Less is More: Optimising Fluid Therapy

Introduction

Intravenous fluids are among the most widely used medications prescribed in the acute care setting. Fluids are prescribed for the resuscitation of patients in circulatory shock, maintenance of fluid and electrolyte balance, replacement of ongoing losses, as diluents for medications, and as flushing solutions. However, not uncommonly, fluids are administered without any clear indication, overlooking their potential harms. Some of the harmful consequences of fluid prescriptions include fluid overload, damage to the endothelial glycocalyx, tissue oedema, organ dysfunction, electrolyte imbalances, metabolic acidosis, and hypothermia.1 In this brief review, we will discuss proven strategies aimed at maximising the benefits and minimising the harms of intravenous fluid prescriptions. These strategies will be discussed in the context of a typical intensive care unit (ICU) patient with septic shock, though they can be extrapolated to other clinical scenarios as well.

Stages of Fluid Therapy

Rescue Phase

Minimise initial resuscitation volume: The Surviving Sepsis Campaign guidelines suggest infusing 30 ml/Kg over 3-hours for every patient with septic shock.6 However, this recommendation is based on limited evidence. A potentially better strategy would be to individualise initial fluid volume based on the clinical response. One way is to follow the original description of intravenous fluid therapy by Sir Thomas Latta ‘‘...having no precedence to guide me I injected ounce after ounce of fluid closely observing the patient.’’7 Based on pharmacokinetic data, the minimum volume of fluid to be administered should be 4 ml/Kg.8

Early initiation of norepinephrine
In patients with vasodilatory or distributive shock, early initiation of vasopressor, especially norepinephrine, has got several beneficial effects:

• Early reversal of life-threatening hypotension
• Reduction in the duration of hypotension9
• Increase in cardiac output10
• Increased mean systemic filling pressure and
venous return
• Improved coronary perfusion
• Effect of norepinephrine on the beta-1 receptor
• Potential reduction in cumulative fluid balance11
• Earlier reversal of shock12

Norepinephrine infusion should be initiated if the patient meets any of the following criteria:

1. Low diastolic blood pressure (DBP): The aim is to restore coronary perfusion rapidly. In patients with postpartum haemorrhage, troponin rise was observed with DBP less than 50 mmHg.
2. Extreme vasodilatation: A very wide pulse pressure reflects extreme vasodilatation. In patients with septic shock, Diastolic Shock Index >2.3 is suggestive of vasodilatation and could be a trigger for starting norepinephrine infusion (Diastolic Shock Index = Heart rate/ Diastolic blood pressure).13,14
3. After 1-2 Litres of IV fluid: This approach has been shown to reduce cumulative fluid balance.11

Optimisation Phase

Monitored fluid boluses: Patient should be -carefully accessed for fluid responsiveness and fluid tolerance before administering further fluid bolus. A fluid bolus is expected to improve tissue perfusion by increasing venous return and cardiac output by at least 10%-15%. However, only half of the critically ill patients exhibit this increase in cardiac output following fluid bolus administration.15 In the remaining half, fluid boluses contribute only to fluid overload and worsening organ dysfunction. Several bedside manoeuvres have been developed to increase the preload status of the left side of the heart by utilising heartlung interaction or shifting body fluids from the lower body compartment. These manoeuvres help clinicians identify patients whose cardiac output may improve following an actual fluid bolus.2 These tests of fluid responsiveness can potentially prevent unnecessary fluid bolus administration in fluid-unresponsive patients.

However, identifying fluid responsiveness alone does not ensure that fluid bolus administration will not produce venous congestion. A dynamic assessment of tissue oedema and the patient's capacity to tolerate additional fluids without causing organ-damaging venous congestion is necessary. Fluid tolerance refers to evaluating a patient's ability to handle further fluid administration without worsening venous congestion, tissue oedema, and organ dysfunction.16,17 Studies have shown that fluid intolerance or venous congestion may occur in both fluidresponsive and non-responsive patients.18

Figure 2 provides a schematic diagram to decide about the need for fluid boluses in the optimisation phase

Figure 2: A decision tree for fluid management based on perfusion status, fluid responsiveness, and fluid tolerance.

Hyperoncotic albumin: Unlike hypo-oncotic or iso-oncotic albumin (4%-5%), volume expansion with hyper-oncotic albumin (20%-25%) corresponds with twice the infused volume, both in healthy volunteers and in patients with septic shock.19,20 This volume sparing effect of hyperoncotic albumin is further confirmed by two recent randomised control trials.21,22 Hyperoncotic albumin may be considered a preferred fluid option in the optimisation phase, particularly when crystalloid volume exceeds significantly. However, patient-centered outcomes and cost-benefit ratios of hyperoncotic albumin boluses need to be confirmed in larger studies.

Resuscitation target: Target for resuscitation should be selected carefully for an individual patient. In the ANDROMEDA SHOCK study, patients resuscitated by targeting capillary refill time (CRT) had lower cumulative resuscitation volume than those resuscitated using the same protocol but guided by lactate.23 Kinetics of lactate clearance is much slower compared to CRT.

Stabilisation Phase

Maintenance fluid: In ICU patients, one-third of total fluid intake consists of maintenance fluid, significantly contributing to volume overload.24 Prescription of maintenance fluid should be strictly limited to patients who cannot receive fluids via oral or enteral route. The choice of maintenance fluid can also have an impact on sodium levels and fluid overload. In the TOPMAST study, prescription of isotonic maintenance fluid (Na 154 mmol/L) had a more positive fluid balance and higher rates of clinical fluid overload than those receiving hypotonic maintenance fluid (Na 54 mmol/L).25

Evacuation Phase

De-resuscitation: Patients should be carefully monitored for signs of venous congestion and fluid overload:

• High left or right sided filling pressure(s): Elevated CVP (central venous pressure) is associated with both mortality and acute kidney injury (AKI).26 Echocardiographic measurement of E/e' ratio can be taken as a surrogate of pulmonary artery occlusion pressure.
• Evidence of pulmonary congestion: Examples include extravascular lung water index (EVLWI) or B-profile.27
• Signs of right sided venous congestion: Examples include portal pulsatility index, renal venous impedance index, VEXUS.28,29

Diuresis (or ultrafiltration for patients on renal replacement therapy) should be considered, if venous congestion and volume overload are evident. However, diuresis should not be initiated if there is ongoing resuscitation or evidence of tissue hypoperfusion.

• Simultaneous infusion of 20%-25% albumin can potentiate fluid removal.30
• Low-dose vasopressor infusion can potentially help in redistributing blood volume from interstitial to intravascular compartment.31
• Hypotension is a potential risk during de-resuscitation. The risk of hypotension is significantly higher in patients with evidence of “fluid responsiveness” before initiating diuresis or ultrafiltration. Accessing fluid responsiveness can help predict the safety of fluid removal in a well-perfused patient.32 Simultaneous infusion of 20%-25% albumin may help prevent hypotension.33
• haemodynamic instability (examples include hypotension, rapid fall in cardiac output, prolonged CRT, or worsening lactate levels). De-resuscitation measures should be halted if there is evidence of tissue hypoperfusion and haemodynamic instability