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Fluid Resuscitation in Sepsis a Systematic Review and Network Meta-analysis

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Resuscitation fluid types in sepsis, surgical, and trauma patients: a systematic review and sequential network meta-analyses

  • Tzu-Tao Chenfour,
  • Mei-Yi Wu5,6,
  • Ming-Cheng Chan7,8,
  • Ming-Chieh Shih1 &
  • Yu-Kang Tu ORCID: orcid.org/0000-0002-2461-474X 1,nine,10

Critical Care volume 24, Commodity number:693 (2020) Cite this article

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Abstract

Background

Crystalloids and different component colloids, used for volume resuscitation, are sometimes associated with various adverse effects. Clinical trial findings for such fluid types in different patients' weather condition are conflicting. Whether the bloodshed do good of balanced crystalloid than saline tin exist inferred from sepsis to other patient grouping is uncertain, and adverse upshot profile is not comprehensive. This study aims to compare the survival benefits and adverse effects of seven fluid types with network meta-assay in sepsis, surgical, trauma, and traumatic brain injury patients.

Methods

Searched databases (PubMed, EMBASE, and Cochrane Primal) and reference lists of relevant articles occurred from inception until Jan 2020. Studies on critically sick adults requiring fluid resuscitation were included. Intervention studies reported on balanced crystalloid, saline, iso-oncotic albumin, hyperoncotic albumin, low molecular weight hydroxyethyl starch (L-HES), high molecular weight HES, and gelatin. Network meta-analyses were conducted using random-effects model to calculate odds ratio (OR) and mean deviation. Risk of Bias tool 2.0 was used to assess bias. Confidence in Network Meta-Analysis (Movie house) web application was used to rate confidence in constructed bear witness.

Results

Fifty-eight trials (northward = 26,351 patients) were identified. Seven fluid types were evaluated. Among patients with sepsis and surgery, balanced crystalloids and albumin achieved better survival, fewer astute kidney injury, and smaller claret transfusion volumes than saline and L-HES. In those with sepsis, balanced crystalloids significantly reduced bloodshed more saline (OR 0.84; 95% CI 0.74–0.95) and L-HES (OR 0.81; 95% CI 0.69–0.95) and reduced acute kidney injury more than L-HES (OR 0.80; 95% CI 0.65–0.99). However, they required the greatest resuscitation book amongst all fluid types, specially in trauma patients. In patients with traumatic encephalon injury, saline and 50-HES achieved lower mortality than albumin and balanced crystalloids; especially saline was significantly superior to iso-oncotic albumin (OR 0.55; 95% CI 0.35–0.87).

Conclusions

Our network meta-analysis found that counterbalanced crystalloids and albumin decreased bloodshed more L-HES and saline in sepsis patients; withal, saline or 50-HES was amend than iso-oncotic albumin or balanced crystalloids in traumatic encephalon injury patients.

Trial registration

PROSPERO website, registration number: CRD42018115641).

Introduction

Fluid resuscitation is i of the about common and important methods in managing critically hypotensive patients. Crystalloids, mineral salts, or other water-soluble molecule solutions have been used for more than than 100 years for fluid resuscitation [i, 2]. In the past decades, several colloids, larger insoluble molecular solutions, accept been developed to ameliorate intravascular volume more than effectively. Withal, since the integrity of the endothelial glycocalyx layer might be interrupted nether inflammatory atmospheric condition, such equally sepsis, surgery, trauma, or traumatic brain injury, evaluation of the efficacy and safe of colloids in such patients is challenging [iii, 4].

Insoluble molecules in colloids include starch, bovine protein (gelatin), and man protein (albumin). Hydroxyethyl starch (HES) of college molecular weight has a longer half-life in plasma, but it reduces plasma coagulation factors more than HES of lower molecular weight [5] and albumin [6]. Starch macromolecule accumulation likewise impairs glomerular filtration and is associated with a higher risk of astute renal failure than gelatin [vii]; however, gelatin is associated with a higher incidence of anaphylactic daze [8, 9]. Compared to iso-oncotic albumin, hyperoncotic albumin leads to a college osmotic pressure, which may alter intraglomerular oncotic force and osmotic nephrosis, and is associated with worse kidney harm [10]. Chemical components, molecular weights, and colloid concentration might expose the homo trunk to different levels of hazards [11]. Among crystalloids, saline worsens acidosis and haemorrhage trend compared to balanced crystalloids [12]. Consequently, classifying resuscitation fluids into either colloids or crystalloids was no longer enough.

From 2012 to 2018, of 15 meta-analyses published on fluid resuscitation in critically ill patients (Additional file 1: appendix pp. v–7), 12 (lxxx%) grouped loftier and low chloride crystalloids or colloids of dissimilar components into a single type of handling, and v (33.3%) grouped sepsis, surgical, and trauma patients into ane meta-assay. Furthermore, no meta-analyses compared the required fluid volumes for the resuscitation target. This study aimed to compare the survival benefit and whatsoever potential agin effects of seven fluid types using network meta-analysis (NMA) in sepsis, surgical, trauma, and traumatic brain injury patients, and investigated the trend in treatment difference using sequential NMA.

Methods

Data sources and searches

We registered our systematic review process on the PROSPERO website [13] (registration number: CRD42018115641). This NMA followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) extension guideline which incorporated NMA for healthcare interventions (Additional file ane: appendix pp. 8–xiii) [xiv]. Electronic databases, including PubMed, EMBASE, and Cochrane CENTRAL, were searched from their inception until January 2020. The search strategies combined terms for patients' weather condition, clinical outcomes, and fluid types (Boosted file ane: appendix pp. 14–15).

Study selection

We included randomized controlled trials (RCTs) on critically ill adult patients (more than 18 years old) who presented with systemic hypoperfusion and required fluid resuscitation. We excluded trials on children with dengue fever, those on burn injury patients, or those on mixed populations without reporting subgroup data (Additional file i: appendix pp. 17–twenty).

Data extraction and quality cess

We divided patients requiring fluid resuscitation into the following groups for extraction of data and separate analyses: sepsis, surgical, trauma, and traumatic brain injury. The 7 interventions included two crystalloids [balanced crystalloids, including lactated Ringer's, Ringer acetate or PlasmaLytes and saline (0.9% sodium chloride)], and 5 colloids [iso-oncotic albumin (four%, 5%); hyperoncotic albumin (20%, or 25%); HES with molecular weight ≦ 130 g (L-HES); HES with molecular weight ≧ 200 k (H-HES); and gelatin]. The outcomes included:

  1. (i)

    All-cause mortality charge per unit. If a study reported outcomes at multiple time points, we chose the longest observation.

  2. (2)

    Fluid resuscitation book. The resuscitation target is the reversal of organ hypoperfusion.

  3. (3)

    Astute kidney injury, referring to the caste of renal dysfunction, based on a v-level scoring organization to evaluate chance, injury, failure, loss, and end-stage renal failure (RIFLE).

  4. (4)

    Transfusion volume.

  5. (5)

    Allergic reaction rate.

Two authors (CH Tseng and TT Chen) screened the studies on RCTs independently, extracted information, and assessed the risk of bias of studies using the revised Cochrane take a chance of bias tool (RoB two tool) at study level [xv]. A third reviewer (YK Tu) was consulted to resolve any disagreement in information extraction or cess.

Data synthesis and analysis

Transitivity supposition was assessed past checking the distribution of potential confounding variables beyond studies grouped by interventions. The variables examined included age, male percentage, illness severity scores, source of sepsis from the lung, and publication year. We first used the "network" suite of STATA version 14.0 [16] (StataCorp, Texas, USA) statistical software, which implements a frequentist arroyo to the contrast-based model meta-analyses [xvi], to undertake a random-effect NMA [17]. We then used network map to illustrate the distribution of the straight and indirect prove between all treatment comparisons. The size of the nodes in the map was proportional to the number of patients who received this intervention in the network, and the width of the edges was proportional to the number of trials that compared the ii treatments. Certainty of the evidence was assessed using CINeMA (Confidence in Network Meta-Analysis) web application, which allows for conviction in the results to be graded as high, moderate, low, and very low. This approach was based on a methodology developed by the Grading of Recommendations Cess, Evolution and Evaluation Working Group for pairwise meta-analyses [xviii].

Surface under the cumulative ranking (SUCRA) probabilities is the ratio of the area under the cumulative ranking bend to the unabridged surface area in the plot. The more quickly the cumulative ranking curve approaches one, the closer to unity this ratio is. SUCRA values may be seen as the per centum of safety a treatment achieves in relation to an imaginary treatment that is always the best without whatsoever uncertainty [19]. To adjust for the multiplicity of statistical testing, we farther conducted sequential NMA, proposed by Nikolakopoulor et al., who extended the rationales of sequential meta-analyses for defining sample-path, efficacy boundaries, futility boundaries, and information size in meta-analyses [20]. In sequential NMA, we undertook a series of NMA, providing a path of estimates for each pairwise comparison, by including studies incrementally into the analysis according to their publication years [twenty]. When the path crossed the efficacy boundaries, defined by the α-spending function derived from the O'Brien–Fleming method [21], the departure betwixt the 2 treatments exceeded the threshold for statistical significance. In dissimilarity, when the path roughshod within the futility area defined by the β-spending functions [22], the two interventions showed no difference in their furnishings. We used the R software package "sequentialnma" to undertake sequential NMA [23]. Results from these additional analyses were then compared to the results from the NMA.

Results

The literature search identified eighteen,802 citations, and 377 full-text articles were assessed for eligibility. Of 58 RCTs which included 26,351 patients in the analysis, 5 large RCTs included more than one status—sepsis, surgery, trauma, and traumatic brain injury. Thus, we extracted the subgroup data of patients with different conditions. As a result, 23 RCTs on sepsis patients, 24 on surgical patients, ten on trauma patients, and 4 on traumatic brain injury patients were included for further analysis (Fig. i, Additional file ane: appendix pp. 17–48). We nowadays the risk of bias assessment for each included study in Additional file 1: appendix 7 (appendix pp. 61–70); eFigure vii.one shows the overall risk of bias in five domains in sepsis trials, eFigure 7.two shows the risk of bias for the individual studies, and eFigure 7.3 explains the reasons for upgrading or downgrading in every report (Additional file 1: appendix pp. 60–63, 64–66, 67–69). The reasons to downgrade are mostly inadequate randomization procedure, open up-labeled design, or no detailed information. No significant differences in baseline variables betwixt interventions were observed inside our NMA (Boosted file 1: appendix pp. 49–60).

Fig. one
figure 1

Summary of prove search and option

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Sepsis patients

Well-nigh RCTs used the 2001 International Sepsis Definitions Briefing sepsis definition [24] and included sepsis patients with shock status or those who had evidence of tissue or organ hypoperfusion (Boosted file 1: eTable 5.2, appendix pp. 23–26). The timing for fluid resuscitation is when the patient meets the enrollment criteria: systemic hypoperfusion defined by depression blood pressure, low primal venous pressure or wedge pressure and elevated lactate level. We compared the mean arterial pressure amid interventions at baseline (Additional file 1: appendix pp. 56), ranging from 69.0 to 73.ix mmHg, and found no statistically significant differences among 7 fluid types. Besides, in Additional file one: eTable 5.4 (appendix pp. 29–31), and Additional file ane: eTable five.6 (appendix pp. 35–36), we compared resuscitation targets among included trials. The resuscitation goals are by and large to maintain wedge pressure level effectually 15–18 mmHg or central venous pressure around eight–12 mmHg. The average mean written report fluid volume was 2397.iv mL ± 1019.1 mL in each arm, and the full resuscitation fluid book was 7615.6 mL ± 1729.7 mL (Additional file one: appendix pp. 22–31, 61–64). In Boosted file i: eTable v.3 (appendix pp. 26–27), we presented the baseline characteristics, including age, severity of illness, mean arterial pressure, and lactate level.

Sepsis patients—mortality

Between 1983 and 2018, 23 RCTs with 14,659 participants presented with usable results on bloodshed. In Additional file 1: appendix eTable 5.1 (Additional file 1: appendix pp. 21), we provided the details of mortality consequence used in our analysis, including in-hospital mortality, 30 day-mortality, and 90-day mortality. If multiple fourth dimension points were reported in a written report, nosotros chose the longest observation period for mortality analysis. Balanced crystalloids reduced bloodshed more than saline and L-HES with odds ratios (OR) of 0.84 (95% CI 0.74–0.95) and 0.81 (95% CI 0.69–0.95), respectively (Fig. 2a). Sequential NMA further supported the difference in mortality rate between counterbalanced crystalloids versus saline and L-HES by demonstrating that the tendency in cumulative evidence exceeded the efficacy boundary. The cumulative evidence exceeded the futility purlieus in the comparison between balanced crystalloids and albumin, but fell between efficacy and futility boundary in the comparison betwixt balanced crystalloids and gelatin (Fig. three). Co-ordinate to SUCRA, balanced crystalloid appeared to be the best option; nonetheless, saline, L-HES, and H-HES were not favored (Fig. four).

Fig. 2
figure 2

Network geometry and forest plot in sepsis patients with iv outcomes. a Bloodshed, b fluid resuscitation corporeality, c acute kidney injury, d transfusion amount. The deviation among each comparing is visualized with forest plot, and the effect size and show rating are labeled on the right-hand side. The assuming characters are to emphasize pregnant contrasts. The 95% conviction intervals in the forest plot are clipped to arrows, when they exceed the limit of ten-axis. Abbreviations: OR odds ratio; *p < 0.0.v; **p < 0.01; H loftier confidence rating, Yard moderate confident rating, L low confidence rating, VL very low confidence rating, BC balanced crystalloids, Iso-albumin iso-oncotic albumin, Hyper-albumin hyperoncotic albumin, 50-HES low molecular weight hydroxyethyl starch, H-HES loftier molecular weight hydroxyethyl starch

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Fig. 3
figure 3

Sequential network meta-analyses (SNMA) over sepsis patient bloodshed analysis amidst a balanced crystalloids versus saline, b balanced crystalloids versus depression molecular weight hydroxyethyl starch (Fifty-HES), c balanced crystalloids versus albumin, and d balanced crystalloids versus gelatin. Y-centrality represent the z scores for effect sizes, and green dots (trials) and dark-green line along the Ten-axis show the trend of cumulating evidence toward achieving maximal information. The bluish line represents the SNMA efficacy purlieus, and orange line represents the futility boundary. The greenish dots and green line showtime in the centre; when they pass the blue line, this indicates that a pregnant deviation in the outcome between the two treatments has been attained. When they laissez passer the orange line, this suggests no difference in the outcome betwixt the ii treatments. I iso-oncotic albumin, H hyperoncotic albumin

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Fig. iv
figure 4

Surface under the cumulative ranking curve area (SUCRA) for bloodshed, fluid resuscitation volume, astute kidney injury, and blood transfusion volume among sepsis, surgical, trauma, and traumatic encephalon injury patients. Dark color bar represents significantly better or worse interventions, and the differences between fluid types are shown to a higher place the bars

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Sepsis patients—fluid resuscitation volume

Thirteen trials with 10,970 participants reported usable results for fluid resuscitation volume in sepsis patients. Balanced crystalloids and saline required more fluid volume than iso-oncotic albumin with mean differences (MD) of 2122 mL (95% CI − 300 to 4544 mL) and 1964 mL (95% CI 89–3840 mL), respectively (Fig. 2b). SUCRA revealed that the colloids were associated with less resuscitation fluid volume than crystalloids (Fig. 4).

Sepsis patients—acute kidney injury

Eleven trials with x,569 participants reported usable results for acute kidney injury. Balanced crystalloids significantly reduced a greater risk of acute kidney injury than L-HES (OR, 0.80; 95% CI 0.65–0.99) and H-HES (OR, 0.54; 95% CI 0.37–0.84) (Fig. 2c). SUCRA ranking revealed that gelatin, balanced crystalloid, saline, and iso-oncotic albumin had a lower risk of acute kidney injury than 50-HES and H-HES (Fig. 4).

Sepsis patients—red blood cell transfusion book

Ten trials with 11,979 participants reported usable results for the packed crimson blood cell transfusion volume. Balanced crystalloids required less volume of red blood cell transfusion than hyperoncotic albumin (Md, 274 mL; 95% CI 5–548 mL), L-HES (Md, 232 mL; 95% CI 35–430 mL), and H-HES (Physician, 497 mL; 95% CI 141–854 mL). (Fig. 2d). SUCRA revealed that the crystalloids and iso-oncotic albumin were associated with less transfusion volume than other colloids (Fig. 4).

The funnel plot and Egger's exam did not detect any significant publication bias (Additional file i: appendix pp. 114–116). Loop inconsistency and pattern inconsistency were likewise not detected (Additional file 1: appendix pp. 124–129). The meta-regression did not alter the ranking lodge (Boosted file 1: appendix pp. 138–139). The evidence certainty in mortality revealed a moderate-to-loftier bear witness conviction in comparison, including balanced crystalloids, saline, and Fifty-HES; low-to-moderate in iso-oncotic albumin and hyperoncotic albumin; and very low in gelatin and H-HES (Additional file one: appendix pp. 139–142). Results of sensitivity analyses with the exclusion of the largest SMART trials [12] or the inclusion of the pilot Common salt trial [25] in Additional file 1: appendix 14 prove no substantial differences from the main assay.

Surgical patients

From 1979 to 2020, eight (34.lxxx%), 6 (26.00%), 6 (26.00%), and 3RCTs compared different resuscitation fluids in patients receiving cardiac surgery, aortic surgery, major abdominal surgery, and hip arthroplasty and cystectomy, respectively (Additional file 1: appendix pp. 32–36). Fluid resuscitation was provided during surgical procedures to maintain hemodynamic parameters in most trials, and the mean resuscitated fluid of involvement was 3327.5 mL (Additional file 1: appendix 65–67).

Surgical patients—mortality

Twenty-three trials with 4646 participants had valid results on bloodshed. There were no significant differences in mortality between 7 interventions (Fig. 5); SUCRA showed that hyperoncotic albumin and balanced crystalloid were associated with less mortality than gelatin, HES, and saline (Fig. 4).

Fig. 5
figure 5

Network geometry and woods plot in surgical patients with four outcomes. a Mortality, b fluid resuscitation amount, c astute kidney injury, d transfusion corporeality. The divergence amongst each comparison is visualized with woods plot, and the effect size and evidence rating are labeled on the right-hand side. The bold characters are to emphasize significant contrasts. The 95% confidence intervals in the forest plot are clipped to arrows, when they exceed the limit of x-centrality. OR odds ratio; *p < 0.05; **p < 0.01; H high confidence rating, Chiliad moderate confident rating, Fifty low conviction rating, VL very low conviction rating, BC counterbalanced crystalloids, Iso-albumin iso-oncotic albumin, Hyper-albumin hyperoncotic albumin, 50-HES depression molecular weight hydroxyethyl starch, H-HES high molecular weight hydroxyethyl starch

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Surgical patients—fluid resuscitation volume

20 trials with 4512 participants provided data on resuscitation fluid book. Balanced crystalloids group required significantly more fluid resuscitation volume than iso-tonic albumin (MD, 2612 mL; 95% CI 1416–3800), hypertonic albumin (MD, 2852 mL; 95% CI 742–4962), 50-HES (Medico 1494 mL; 95% CI 345–2644), H-HES (Medico, 1462 mL; 95% CI 418–2505), and gelatin (Doctor, 1154 mL; 95% CI 64–2240) (Fig. five). SUCRA ranking showed that colloids (albumin, HES, and and then gelatin) were associated with less fluid resuscitation volume than crystalloids (Fig. 4).

Surgical patients—acute kidney injury

14 trials with 4248 participants reported results for acute kidney injury. The ORs betwixt 7 treatments were not statistically significant (Fig. 5). SUCRA showed iso-oncotic albumin, and counterbalanced crystalloids were associated with less acute kidney injury than HES and gelatin.

Surgical patients—cherry blood prison cell transfusion book

Sixteen trials with 2818 participants presented usable results for red blood cell transfusion volume. Ranking probabilities showed that albumin, L-HES, and then gelatin were associated with less transfusion volume than H-HES and crystalloids (Fig. v).

Publication bias and inconsistency were not significant (Additional file 1: appendix pp. 118–121). The confidence ratings were low to very low among all comparisons in surgical trials (Additional file 1: appendix pp. 143–146).

Trauma and traumatic brain injury patients

From 1977 to 2018, 10 RCTs compared different resuscitation fluids in trauma patients who required fluid resuscitations, and 4 RCTs in traumatic brain injury patients. (Boosted file 1: appendix pp. 37–39). Patients' mean age was 48.6 years, predominantly male (69.8%), and mean resuscitation written report fluid was 5481 mL amongst trauma trials. (Additional file 1: appendix pp. 82–86).

10 trials with 5076 participants had valid results on mortality in trauma patients, and differences in bloodshed were not significant betwixt interventions in trauma patients. Balanced crystalloid required less volume of crimson claret cell transfusion than saline (Medico, 350 mL; 95% CI 160 mL to 540 mL) and Fifty-HES (Physician, 964 mL; 95% CI 400 mL to 1527 mL). Four trials with 1970 participants had valid results on bloodshed in traumatic encephalon injury patients, and saline reduced mortality than albumin with OR of 0.55 (95% CI 0.35–0.87) (Additional file 1: appendix pp. 103–114). The conviction ratings were depression to very low among all comparisons in traumatic and traumatic brain injury trials (Additional file 1: appendix pp. 123–124, 128, 148–150).

Discussion

To our knowledge, this assay is the largest NMA in the field of fluid resuscitation, every bit nosotros considered a larger number of outcomes and undertook carve up analyses for patients with different conditions. In sepsis patients, balanced crystalloids and iso-oncotic albumin were associated with lower mortality rates, lower risks of acute kidney injury, and less cherry blood cell transfusion book. In surgical patients, nonsignificant differences in the risks of mortality and acute kidney injury were observed between the seven interventions, but counterbalanced crystalloids required the greatest volume of fluid resuscitation among all fluid types. In traumatic brain injury trials, iso-oncotic albumin was associated with college mortality than saline.

Previous studies and important differences from this study

In many previous meta-analyses on fluid resuscitation, sepsis, surgical, trauma, and traumatic brain injury patients were put together as a single group. In 2013, Perel et al. published a meta-analysis [26] of critically ill patients of all causes, and some other meta-assay on HES [27], including patients with different causes existence grouped together. Our analyses separated patients' conditions, thereby providing more than precise information applied to specific subgroups of patients. Furthermore, previous meta-analyses also combined different fluid types into a single treatment. Our network meta-analysis used a more than comprehensive classification of resuscitation fluids according to the current knowledge, yielding more clinically meaningful information.

Crystalloids: balanced crystalloids and saline

Several meta-analyses and current sepsis guideline recommended that crystalloids are the fluid of pick for resuscitation [26, 28]. The nowadays study found that among crystalloids, counterbalanced crystalloids bear witness better survival do good and renal function for sepsis and surgical patients than saline does, and the reverse was found in traumatic brain injury patients. Instead of because crystalloids as one treatment grouping, we could be more specific in considering balanced crystalloids for sepsis and surgical patients, and saline for traumatic brain injury patients. Even so, both crystalloids required a higher book to achieve resuscitation goals. Therefore, in add-on to evaluate fluid responsiveness with passive leg raising or other static tests continuously, choosing optimal fluid types could also prevent fluid overload. [29].

Albumin: iso-oncotic and hyperoncotic albumin

The osmotic pressure in iso-oncotic solution was similar to plasma, and hyperoncotic solution was higher than plasma. Iso-oncotic albumin was designed for fluid resuscitation and has volume-sparing effect; hyperoncotic albumin was used to maintain target serum albumin concentration, which helps to maintain effective book by recruiting endogenous fluideleven. This study plant that iso-oncotic albumin was associated with better survival benefit in sepsis patients who suffer hypovolemia due to extravascular fluid loss acquired past increased vascular permeability. However, hyperoncotic albumin achieved better survival possibilities in surgical patients, whose blood loss was caused by uncorrected blood loss. This indicated that iso-oncotic albumin helps with providing more volume for sepsis resuscitation, while hyperoncotic albumin is more beneficial for uncorrected claret loss patients with normal vascular permeability. Likewise, iso-oncotic albumin in hypotonic solution was associated with higher mortality rate in traumatic brain injury patients, and greater fluid volume and hypotonic solution may further enhance intracranial pressure, leading to a higher mortality [thirty].

Hydroxyethyl starch (HES): L-HES and H-HES

HES of college molecular weight has been retracted from the market, but the HES of lower molecular weight is still in use in daily practice, especially in surgical or trauma patients. Even so, this study found that L-HES was associated with the highest mortality rate in sepsis, surgical, and trauma patients, and a greater take a chance of acute kidney injury and greater transfusion volume was required during the resuscitation menstruation. However, for traumatic encephalon injury patients, Fifty-HES and saline, both hypertonic solutions, were associated with better survival than hypotonic solution, including iso-oncotic albumin and balanced crystalloid.

Gelatin

Many review articles are opposed to gelatin employ for fluid resuscitation due to the risk of anaphylaxis and astute kidney injury, only those opinions were based on creature studies, case series, or RCTs designed for other purposes [xi, 31, 32]. Recent large RCTs reveal conflicting results, in that gelatin is associated with a nonsignificant, lower mortality than balanced crystalloids and salinethree. Our sequential NMA demonstrated that the z-score trend for the difference between counterbalanced crystalloids and gelatin has not yet exceeded the efficacy or futility boundary, indicating that the testify was notwithstanding insufficient (Fig. ii).

Strengths and limitations

The nowadays NMA analyzed all outcomes from previous RCTs, specially on the fluid resuscitation volume, which has never been considered in previous meta-analyses. This report likewise analyzed seven fluid types and patients' conditions separately and demonstrated that the benefit or harmful furnishings of the fluid types were largely dependent on patients' conditions. We present results from NMA followed by those from sequential NMA, in which the dynamic updates of the effect size aid to corroborate the NMA results and estimate prove doubtfulness past depicting the trend and making allowance for multiple testing. Our NMA too has some limitations: beginning, in sepsis trials (sample size [n] = 14,659), the testify was adequate between balanced crystalloids and saline, L-HES, and albumin, but insufficient between balanced crystalloids and gelatin. The confidence rating was depression in surgical (n = 3871) and traumatic trials (n = 5076) because the sample size was bereft and confidence intervals were wide. The conviction rating was very low for traumatic brain injury trials (northward = 1970) considering the direct and indirect evidence was inconsistent and sample sizes were insufficient. Secondly, the benefit or harm of gelatin could not be determined from the current evidence. Acute kidney injury was ranked all-time for gelatin in sepsis patients (only one trial) merely was worse in surgical patients (simply 2 trials). Survival benefit was also inconsistent betwixt sepsis and surgical patients (Table 1). Equally very few trials included gelatin, the prove on gelatin should exist interpreted with cautions. Third, blood transfusion thresholds are unclear and largely dependent on physician decision in the included trials. In Boosted file 1: appendix viii.1.5 (appendix pp. 74–75), we listed the claret transfusion volume and number of bleeding events requiring transfusion. Finally, the amount of investigation fluid was often very express in many trials, and large volumes of these resuscitation fluids have not been well investigated. Some undetected adverse events may occur if larger volumes are used.

Table 1 Characteristics of the fluids assessed and qualitative summary from this network meta-assay

Total size table

Conclusions

Amongst sepsis and surgical patients, balanced crystalloids and albumin attained lower mortality rates, lower risks of acute kidney injury, and less red blood transfusion volume than did saline and L-HES. Balanced crystalloids required the greatest fluid resuscitation volume than all the other fluid types. In traumatic encephalon injury patients, saline and L-HES showed better mortality rates than hypotonic solutions, including iso-oncotic albumin and balanced crystalloids.

Availability of data and materials

All data generated or analyzed during this written report are included in this published article and its supplementary files.

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Acknowledgements

Not applicable.

Funding

This work was partly funded by grants from the Ministry building of Science and Engineering science in Taiwan (grant no. MOST 106-2314-B-002-098-MY3 & MOST 109-2314-B-002-150-MY3).

Author data

Affiliations

  1. Institute of Epidemiology and Preventive Medicine, National Taiwan University, Room 539, No. 17, Xu-Zhou Rd., Taipei, 10055, Taiwan

    Chien-Hua Tseng, Ming-Chieh Shih & Yu-Kang Tu

  2. Segmentation of Pulmonary Medicine, Department of Internal Medicine, Schoolhouse of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Chien-Hua Tseng

  3. Division of Critical Intendance Medicine, Department of Emergency and Critical Care Medicine, Shuang Ho Hospital, Taipei Medical Academy, New Taipei City, Taiwan

    Chien-Hua Tseng

  4. Segmentation of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan

    Chien-Hua Tseng & Tzu-Tao Chen

  5. Sectionalization of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical Academy, New Taipei City, Taiwan

    Mei-Yi Wu

  6. Sectionalisation of Nephrology, Department of Internal Medicine, School of Medicine, Higher of Medicine, Taipei Medical Academy, Taipei, Taiwan

    Mei-Yi Wu

  7. Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

    Ming-Cheng Chan

  8. College of Science, Tunghai University, Taichung, Taiwan

    Ming-Cheng Chan

  9. Section of Dentistry, National Taiwan University Infirmary, National Taiwan University, Taipei, Taiwan

    Yu-Kang Tu

  10. Research Center of Big Information and Meta-Assay, Wan Fang Hospital, Taipei Medical Academy, Taipei, Taiwan

    Yu-Kang Tu

Contributions

CT and TT performed systemic reviews. CT, MY, and MC analyzed data and did the sequential network meta-analysis. TT, MY, and MC provided clinical aspects implications. CH and YK were major contributors in writing the manuscript. All authors read and approved the final manuscript.

Corresponding writer

Correspondence to Yu-Kang Tu.

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The authors declare that they take no competing interests.

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Tseng, CH., Chen, TT., Wu, MY. et al. Resuscitation fluid types in sepsis, surgical, and trauma patients: a systematic review and sequential network meta-analyses. Crit Intendance 24, 693 (2020). https://doi.org/10.1186/s13054-020-03419-y

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  • DOI : https://doi.org/10.1186/s13054-020-03419-y

Keywords

  • Fluid therapy
  • Intensive care
  • Resuscitation
  • Colloids
  • Crystalloids

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