Maintenance fluid therapy and fluid creep impose more significant fluid, sodium, and chloride burdens than resuscitation fluids in critically ill patients: a retrospective study in a tertiary mixed ICU population

We have taken a novel direction in the important field of intravenous fluid therapy in critically ill patients by looking beyond the fluids that are administered for resuscitation purposes. In our tertiary ICU, a long-standing awareness of the potential harm caused by fluid overload has led to a prescription strategy that involves the reduction of maintenance fluids as soon as nutrition can supply sufficient water and electrolytes. Yet, our real-life, extensive, granular dataset shows that, even in this setting, maintenance solutions continue to occupy an important place in the daily volume, sodium, and chloride burdens. This is in sharp contrast to the amount of resuscitation fluids, the use of which declines rapidly within the first few days of admission. Our results are even more pronounced than those of two multicenter point-prevalence studies in which resuscitation fluids were defined even more strictly but included blood products [16, 17]. In our view, these findings challenge the dominance of resuscitation fluids in the ongoing fluid debate and call for a realignment of scientific interest.

Although it is difficult to judge the reasons for fluid therapy retrospectively, and sometimes large doses of non-resuscitation fluids will certainly have been necessary, it is plausible that—despite our ICU’s fluid policy—maintenance solutions may at times have been prescribed too liberally. We believe the main explanation for this is to be found in the underestimation of the enormous, poorly accounted for volume that patients receive through fluid creep. Originating from intravenous, oral, and enteral medication, concentrated electrolytes, and small volumes that keep intravenous lines open, fluid creep was responsible for a median volume of 645 mL, thereby exceeding all other fluid sources.

Besides fluid volume, an equally or even more important clinical issue is sodium overload [18‐20]. Despite our hypotonic maintenance policy, the total daily sodium administration of 131 ± 137 mmol far exceeded the guideline-recommended dose of 1 mmol/kg/day [15]. This was even without taking into account the unmeasured but—according to prior data—substantial sodium burden imposed by the 681 ± 580 mL of fluid creep due to countless medications, many of which were probably dissolved in NaCl 0.9% [17‐19]. Sodium administration in excess of normal dietary intake (recommended to be lower than 2.3 g or 100 mmol/day in a healthy diet) leads to fluid retention and weight gain, independent of disease, as was demonstrated recently in an experiment comparing isotonic to hypotonic maintenance fluids in healthy subjects [21]. There is ongoing debate—originating from pediatric literature—about the optimal tonicity of maintenance fluids. The main concern among opponents of a hypotonic strategy is the occurrence of hyponatremia [22‐26]. We are still awaiting data in adult populations, yet guidelines continue to recommend that maintenance solutions be hypotonic in adults and that sodium levels be monitored in at-risk patients [15, 27]. Regardless of the pediatric strategy chosen, inadvertent non-maintenance sources of sodium have also been demonstrated conclusively in critically ill children [28].

In recent years, much scientific attention has been paid to the potentially detrimental effects of chloride, and its unphysiological presence in NaCl 0.9% [8, 29‐31]. A significant decrease in acute kidney injury was reported following the adoption of a chloride-poor strategy in the ICU when compared to the previous, more chloride-tolerant approach [7]. To the surprise of many, these findings were not prospectively confirmed in the SPLIT trial comparing balanced and unbalanced resuscitation fluids [5]. Although various explanations have been suggested, we believe our results provide a missing piece of the puzzle. As a result of its focus on resuscitation fluids, much larger sources of chloride in the form of maintenance and replacement fluids—which could have augmented Yunos’s renal benefit—were overlooked during the trial. To substantiate this hypothesis, we tested differences in chloride administration by simulating an unbalanced resuscitation strategy and found an additional daily chloride burden due to the hypothetical use of NaCl 0.9% and unbalanced colloids that was of negligible clinical importance.

Chloride burden could be reduced far more easily by intervening in the prescription of maintenance fluids, especially by altering their tonicity. A poorly considered maintenance strategy using isotonic fluids such as NaCl 0.9% (chloride 154 mmol/L)—or even Hartmann’s (110 mmol/L) or PlasmaLyte^® (98 mmol/L)—could lead to a substantial and unnecessary chloride overload. Our simulation illustrates that the reduced chloride due to a hypotonic maintenance strategy would far outweigh any gains afforded by a balanced resuscitation/replacement strategy. A final, unintentional chloride source was found in fluid creep. Strikingly, more chloride was administered through chloride-containing electrolyte solutions (10 mmol/day), e.g., potassium chloride, than could be prevented by our balanced resuscitation policy (3 mmol/day). Although, again, the nature of our dataset did not allow us to calculate the amount of chloride unintentionally administered by dissolving medication in NaCl 0.9%, given the extensive fluid creep involved, this amount is also likely to be substantial [17, 18]. The use of saline is rarely mandatory as a solvent, so we would advise consulting with hospital pharmacists and using sodium and chloride-poor alternatives whenever possible [32].

Fluid overload is a difficult parameter to grasp clinically, let alone assess scientifically. It is therefore commonly substituted by a positive cumulative fluid balance, which was identified more than 10 years ago as a marker of poor outcome in septic patients, independent of the severity of illness [13]. Since then, a positive cumulative fluid balance has been associated with organ failure, abdominal hypertension, and prolonged perioperative recovery and hospital stay [33‐39]. Unlike resuscitation fluids, maintenance solutions are not expected to contribute significantly to disrupted fluid balance, as they are dosed to balance sensible and insensible losses. Our statistical model supports this assumption and shows that resuscitation fluids have a more important “per milliliter” impact on cumulative fluid balance in septic patients than do maintenance and replacement solutions. However, as a result of their large mean volumes and their poor adaptation to the large, overlooked volume caused by fluid creep, non-resuscitation fluids play a prominent role in this worrisome parameter. This is another reason their (over)use should not be regarded as trivial.

Our study has three main limitations. Most importantly, fluid therapy is known to vary not only from country to country, and from hospital to hospital, but also from physician to physician as a result of training, tradition, economic factors, and personal convictions. Judging the external validity of our findings could therefore be challenging. On the other hand, we believe that fluid therapy is taken seriously in our ICU and—while there is always room for improvement—we are convinced that our policy is at the restrictive end of the spectrum. Moreover, we know of numerous hospitals in which glucose-free balanced or unbalanced isotonic crystalloids are the first choice when it comes to maintenance fluids. Therefore, we believe that the situation in many institutions could be at least comparable to and frequently even in excess of what we have presented here. Second, to assess fluid-induced harm, we selected cumulative fluid balance as the outcome parameter of our statistical model. It must be acknowledged that a positive fluid balance cannot be viewed as an exclusively detrimental factor, as it could also reflect the correct treatment of an existing intracellular or extracellular fluid deficit. The nature of our dataset did not allow us to judge the appropriateness of the clinical decision to administer fluids retrospectively. Finally, in the current study we assumed that chloride’s potential harm lies in the total cumulative dose over the course of an ICU stay. This has not yet been fully established, however, and it is possible that high infusion rates might exert more harm than chloride loads built up slowly over time. On the other hand, the only study published to date that succeeded in reducing the chloride burden did so by reducing every source of chloride, and not resuscitation fluids alone [7]. It might also be important to distinguish the absolute chloride load from the relative increase of chloride compared to sodium level. Although balanced formulations are commercially available, many hypotonic maintenance solutions contain equal amounts of sodium and chloride and could therefore cause metabolic acidosis [40]. The latter phenomenon, however, was previously reported to be of minor clinical importance [9, 41].