The optimal range of fluid administration in patients undergoing lung resection surgery has been a controversial topic in anesthesia. There are hazards at both ends of the spectrum: Liberal o verhydration can lead to fluid-induced lung injury, while conservative fluid-management strategies have a risk for organ ischemia.

According to a review of the recent literature, however, researchers may be closer to establishing “safe” fluid limits.

“The evidence has shown that intraoperative fluid administration should be at a base rate of 1 to 2 mL/kg per hour plus replacement of blood losses,” said Jens Lohser, MD, MSc, FRCPC, associate professor and head of thoracic anesthesia at the University of British Columbia, in Vancouver. “In addition, overall fluid administration of more than 6 mL/kg per hour intraoperatively and a 24-hour fluid balance in excess of 20 mL/kg should be avoided, as they have been associated with acute lung injury.” Dr. Lohser presented the findings at the Society of Cardiovascular Anesthesiologists 2016 annual meeting.

In view of the increased recognition of acute kidney injury (AKI) and its associated morbidity and mortality in other surgical settings, there has been significant concern that fluid restriction will result in harm. “At this point, however,” Dr. Lohser added, “there is no evidence that this level of fluid restriction causes acute kidney injury in lung resection patients.”
Where Is the ‘Sweet Spot’?

As Dr. Lohser explained, many studies have been conducted on acute lung injury, with fluid repeatedly shown to be a risk factor. The pathophysiologic cause of lung injury is thought to be the disruption of the endothelial surface layer by multiple fluid-dependent mechanisms (Anesth Analg 2015;121:302-318).

“We’ve come a long way since post–lung resection lung injury was first described in 1984,” said Dr. Lohser. “We now realize that there are a vast number of factors that affect the ventilated lung and the collapsed lung. … What hasn’t changed is that acute lung injury remains the leading cause of death post–lung resection.”

The risks do not only follow lung resection. According to a recent paper, the most severe form of primary graft dysfunction after lung transplantation is directly related to the amount of fluid administered during the lung transplantation (Anesth Analg 2016;122:1081-1088).

Moreover, not only is fluid restriction important in the prevention of lung injury, it similarly speeds the recovery from established lung injury, according to Dr. Lohser.

A randomized controlled trial of patients admitted to the ICU with acute lung injury showed that restrictive fluid therapy led to earlier resolution of the lung injury, and importantly, no increase in other organ dysfunction (N Engl J Med 2006;354:2564-2575).

As Dr. Lohser explained, empirical data seem to suggest an optimal range of fluid administration, above which anesthesiologists must worry about overhydration and lung injury and below which organ ischemia can occur. Regarding the upper limit, said Dr. Lohser, there are a multitude of studies, but most of these are retrospective, with many yielding “very confusing” results. “It’s very hard to make sense of the numbers,” he noted. “Unfortunately, there are no good prospective data for lung resection.”

One of the best retrospective studies, an observational cohort of 879 lung resection patients in Geneva, found a 4.2% incidence of acute lung injury, with multiple risk factors, including fluid (Crit Care 2009;12:R41). Secondary analysis showed a clear odds ratio of 2.9 for increased fluid related to lung injury, said Dr. Lohser, who also noted that a follow-up study showed protective ventilation to be effective in minimizing acute lung injury (Curr Opin Anaesthesiol 2009;22:61-67).

“The researchers were able to show that with protective ventilation, the rate of acute lung injury decreased to 0.9%, which has to be considered the gold standard that’s been published to this point,” said Dr. Lohser, who reported that these patients received an average of 5.8 mL/kg per hour of fluid during lung resection surgery.
Fluid Restriction and AKI

On the other end of the spectrum, fluid restriction raises the “specter of organ malperfusion,” Dr. Lohser pointed out.

“There’s significant concern that if we fluid-restrict our patients, we’re going to cause organ malperfusion,” he said, “particularly acute kidney injury. As cardiac anesthesiologists, we’re well aware of the fact that acute kidney injury is more than just a perioperative bump in creatinine, but causes significant morbidity and mortality.”

The definitive study so far, a retrospective analysis of 1,442 patients undergoing thoracic surgery, found a 5.1% incidence of AKI (Anesth Analg 2016;122:186-193). However, as Dr. Lohser reported, a subgroup analysis looking at patients who received either less than 3 mL/kg per hour per surgery or more than this showed no relationship to AKI, despite the “rather restrictive” volume.

“If anything,” said Dr. Lohser, “the patients that received less than 3 mL/kg per hour had lower rates of acute kidney injury, although not to a statistically significant degree.”

Finally, a prospective study of 139 patients who underwent anatomic lung resections found increased pulmonary complications at a fluid threshold of 6 mL/kg per hour, similar to the Geneva study (J Thoracic Cardiovasc Surg 2015;149:314-321). On the low end of fluid delivery, an inflection point appeared somewhere in the 2- to 3-mL/kg per hour range, the researchers noted.

“We know for certain that fluid causes acute lung injury and the risk increases significantly somewhere above 6 mL/kg per hour,” said Dr. Lohser.

“At this point, however, there’s no compelling evidence that fluid restriction per se causes acute kidney injury, if hypoperfusion is avoided.

“Clearly, if you over-restrict your patient, there will be organ dysfunction at some point, but rates of 2 to 3 mL/kg per hour have not been shown to be associated with acute kidney injury in lung resection patients,” Dr. Lohser concluded.

—Chase Doyle

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