.0310462.r005

Author response to Decision Letter 2

29 Dec 2024

Dear Reviewers,

Thank you for your thorough review and constructive suggestions regarding our manuscript. We have revised the manuscript in accordance with your comments and have marked all amendments in the revised document. In addition to our point-by-point responses to the reviewers’ comments, we have also made every effort to meet the required editorial standards, ensuring that all changes are easily identifiable. We hope that our revised manuscript fulfills your requirements. If any further action is needed, please do not hesitate to let us know. We look forward to your feedback.

1. It is still as you mentioned in the limitations that pattern and type of breathing affect the change of dIVC and its predictivity even though you could not find statistical significance with PEEP and VT, but for sure many other non recorded variable may play role.

Response Reviewer #1: Considering the Reviewer’s suggestion, we have expounded more detail in the discussion section, page 13, line 252-255. Based on past research findings, we suggest that this outcome could be attributed to physiological differences between adults and children. They included several studies of pediatric patients, whereas we excluded these studies.

2. Is the manuscript presented in an intelligible fashion and written in standard English?

Response Reviewer #2: Considering the Reviewer’s suggestion, we have engaged a native English speaker to thoroughly revise our language, ensuring the fluency, accuracy, and consistency of our writing. We believe these changes will greatly enhance the quality of our manuscript.

3. Has the statistical analysis been performed appropriately and rigorously?

Response Reviewer #2: This systematic review and meta-analysis was carried out was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis of Diagnostic Test Accuracy (PRISMA-DTA) statement. Based on the given guidelines, we employed the statistical analysis software provided by the instructions to obtain the data results.

4. Have the authors made all data underlying the findings in their manuscript fully available?

Response Reviewer #2: Considering the Reviewer’s suggestion, All of our data, which is open and transparent, has been uploaded to the attachment in Excel tables.

Attachment

Submitted filename: Response to Reviewers-3.docx

pone.0310462.s006.docx^{(17.1KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0310462.r006

Decision Letter 2

Vincenzo Lionetti

7 Jan 2025

PONE-D-24-36864R2Predictive accuracy of changes in the inferior vena cava diameter for predicting fluid responsiveness in patients with sepsis: A systematic review and meta-analysisPLOS ONE

Dear Dr. Zhang,

==============================

ACADEMIC EDITOR:

The authors are encouraged to reply to all comments by one reviewer.

==============================

Please submit your revised manuscript by Feb 21 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

We look forward to receiving your revised manuscript.

Kind regards,

Vincenzo Lionetti, M.D., PhD

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #2: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #2: Yes

**********

6. Review Comments to the Author

Reviewer #2: This systematic review and meta-analysis examines the predictive accuracy of inferior vena cava (IVC) measurements for fluid responsiveness in septic patients. The study analyzed 21 papers (1,207 patients), evaluating three key parameters: overall IVC diameter changes (∆IVC), IVC distensibility (dIVC) in mechanically ventilated patients, and IVC collapsibility (cIVC) in spontaneously breathing patients. The results demonstrated good diagnostic accuracy across all measures, with particularly strong performance of cIVC in spontaneously breathing patients. However, there are some concerns needing revision.

Methodology:

1. The selection criteria differentiating mechanically ventilated from spontaneously breathing patients needs clearer exposition

2. The heterogeneity in ventilator parameters across studies requires more detailed analysis

3. The rationale for subgroup analysis thresholds should be better justified

Results Presentation:

1. Forest plots and funnel plots should be integrated into the main text rather than supplementary materials for better readability

2. The discussion of varying thresholds across studies needs expansion

3. The implications of different fluid challenge protocols require more detailed analysis

4. The meta-regression results need clearer presentation, particularly regarding the clinical significance of findings

Discussion:

1. The limitations section should be expanded to address:

- Heterogeneity in study protocols

- Variations in measurement techniques

- Impact of different patient populations

2. Clinical implementation challenges need more thorough discussion

3. Specific recommendations for standardizing measurement techniques should be included

4. The implications of different ventilator settings need more detailed analysis

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #2: No

**********

PLoS One. 2025 May 9;20(5):e0310462. doi: 10.1371/journal.pone.0310462.r007

Author response to Decision Letter 3

23 Feb 2025

Dear Editors,

Thank you for your thorough review and constructive suggestions regarding our manuscript. We sincerely appreciate the time and effort you dedicated to reviewing and providing feedback. In particular, we highly value the constructive suggestions you made, which were carefully discussed within our team. We fully agree with your recommendations and have made detailed revisions accordingly. These improvements will help enhance the manuscript’s quality and ensure it meets the standards for publication. Once again, thank you for your valuable input, which has greatly contributed to this research. We look forward to your feedback. Below are our point-by-point responses to your comments:

Methodology:

1. The selection criteria differentiating mechanically ventilated from spontaneously breathing patients needs clearer exposition.

Response academic editor: Thank you once again for your constructive feedback. We greatly appreciate and value your insights. In response, we have revised and enhanced the Methodology section. Your valuable input has improved the completeness of the description.

The manuscript has been amended to state: “The inclusion criteria included studies published in Chinese and English that focused on patients with sepsis or septic shock. The research subjects in the original literature should identify whether they are mechanically ventilated or spontaneously breathing patients. Mechanically ventilated patients should collect ventilator parameters.”

2. The heterogeneity in ventilator parameters across studies requires more detailed analysis

Response academic editor: Thank you for your valuable suggestion. In response, we have revised the Methodology section accordingly. And it has been changed to “For the subgroup analysis, we first compared mechanically ventilated and nonmechanically ventilated individuals. We analyzed various ventilator parameters including TV, PEEP, and threshold, which are mechanically ventilated.”

3. The rationale for subgroup analysis thresholds should be better justified

Response academic editor: Thank you for your helpful suggestion. In response, we have revised the Methodology section accordingly. The manuscript has been amended to state: “Currently, there is no evidence that a single evaluation parameter or index can be utilized as an endpoint on its own to direct fluid resuscitation in sepsis patients. Our subgroup analysis is based on previous systematic review results, basic ventilator parameters (TV=6-8mL/kg, PEEP=5 cmH2O), and dose selection for fluid resuscitation. Each enrolled patient with septic shock was categorized into the low-volume (200ml), medium-volume (7 mL/kg fluid), or high-volume (above 500 mL) fluid group according to the infusion volume. We conducted subgroup analyses based on TV, PEEP, infusion volume, and diagnostic threshold.”

Results Presentation:

1. Forest plots and funnel plots should be integrated into the main text rather than supplementary materials for better readability

Response academic editor: Thank you for your insightful comment and helpful suggestions. In response, we have revised the forest plots and funnel plots accordingly.

2. The discussion of varying thresholds across studies needs expansion?

Response academic editor: Thank you for your insightful comment and helpful suggestions. In response, we have revised the Results and Discussion section accordingly.

3. The implications of different fluid challenge protocols require more detailed analysis.

Response academic editor: Thank you for your insightful suggestion. In response, we have revised the Results and Discussion section accordingly.

4. The meta-regression results need clearer presentation, particularly regarding the clinical significance of findings.

Response academic editor: Thank you for your helpful suggestion. In response, we have revised the Results and Discussion section accordingly.

Discussion Presentation:

1. The limitations section should be expanded to address: Heterogeneity in study protocols, Variations in measurement techniques, Impact of different patient populations.

Response academic editor: Thank you for your helpful suggestion. In response, we have revised the Limitations section accordingly.

“First, heterogeneity in measurement protocols primarily arises from differences between mechanically ventilated and non-ventilated patient cohorts. Second, critically ill patients demonstrate significant heterogeneity that those with heart failure, kidney disease, or other comorbidities may exhibit marked variations in fluid resuscitation efficacy. This necessitates the integration of dynamic parameters, such as ultrasound-guided assessments combined with pulse pressure variation (PPV) or fluid challenge tests, when evaluating fluid resuscitation in septic patients. Additionally, blood lactate levels should be combined to comprehensively assess resuscitation outcomes.”

2. Clinical implementation challenges need more thorough discussion.

Response academic editor: Thank you for your thoughtful suggestion. In response, we have revised the Discussion section accordingly.

3. Specific recommendations for standardizing measurement techniques should be included.

Response academic editor: Thank you for your suggestion. In response, we have revised the Discussion section accordingly.

4. The implications of different ventilator settings need more detailed analysis.

Response academic editor: Thank you for your suggestion. In response, we have revised the Discussion section accordingly.

Attachment

Submitted filename: Response_to_Reviewers_auresp_3.docx

pone.0310462.s007.docx^{(22.3KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0310462.r008

Decision Letter 3

Vincenzo Lionetti

17 Mar 2025

Predictive accuracy of changes in the inferior vena cava diameter for predicting fluid responsiveness in patients with sepsis: A systematic review and meta-analysis

PONE-D-24-36864R3

Dear Dr. Zhang,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Vincenzo Lionetti, M.D., PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #2: Yes

**********

6. Review Comments to the Author

Reviewer #2: After reviewing the revised manuscript, I find that the authors have addressed the major concerns raised in the previous review. The improvements to the methodology, results presentation, and discussion sections have significantly enhanced the quality and clarity of the manuscript.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #2: No

**********

PLoS One. doi: 10.1371/journal.pone.0310462.r009

Acceptance letter

Vincenzo Lionetti

PONE-D-24-36864R3

PLOS ONE

Dear Dr. Zhang,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

* All references, tables, and figures are properly cited

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Supplementary Materials

S1. Checklist Table for the present systematic review.

(DOCX)

pone.0310462.s001.docx^{(31.8KB, docx)}

S2. PRISMA_2020_checklist for the present systematic review.

(DOCX)

pone.0310462.s002.docx^{(31.8KB, docx)}

S3. Supplementary information-1.xlsx.

(XLSX)

pone.0310462.s003.xlsx^{(438.2KB, xlsx)}

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Data Availability Statement

All data are in the manuscript and/or supporting information files.

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PERMALINK

Predictive accuracy of changes in the inferior vena cava diameter for predicting fluid responsiveness in patients with sepsis: A systematic review and meta-analysis

Hao Zhang

Jingyuan Jiang

Min Dai

Yan Liang

Ningxiang Li

Yongli Gao

Roles

Abstract

Background

Objective

Methods

Results

Conclusion

Introduction

Materials and methods

Selection criteria

Search strategy

Fig 1. Search strategy of PubMed database.

Study selection

Assessment of quality

Statistical analysis

Results

Search results

Fig 2. Flowchart of study selection.

Characteristics of the included studies

Table 1. Main characteristics of the eligible studies.

Table 2. 2-by-2 table of the eligible studies.

Assessment of quality

Fig 3. Quality assessment of diagnostic accuracy studies criteria for the included studies.

Fig 4. Quality assessment of diagnostic accuracy studies criteria for the included studies.

Statistical analysis

Threshold effect test.

Meta-analysis.

Table 3. ∆ IVC, dIVC and cIVC of meta-analysis.

Fig 5. Forest plot of sensitivity and specificity in the diagnosis of .

Fig 16. Summary receiver operator characteristic (SROC) curve in the prediction of cIVC.

Fig 6. Forest plot of PLR and NLR in the diagnosis of .

Fig 7. Forest plot of DOR in the diagnosis of .

Fig 8. Summary receiver operator characteristic (SROC) curve in the prediction of .

Fig 9. Forest plot of sensitivity and specificity in the diagnosis of dIVC.

Fig 10. Forest plot of PLR and NLR in the diagnosis of dIVC.

Fig 11. Forest plot of DOR in the diagnosis of dIVC.

Fig 12. Summary receiver operator characteristic (SROC) curve in the prediction of dIVC.

Fig 13. Forest plot of sensitivity and specificity in the diagnosis of cIVC.

Fig 14. Forest plot of PLR and NLR in the diagnosis of cIVC.

Fig 15. Forest plot of DOR in the diagnosis of cIVC.

Fig 17. Deek’s funnel plots of ∆ IVC.

Fig 19. Deek’s funnel plots of cIVC.

Fig 20. Fangan plots of .

Fig 22. Fangan plots of cIVC.

Fig 18. Deek’s funnel plots of dIVC.

Fig 21. Fangan plots of dIVC.

Table 4. dIVC of Subgroup analyses.

Table 5. cIVC of Subgroup analyses.

Discussion

Limitations

Conclusion

Supporting information

Acknowledgments

Data Availability

Funding Statement

References

Author response to Decision Letter 0

Decision Letter 0

Vincenzo Lionetti

Roles

Author response to Decision Letter 1

Decision Letter 1

Vincenzo Lionetti

Roles

Author response to Decision Letter 2

Decision Letter 2

Vincenzo Lionetti

Roles

Author response to Decision Letter 3

Decision Letter 3

Vincenzo Lionetti

Roles