Supplement 16:Should We Keep Fluid Balance Neutral Or Even Negative Among ICU Patients?

Supplement 16:Should We Keep Fluid Balance Neutral or Even Negative Among ICU Patients?

After correction of the initial resuscitation phase of potentially inadequate filling associated with distributive or septic shock, an increased fluid balance has been associated with third spacing and organ dysfunction in animal models [[1]]. However, it remains largely unknown whether strategies that target a neutral or even negative fluid balance after this initial resuscitative phase may be linked with improved clinical outcomes in humans.

Evidence Summary:

A systematic review identified 10 RCTs and 32 observational studies of relevance [[1]]. Based on the combined results of 13 studies, non-survivors were found to have a more positive fluid balance on ICU day 7 as compared to survivors (7737.9 mL versus 3109.9) [[1]]. Moreover, data from 23 studies suggested that mortality was reduced using deliberate attempts at conservative fluid management (OR 0.38 [95% CI 0.28 to 0.53]) as compared to non-conservative fluid management [[1]]. Although these results are interesting, they are limited by indirectness and risk of bias given the inclusion of varying study designs and patient populations and use of many different interventions.

Recommendation:

The WSACS SUGGESTS using a protocol to try to avoid a positive cumulative fluid balance in the critically ill with, or at risk of, IAH, after the acute resuscitation has been completed and the inciting issues/source control have been addressed (Management Suggestion 4; GRADE 2C).

Rationale:

Critically ill patients who can be cared for without requiring massive fluid administration have consistently been reported to have better outcomes. However, current evidence is insufficient to attribute improved outcomes to negative fluid balance, and more research is needed.

Discussion

Fluid Management Strategies: Overview

Administering fluids to the critically ill/injured has long been a basic initial response among clinicians world-wide. This is potentially justified by the fact that the shock state necessitates an obligatory loss of fluid to the “third space”, and this hassaved numerous lives and significantly reduced the risk of renalfailure as a complication of burn injury[2-4]. However it has been frequently observed that excessive resuscitation with crystalloid fluids may be contribute to an increased incidence ofACS[5-8]. Indeed, positive fluid balance resulting from third spacing is independently associated with impaired organ function and worse outcome[9-12]. Conversely, achievement of negative fluid balance restrospectively predicts survival associates with improved lung function[13, 14]. Thus, the overall topic of fluid management strategies was considered as an overarching concept, followed by individual considerations of the types of fluids, and thereafter potential modalities to modify body fluid’s such as diuertic therapy and renal replacement therapies.

Fluid Therapy:

Narrative

This question was formulated as: does a management strategy attempting to obtain fluid balance in equilibrium or even negative (conservative fluid strategy) after day 3 result in a lower IAP and improved patients outcomes compared to management strategies that either accept a liberal fluid management and will the latter result in higher IAPs in critically ill adults in critical care units?

Evidence Summary

Systematic review identified 40 relevant citations, includingone meta-analysis (published in abstract form), 10 RCTs, 7 interventional studies, 28 observational studies, and 4 case series, which examined a total of 23625 critically ill patients.In 23 studies, IAP was measured. A Summary of Studies is available online at Supplement A4 Best Evidence Profile Conservative Fluid Management in Critically Ill.

Fluid balance and survivorship

A meta-analytic aproach was utilized analyzing the best available data abstracted from 7 uncontrolled prospective cohort studies[12, 15-20], 2 uncontrolled retrospective cohort studies[13, 21], 2 retrospective non-randomized controlled cohort studies[22, 23], and a retrospective review[24] of a randomized trial of a separate intervention[24, 25] that considered fluid balance in relation to survival in critical illness. When compiled, the data from a total of 3246 patients enrolled in these 13 studies[13]revealed that non-survivorship (n= 1643, mortality being 50.6%) was asociated with a more positive cumulative fluid balance by day 7 of their ICU stay. The cumulative FB was on average 4628 ml more positive in non-survivors compared to survivors. The collated findings of these studies is presented at Supplement A5 - Fluid balance and survivorship.

Management approach to fluid management and mortality: Does outcome asociate with reduced fluid balance.

The compiled data from 12871 patients enrolled in 23[5, 12-16, 19, 21-37] studies involving critically ill and peri-operative patients showed that outcome was significantly improved when associated with a conservative fluid regimen (OR 0.34). This is illustrated in the Forest plot at Supplement A6 - Forest plot looking at the effect of a restrictive fluid regimen on mortality. In patients treated with a restrictive fluid regimen the associated mortality decreased from 29.1% (1859 deaths in 6384 patients) to 22.2% (1443 deaths in 6488 patients)(p<0.0001). Actual data on cumulative FB was available in 6555 patients from 13 studies: overall conservative treatment was associated with a less positive FB and the cumulative FB was on average 5470 ml less positive after 1 week of ICU stay. The summary of findings of these studies and Forrest plots are given at Supplement A6 - Forest plot looking at the effect of a restrictive fluid regimen on mortality.

Do patients with IAH have a more positive fluid balance?

Data was available from 1517 patients recovered from 8 cohort or case-controlled studies[16, 18, 20, 22, 38-40]. Meta-analyzing the pooled results revealed that the 597 patients with IAH (incidence being 39.4%) had a more positive fluid balance than those without IAH. The cumulative FB after 1 week of ICU stay was on average 3389 ml more positive. The Forrest plot and graphical detail are given at A7- Cumulative Fluid Balance after 1st ICU Week.

Does IAP improve with interventions acting on lowering FB?

Only 10 studies looked at the effects of net fluid removal strategies (use of furosemide or renal replacement therapy with net ultrafiltration) on IAP. These were case studies or small series. An overall total fluid removal of 6810 ml was associated with a drecrease in IAP from 21.5 to 12 mmHg. A dose related effect was observed: the more negative the fluid balance the greater the decrease in IAP. The summary of findings and Forrest plots are given at Supplement A8 - Cumulative fluid balance and intra-abdominal hypertension

Recommendation

The WSACS SUGGESTS using a protocol to try to avoid a positive cumulative fluid balance in the critically ill with, or at risk of IAH, after the acute resuscitation has been completed and the inciting issues/source control have been addressed (Management Suggestion Recommendation 4; GRADE 2C).

Rationale

Consistently in critical care, patients who can be cared for without requiring massive fluid administration have better outcomes. The overall evidence to date eflects association rather than causality however and much of the outcome data was surrogate in nature. On a practical basis at the bedside, this may be interpretted as atempting to obtain a zero to negative FB by day 3 in those who have been resuscitated to hemodynamic stability and to keep the cumulative FB on day 7 as low as possible.

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