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Guidelines recommend crystalloids for fluid resuscitation in sepsis/shock and switching to albumin in cases where crystalloids are insufficient. We evaluated hemodynamic response to crystalloids/colloids in critically ill adults.The primary research question was: “Are crystalloids sufficient for volume replacement in severe indications (intensive care unit [ICU]/critical illness)?” Randomized, controlled trials (RCTs) were identified using PubMed and EMBASE, and screened against predefined inclusion/exclusion criteria. Meta-analyses were performed on extracted data.Fifty-five RCTs (N=27,036 patients) were eligible. Central venous pressure was significantly lower with crystalloids than with albumin, hydroxyethyl starch (HES), or gelatin (all p<.001). Mean arterial pressure was significantly lower with crystalloids vs. albumin (mean difference [MD]: −3.5mmHg; p=.03) or gelatin (MD: −9.2mmHg; p=.02). Significantly higher volumes of crystalloids were administered vs. HES (MD: +1775mL); volume administered was numerically higher vs. albumin (MD: +1985mL). Compared with the albumin group, cardiac index was significantly lower in the crystalloid group (MD: −0.6L/min/m2, p<.001). All mortality and 90-day mortality were significantly lower for crystalloids compared with HES (relative risk 0.91; p=.009 and 0.9; p=.005, respectively).Crystalloids were less efficient than colloids at stabilizing resuscitation endpoints; guidance on when to switch is urgently required.Crystalloids are less effective than colloids at stabilizing hemodynamic endpoints.There is an urgent need for guidance on when to switch to colloids in the ICU.Higher volumes of crystalloids are required in the ICU, compared with colloids.