MIAMI BEACH – A failure to develop hypophosphatemia during the first few days after major hepatectomy was associated with up to a threefold increase in the risk of major complications, hepatic insufficiency, and 30-day mortality.
Contrary to a widely held belief, hypophosphatemia may not be a problem requiring treatment, but rather a normal physiologic response to liver resection – a sign that hepatocytes are working hard to regenerate and recover their function, Dr. Malcolm Squires said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.
"The process of liver regeneration is metabolically demanding," said Dr. Squires of Emory University, Atlanta. "Immediately after hepatectomy, the [adenosine triphosphate] content decreases by 35%. The level starts to recover by day 6, to about preoperative levels by day 14. But during that process, the hepatocytes are rapidly consuming ATP; there is a significant concurrent phosphate uptake by the liver remnant, and we see that decrease in serum phosphorus."
These are all signs of normal liver remnant recovery, Dr. Squires said. Consequently, the failure to follow this pathway suggests that the remnant is not on a good recovery trajectory, but instead, a path that could lead to big problems.
To examine this idea, he and his colleagues looked at 719 patients who had undergone major hepatectomy from 2000 to 2012 and who had serum phosphorus evaluated after surgery.
Measures included daily phosphorus levels for the first week after surgery, as well as the day of the phosphorus nadir. Mean age of the patients was 57 years. The most common type of resection was a right hepatectomy (39%), followed by a left (23%), extended right (20%), and extended left (6%). Ten percent of patients had a nonanatomic resection, and 20% a concurrent bile duct resection.
The most common pathology was metastatic colorectal cancer (32%), followed by cholangiocarcinoma (12%), hepatocellular carcinoma (9%), and metastatic neuroendocrine tumor (5%). Other pathologies made up the remainder.
Most patients (69%) got phosphorus repletion in the first 72 hours after surgery, although this intervention was not protocol driven, Dr. Squires noted.
Postoperative hepatic insufficiency developed in 63 patients (9%). About a fourth (169) had major complications. Mortality was 4% within 30 days and 5% within 90 days.
The median preoperative serum phosphorus level was 3.7 mg/dL. This fell precipitously to a median nadir of 2.4 mg/dL (the lower limit of normal), which occurred on postoperative day 2 or 3 for the majority of patients. Recovery was linear, with a near-complete postoperative recovery by day 14. Patients followed the same trajectory regardless of the type of hepatectomy.
The researchers dichotomized the patients into those with a postoperative day 2 phosphorus of 2.4 mg/dL or higher (72%), or below 2.4 mg/dL (28%).
Patients with the higher levels were significantly more likely to develop hepatic insufficiency (12% vs. 7%) and major complications (27% vs. 20%), and to die within 30 days (4% vs. 2%) and 90 days (8% vs. 4%).
A multivariate analysis found that phosphorus of more than 2.4 mg/dL increased the risk of hepatic insufficiency by 78% and major complications by 60%. It nearly tripled the risk of 30-day mortality (HR 2.7) and more than doubled the risk of 90-day mortality (HR 2.5).
The team also looked at the timing of phosphorus nadir. Most patients (80%) achieved this by postoperative day 3, so the researchers divided the group into those who had that level within 3 days and those who had it later. Patients with the delayed nadir were twice as likely to have hepatic insufficiency and major complications, and to die within 30 days. The trend was to increased death within 90 days as well, but Dr. Squires said the difference was not statistically significant.
Early postoperative phosphorus administration did not affect these findings, he added.
Dr. Squires reported having no financial disclosures.