In the present study, two senior physicians of the same ICU, with similar background, were sent to preside over ICU daily works of Jinniu Hospital affiliated to Sichuan Provincial Hospital. And the patients enrolled before application of point-of-care ultrasound were not significantly different from those enrolled after, in respect to principal diagnoses, disease severity on admission and age. These patients were comparable, except for the application of point-of-care ultrasound.
The present study showed that cumulative fluid balance during ICU stay was an independent risk factor of in-ICU mortality. After application of point-of care ultrasound, a dramatic change from positive fluid balance to negative one occurred. And the change in fluid balance was associated with a significant reduction in in-ICU mortality.
It was reasonable to direct fluid therapy with point-of-care ultrasound examination of internal jugular veins and inferior vena cava. Point-of-care ultrasound examination of internal jugular veins should not be viewed as a brand-new concept; distention of internal jugular veins had the same implications as distention of superficial neck veins. Point-of-care ultrasound examination of internal jugular veins was better than visual inspection of superficial neck veins, in that it could probe deeper. One major limitation of visual inspection was that jugular veins were not always observable, especially in obese patients. Distension and reduced collapsibility of inferior vena cava pointed to normo-/ hyper-volemia and were proved to be very beneficial in guiding fluid therapy.
Why cumulative fluid balance during ICU stay notably affected the outcome of critically ill patients? There were two reasons worth mentioning. First, some critically ill patients were hypervolemic from the very beginning of their hospitalization. Second, catabolism and disuse.
Previous studies showed that many critically ill patients were essentially hypervolemic. For example, in critically ill anemic patients, hypervolemia was common. “Plasma volume excess”, in addition to “hemoglobin deficiency”, often characterized anemia when plasma volume was measured. Plasma volume could increase by 70% in chronic severe anemia. In heart failure with preserved ejection fraction, expanded total blood volume together with true anemia was common[21, 22]. In volume overload decompensated chronic heart failure, plasma volume expansion dilution-related “anemia” predominated. Dilution in consequence of sodium and water retention was an important reason for development of anemia in chronic heart failure. In patients with chronic kidney disease, anemia was often complicated with fluid retention and overhydration, resulting in increased risk of cardiovascular morbidity and mortality and chronic kidney disease progression. Expansion of plasma volume and hemodilution were important features of anemia due to hemopoietic diseases, such as leukemia.
Most critically ill patients experienced a catabolic course which was not easily reversed by medication or nutritional support. Critically ill patients developed muscle atrophy rapidly, as a result of both anabolic resistance (reduced stimulation of muscle protein synthesis to a given dose of protein/amino acids) and enhanced skeletal muscle breakdown, or as a result of iatrogenic protein undernutrition, and preferentially affecting the lower limbs. Both catabolism and disuse in bedridden cases resulted in breakdown of proteins and reduction of dry body weight, leading to production of “endogenous water” and release of water from degraded proteins and fats. Fluid derived from catabolism and disuse should be removed to avoid volume overload and tissue edema.
In critically ill postoperative patients and patients with severe nutritional depletion, a dramatic change in body composition was observed. Reduction of body weight was accompanied by a marked increase in extracellular water (by 4.0-5.1 liters in 31–34 days) . Rapid and massive total protein loss was accompanied by retention of large amounts of fluids in critically ill patients with major traumatic injury or severe sepsis. Trauma patients had retained > 6L and sepsis patients > 12L of fluids, mainly in the extracellular compartment, by the time they were hemodynamically stable. And in elderly patients (> 60 years) the period of extracellular water expansion was markedly prolonged compared to younger patients (< 40 years).
Fluids in excessive amounts could have deleterious effects on several organ functions, including acute kidney injury and worsening respiratory function. The danger of volume overload was already noted in some critically ill patients, namely sepsis/septic shock patients[2–4]. The present study was in line with these studies, suggesting that conservative fluid strategy was superior to liberal one, and that fluid removal or de-resuscitation after hemodynamic stabilization should be put into practice.
The negative impact of positive cumulative fluid balance could not be overestimated. Many hypervolemic patients died when given diuretics. If fluid management could be improved, these cases would add to the difference in survival between cases enrolled before application of point-of-care ultrasound and those enrolled after. The diuresis of these deceased patients was not well titrated, in respect of timing and dosing of diuretic administration. Admittedly, the fluid balance was difficult to maintain in these critically ill patients. Studies conducted by nephrologists showed that shift of fluid between intravascular and extravascular compartments could be surprisingly rapid; plasma refill rate reached up to 20.1 ± 4.0 ml/min during hemodialysis[33–35]. When re-absorption far exceeded the rate of volume removal, a “well-controlled” pace of negative fluid balance would result in hemodynamic instability.
One main problem was that physicians had difficulty adapting to such a paradigm shift; fluid challenge and positive fluid balance were still the only solution when facing shock and lactic acidosis. The improvement in outcome would be greater if all physicians had abandoned fluid preference.
Another limitation of the present study was that 28-day or 90-day mortality was not recorded. However, the contribution of post-ICU treatment to 28-day or 90-day mortality was difficult to estimate, and physicians’ and surgeons’ fluid preferences would have major impact on these outcome measures.