Low Ionized Calcium Levels Predict Trauma Mortality, Transfusion Needs

BOSTON – Trauma patients with low levels of ionized calcium at admission were at increased risk for death and coagulopathies and were more likely to need massive transfusions, compared with patients with normal physiologic levels.

Among 694 consecutive trauma activations over an 18-month period, the death rate for patients with ionized calcium levels below 1.0 mmol/L was 21%, compared with 13% for patients with levels of 1.0 mmol/L or higher (P = .016), Dr. Ann P. O’Rourke, of the division of general surgery at the University of Wisconsin in Madison, said at the annual meeting of the American Association for the Surgery of Trauma.

Ionized calcium levels also remained an independent predictor for massive transfusion requirements (10 or more units of packed red blood cells over 24 hours) in a logistic regression analysis controlling for age, sex, coagulopathy, and severity of injury (odds ratio, 2.557; P = .0004).

“Metabolic and cellular derangements related to shock occur rapidly post injury. We need to continue to identify reliable and reproducible markers of outcome, and ionized calcium levels drawn prior to any resuscitative efforts may serve as a reasonable marker,” Dr. O’Rourke said.

Calcium is a ubiquitous component of the clotting cascade, and is necessary for platelet activation and thrombus formation, she noted.

“Hypocalcemia has been shown to be a common metabolic derangement in critically ill patients. It has been shown to be prevalent in patients who are septic, in patients who have complications related to musculoskeletal trauma, and in burn patients,” she said.

Previous studies have shown that low ionized calcium levels are associated with hypotension and predict mortality, she added.

To see whether, as they hypothesized, low levels of ionized calcium at admission could predict massive transfusion, Dr. O’Rourke and colleagues at the University of Tennessee Health Science Center in Memphis, where she served a trauma surgery fellowship, prospectively studied all 694 patients with trauma initially treated at the center over an 18-month period. Patients transferred from other centers were excluded.

They collected data on demographics, injury mechanism, vital signs, 24-hour transfusion requirements, and mortality, and compared outcomes using Wilcoxon rank-sum and chi-square tests.

They defined low calcium as a level of 1.0 mmol/L or less, according to Youden’s index, which determines optimal cut-points as the area on a receiver operating characteristic curve where the highest degrees of test sensitivity and specificity meet.

The patients had a mean age of 38 years, 77% were men, and 67% had blunt trauma injuries. The mean Glasgow Coma Scale (GCS) score was 12, and the mean Injury Severity Score (ISS) was 23.

In all, 291 patients had high levels of ionized calcium (1.0 mmol/L or greater) and 403 had low levels. The high and low groups were evenly matched by age, sex, injury mechanism, and lactate levels, but GCS scores were significantly higher in the high-calcium group (12 vs. 11, respectively; P = .020), whereas ISS was higher in the low-calcium group (17 vs. 23; P = .003). Base deficit, a measure of the severity of shock, was lower in the low-calcium patients (–4.7 vs. –2.9; P less than .0001).

In addition to the higher mortality among patients low in calcium, these patients had significantly higher levels of coagulopathy, as measured by a mean international normalized ratio (INR) of 1.46 on arrival in the trauma bay, compared with 1.19 for patients with high calcium levels. Massive transfusions were required in 29% of the patients with low levels of ionized calcium, compared with 12% of the group with high levels (P less than .0001).

A multivariable logistic regression analysis showed that low ionized calcium level was the only significant predictor of transfusion. Neither age, admission GCS, ISS, or coagulopathy significantly predicted transfusion requirements.

“Admission ionized calcium levels may facilitate rapid identification of patients requiring massive transfusion, allow us to have earlier preparation and administration of blood products, and may serve as a trigger to our blood bank to initiate our massive transfusion protocols,” Dr. O’Rourke said.

Dr. Matthew Rosengart, the invited discussant, noted that “for decades we have recognized that alterations in calcium, such as hypocalcemia, develop in our sickest of patients with prevalence upwards of 88% in the presence of severe sepsis. The elusive question is why.”

Further investigations should focus on determining how ionized calcium levels fit in with other scoring instruments that incorporate immediately available biochemical parameters, he said.

“How does this parameter, calcium, perform when other validated scores are incorporated into your model? Does it retain its association after more rigorous adjustment for case mix, including base deficit or lactate? Should ionized calcium complement or replace these instruments?” asked Dr. Rosengart, of the University of Pittsburgh Medical Center.

“I would say that any additional tool we can have to make something more predictive, so that our decision making is better, is useful,” Dr. O’Rourke replied.

The funding source for the study was not specified. The authors and Dr. Rosengart had no conflict of interest disclosures.

BOSTON – Trauma patients with low levels of ionized calcium at admission were at increased risk for death and coagulopathies and were more likely to need massive transfusions, compared with patients with normal physiologic levels.

Among 694 consecutive trauma activations over an 18-month period, the death rate for patients with ionized calcium levels below 1.0 mmol/L was 21%, compared with 13% for patients with levels of 1.0 mmol/L or higher (P = .016), Dr. Ann P. O’Rourke, of the division of general surgery at the University of Wisconsin in Madison, said at the annual meeting of the American Association for the Surgery of Trauma.

Ionized calcium levels also remained an independent predictor for massive transfusion requirements (10 or more units of packed red blood cells over 24 hours) in a logistic regression analysis controlling for age, sex, coagulopathy, and severity of injury (odds ratio, 2.557; P = .0004).

“Metabolic and cellular derangements related to shock occur rapidly post injury. We need to continue to identify reliable and reproducible markers of outcome, and ionized calcium levels drawn prior to any resuscitative efforts may serve as a reasonable marker,” Dr. O’Rourke said.

Calcium is a ubiquitous component of the clotting cascade, and is necessary for platelet activation and thrombus formation, she noted.

“Hypocalcemia has been shown to be a common metabolic derangement in critically ill patients. It has been shown to be prevalent in patients who are septic, in patients who have complications related to musculoskeletal trauma, and in burn patients,” she said.

Previous studies have shown that low ionized calcium levels are associated with hypotension and predict mortality, she added.

To see whether, as they hypothesized, low levels of ionized calcium at admission could predict massive transfusion, Dr. O’Rourke and colleagues at the University of Tennessee Health Science Center in Memphis, where she served a trauma surgery fellowship, prospectively studied all 694 patients with trauma initially treated at the center over an 18-month period. Patients transferred from other centers were excluded.

They collected data on demographics, injury mechanism, vital signs, 24-hour transfusion requirements, and mortality, and compared outcomes using Wilcoxon rank-sum and chi-square tests.

They defined low calcium as a level of 1.0 mmol/L or less, according to Youden’s index, which determines optimal cut-points as the area on a receiver operating characteristic curve where the highest degrees of test sensitivity and specificity meet.

The patients had a mean age of 38 years, 77% were men, and 67% had blunt trauma injuries. The mean Glasgow Coma Scale (GCS) score was 12, and the mean Injury Severity Score (ISS) was 23.

In all, 291 patients had high levels of ionized calcium (1.0 mmol/L or greater) and 403 had low levels. The high and low groups were evenly matched by age, sex, injury mechanism, and lactate levels, but GCS scores were significantly higher in the high-calcium group (12 vs. 11, respectively; P = .020), whereas ISS was higher in the low-calcium group (17 vs. 23; P = .003). Base deficit, a measure of the severity of shock, was lower in the low-calcium patients (–4.7 vs. –2.9; P less than .0001).

In addition to the higher mortality among patients low in calcium, these patients had significantly higher levels of coagulopathy, as measured by a mean international normalized ratio (INR) of 1.46 on arrival in the trauma bay, compared with 1.19 for patients with high calcium levels. Massive transfusions were required in 29% of the patients with low levels of ionized calcium, compared with 12% of the group with high levels (P less than .0001).

A multivariable logistic regression analysis showed that low ionized calcium level was the only significant predictor of transfusion. Neither age, admission GCS, ISS, or coagulopathy significantly predicted transfusion requirements.

“Admission ionized calcium levels may facilitate rapid identification of patients requiring massive transfusion, allow us to have earlier preparation and administration of blood products, and may serve as a trigger to our blood bank to initiate our massive transfusion protocols,” Dr. O’Rourke said.

Dr. Matthew Rosengart, the invited discussant, noted that “for decades we have recognized that alterations in calcium, such as hypocalcemia, develop in our sickest of patients with prevalence upwards of 88% in the presence of severe sepsis. The elusive question is why.”

Further investigations should focus on determining how ionized calcium levels fit in with other scoring instruments that incorporate immediately available biochemical parameters, he said.

“How does this parameter, calcium, perform when other validated scores are incorporated into your model? Does it retain its association after more rigorous adjustment for case mix, including base deficit or lactate? Should ionized calcium complement or replace these instruments?” asked Dr. Rosengart, of the University of Pittsburgh Medical Center.

“I would say that any additional tool we can have to make something more predictive, so that our decision making is better, is useful,” Dr. O’Rourke replied.

The funding source for the study was not specified. The authors and Dr. Rosengart had no conflict of interest disclosures.

BOSTON – Trauma patients with low levels of ionized calcium at admission were at increased risk for death and coagulopathies and were more likely to need massive transfusions, compared with patients with normal physiologic levels.

Among 694 consecutive trauma activations over an 18-month period, the death rate for patients with ionized calcium levels below 1.0 mmol/L was 21%, compared with 13% for patients with levels of 1.0 mmol/L or higher (P = .016), Dr. Ann P. O’Rourke, of the division of general surgery at the University of Wisconsin in Madison, said at the annual meeting of the American Association for the Surgery of Trauma.

Ionized calcium levels also remained an independent predictor for massive transfusion requirements (10 or more units of packed red blood cells over 24 hours) in a logistic regression analysis controlling for age, sex, coagulopathy, and severity of injury (odds ratio, 2.557; P = .0004).

“Metabolic and cellular derangements related to shock occur rapidly post injury. We need to continue to identify reliable and reproducible markers of outcome, and ionized calcium levels drawn prior to any resuscitative efforts may serve as a reasonable marker,” Dr. O’Rourke said.

Calcium is a ubiquitous component of the clotting cascade, and is necessary for platelet activation and thrombus formation, she noted.

“Hypocalcemia has been shown to be a common metabolic derangement in critically ill patients. It has been shown to be prevalent in patients who are septic, in patients who have complications related to musculoskeletal trauma, and in burn patients,” she said.

Previous studies have shown that low ionized calcium levels are associated with hypotension and predict mortality, she added.

To see whether, as they hypothesized, low levels of ionized calcium at admission could predict massive transfusion, Dr. O’Rourke and colleagues at the University of Tennessee Health Science Center in Memphis, where she served a trauma surgery fellowship, prospectively studied all 694 patients with trauma initially treated at the center over an 18-month period. Patients transferred from other centers were excluded.

They collected data on demographics, injury mechanism, vital signs, 24-hour transfusion requirements, and mortality, and compared outcomes using Wilcoxon rank-sum and chi-square tests.

They defined low calcium as a level of 1.0 mmol/L or less, according to Youden’s index, which determines optimal cut-points as the area on a receiver operating characteristic curve where the highest degrees of test sensitivity and specificity meet.

The patients had a mean age of 38 years, 77% were men, and 67% had blunt trauma injuries. The mean Glasgow Coma Scale (GCS) score was 12, and the mean Injury Severity Score (ISS) was 23.

In all, 291 patients had high levels of ionized calcium (1.0 mmol/L or greater) and 403 had low levels. The high and low groups were evenly matched by age, sex, injury mechanism, and lactate levels, but GCS scores were significantly higher in the high-calcium group (12 vs. 11, respectively; P = .020), whereas ISS was higher in the low-calcium group (17 vs. 23; P = .003). Base deficit, a measure of the severity of shock, was lower in the low-calcium patients (–4.7 vs. –2.9; P less than .0001).

In addition to the higher mortality among patients low in calcium, these patients had significantly higher levels of coagulopathy, as measured by a mean international normalized ratio (INR) of 1.46 on arrival in the trauma bay, compared with 1.19 for patients with high calcium levels. Massive transfusions were required in 29% of the patients with low levels of ionized calcium, compared with 12% of the group with high levels (P less than .0001).

A multivariable logistic regression analysis showed that low ionized calcium level was the only significant predictor of transfusion. Neither age, admission GCS, ISS, or coagulopathy significantly predicted transfusion requirements.

“Admission ionized calcium levels may facilitate rapid identification of patients requiring massive transfusion, allow us to have earlier preparation and administration of blood products, and may serve as a trigger to our blood bank to initiate our massive transfusion protocols,” Dr. O’Rourke said.

Dr. Matthew Rosengart, the invited discussant, noted that “for decades we have recognized that alterations in calcium, such as hypocalcemia, develop in our sickest of patients with prevalence upwards of 88% in the presence of severe sepsis. The elusive question is why.”

Further investigations should focus on determining how ionized calcium levels fit in with other scoring instruments that incorporate immediately available biochemical parameters, he said.

“How does this parameter, calcium, perform when other validated scores are incorporated into your model? Does it retain its association after more rigorous adjustment for case mix, including base deficit or lactate? Should ionized calcium complement or replace these instruments?” asked Dr. Rosengart, of the University of Pittsburgh Medical Center.

“I would say that any additional tool we can have to make something more predictive, so that our decision making is better, is useful,” Dr. O’Rourke replied.

The funding source for the study was not specified. The authors and Dr. Rosengart had no conflict of interest disclosures.