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

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' conditions are conflicting. Whether the mortality benefit of balanced crystalloid than saline can be inferred from sepsis to other patient group is uncertain, and adverse effect profile is not comprehensive. This study aims to compare the survival benefits and adverse effects of seven fluid types with network meta-analysis in sepsis, surgical, trauma, and traumatic brain injury patients.

Methods: Searched databases (PubMed, EMBASE, and Cochrane CENTRAL) and reference lists of relevant articles occurred from inception until January 2020. Studies on critically ill 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 difference. Risk of Bias tool 2.0 was used to assess bias. Confidence in Network Meta-Analysis (CINeMA) web application was used to rate confidence in synthetic evidence.

Results: Fifty-eight trials (n = 26,351 patients) were identified. Seven fluid types were evaluated. Among patients with sepsis and surgery, balanced crystalloids and albumin achieved better survival, fewer acute kidney injury, and smaller blood transfusion volumes than saline and L-HES. In those with sepsis, balanced crystalloids significantly reduced mortality more than 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 volume among all fluid types, especially in trauma patients. In patients with traumatic brain injury, saline and L-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 balanced crystalloids and albumin decreased mortality more than L-HES and saline in sepsis patients; however, saline or L-HES was better than iso-oncotic albumin or balanced crystalloids in traumatic brain injury patients.

Trial registration: PROSPERO website, registration number: CRD42018115641).

Keywords: Colloids; Crystalloids; Fluid therapy; Intensive care; Resuscitation.

Fig. 1

Summary of evidence search and selection

Fig. 2

Network geometry and forest plot in sepsis patients with four outcomes. a Mortality, b fluid resuscitation amount, c acute kidney injury, d transfusion amount. The difference among each comparison is visualized with forest 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-axis. Abbreviations: OR odds ratio; *p < 0.0.5; **p < 0.01; H high confidence rating, M moderate confident rating, L low confidence rating, VL very low confidence rating, BC balanced crystalloids, Iso-albumin iso-oncotic albumin, Hyper-albumin hyperoncotic albumin, L-HES low molecular weight hydroxyethyl starch, H-HES high molecular weight hydroxyethyl starch

Fig. 3

Sequential network meta-analyses (SNMA) over sepsis patient mortality analysis among a balanced crystalloids versus saline, b balanced crystalloids versus low molecular weight hydroxyethyl starch (L-HES), c balanced crystalloids versus albumin, and d balanced crystalloids versus gelatin. Y-axis represent the z scores for effect sizes, and green dots (trials) and green line along the X-axis show the trend of cumulating evidence toward achieving maximal information. The blue line represents the SNMA efficacy boundary, and orange line represents the futility boundary. The green dots and green line start in the middle; when they pass the blue line, this indicates that a significant difference in the outcome between the two treatments has been attained. When they pass the orange line, this suggests no difference in the outcome between the two treatments. I iso-oncotic albumin, H hyperoncotic albumin

Fig. 4

Surface under the cumulative ranking curve area (SUCRA) for mortality, fluid resuscitation volume, acute kidney injury, and blood transfusion volume among sepsis, surgical, trauma, and traumatic brain injury patients. Dark color bar represents significantly better or worse interventions, and the differences between fluid types are shown above the bars

Fig. 5

Network geometry and forest plot in surgical patients with four outcomes. a Mortality, b fluid resuscitation amount, c acute kidney injury, d transfusion amount. The difference among each comparison is visualized with forest 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-axis. OR odds ratio; *p < 0.05; **p < 0.01; H high confidence rating, M moderate confident rating, L low confidence rating, VL very low confidence rating, BC balanced crystalloids, Iso-albumin iso-oncotic albumin, Hyper-albumin hyperoncotic albumin, L-HES low molecular weight hydroxyethyl starch, H-HES high molecular weight hydroxyethyl starch