(Chest. 2005;127:246-250.)
© 2005
American College of Chest Physicians
Clinical Significance of Increased Lipase Levels on Admission to the ICU*
Janice Manjuck, MD, FCCP;
Joe Zein, MD;
Charles Carpati, MD and
Mark Astiz, MD, FCCP
* From Saint Vincent’s Catholic Medical Center of New York, New York Medical College, New York, NY.
Correspondence to: Mark Astiz, MD, FCCP, Saint Vincent’s Hospital, 153 W 11th St, New York, NY 10011; e-mail: mastiz{at}svcmcny.org
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Abstract
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Study objectives: To examine the incidence, risk factors, and sequelae associated with asymptomatic hyperlipasemia in the ICU.
Setting: Medical and surgical ICUs.
Patients: Two hundred forty-five adult critically ill patients admitted to an ICU for > 72 h with a diagnosis other than pancreatitis were studied prospectively.
Measurements: Serum amylase and lipase were measured on ICU admission and every third day until normalized. Clinical parameters including the incidence of ileus, the ability to tolerate enteral feeds, and the results of radiologic studies were also recorded.
Results: Hyperlipasemia was present in 40% of patients (peak, 1,183 ± 175 U/L; range, 209 to 8,620 U/L) [mean ± SEM]. Increased multiple-organ dysfunction scores, hypotension, anemia, mechanical ventilation (MV), bacteremia, elevated liver function test results, and elevated creatinine and triglyceride levels were all associated with increased lipase levels. In multivariate analysis, hypotension, anemia, elevated serum bilirubin, and MV were independently associated with higher lipase levels. Although mortality was not different, ICU length of stay and the duration of MV were significantly greater in patients with increased lipase levels (p < 0.05). Fifty patients underwent imaging studies. Pancreatitis was confirmed in 11 patients. The mean peak lipase value was significantly increased in patients with a positive study finding as compared to those with negative findings: 2,231 ± 715 U/L and 900 ± 234 U/L, respectively (p < 0.01). Enteral feedings, when initiated, were tolerated in 94% of patients with increased lipase levels and 97% of patients with normal lipase levels.
Conclusions: Elevated serum lipase levels are frequently encountered in critically ill patients. In the majority of these patients, enteral feedings are well tolerated and there are minimal clinical sequelae. Extremely high lipase levels may be associated with radiologic evidence of pancreatitis. Hypoperfusion and inflammatory processes associated with multiple-organ failure appear to be contribute to these increases.
Key Words: amylase • lipase • organ failure • pancreatitis
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Introduction
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Hyperamylasemia and hyperlipasemia are frequently encountered in critically ill patients. Pancreatic injury may result from splanchnic hypoperfusion following circulatory shock and major surgery.123 Medications, elevated triglyceride levels, and the development of biliary sludge may also predispose to pancreatitis.4 In addition, increases in serum amylase levels have been reported without clinical evidence of pancreatitis in patients with head injury, blunt trauma, and in patients following cardiac surgery.5678 In some cases, these elevations reflect nonpancreatic amylase production, while in other cases they are of pancreatic origin.5678 These increases in serum amylase and lipase, which are frequently clinically asymptomatic, raise important issues concerning the need for diagnostic imaging studies and the substitution of parenteral for enteral nutrition.
The objective of this study was to examine the incidence of hyperlipasemia in critically ill patients. Lipase levels were chosen because they normalize less rapidly than amylase levels, and have greater sensitivity and specificity for the diagnosis of pancreatitis.91011 Factors associated with hyperlipasemia and the course of patients with persistent hyperlipasemia were also examined.
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Materials and Methods
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Two hundred forty-five of 968 consecutive ICU admissions during the study period of January 1 to June 30, 1998, at St. Vincent’s Hospital were enrolled in the study. Of these patients, 89 patients were admitted to the medical ICU, 102 were admitted to the surgical ICU, and 54 were admitted to the neurosurgical ICU. These ICUs had total admissions of 276, 529, and 163 patients, respectively. Patients > 18 years of age were eligible for the study if they were admitted to the ICU for > 3 days. Patients were excluded if they were admitted with a diagnosis of pancreatitis, had a history of chronic renal insufficiency defined by a serum creatinine level > 2.0 mg/dL, if their ICU stay was < 3 days, or if their level of care was limited to comfort measures. The study protocol was approved by the institutional review board.
The data were collected prospectively. Serum amylase and lipase levels were measured in each eligible patient on ICU admission. Both enzymes were measured in patients with elevated ICU admission values every third day for the period of hyperlipasemia. The measurement was not repeated if the baseline value was normal unless clinically indicated. Clinical management was left to the discretion of the ICU team and the attending physician.
Demographic and clinical information was obtained for each patient. The acute physiology and chronic health evaluation (APACHE) II and the multiple-organ dysfunction score (MODS) were calculated.1213 Fever was defined as a temperature > 38.3°C, and hypotension was defined as a systolic BP < 90 mm Hg. The need for mechanical ventilation (MV) and a requirement for a positive end-expiratory pressure of > 5 cm H2O to maintain blood oxygen saturation >90% were also recorded. A triglyceride level > 300 mg/dL, transaminases or alkaline phosphatase levels more than twice the upper limit of normal, total bilirubin > 2 mg/dL, hemoglobin < 8 g/dL, plasma glucose level > 300 mg/dL, serum calcium level < 8 mg/dL or > 10 mg/dL, and a serum lactate level > 2.5 mEq/L were considered abnormal values. The presence of concurrent bacteremia, the performance of a radiologic study to diagnose pancreatitis, and the results of the study were recorded as well. The number of days of hyperlipasemia, tolerance of enteral feedings, presence of an ileus, and use of total parenteral nutrition were also recorded. Ileus was documented by clinical or radiographic evidence of abnormal intestinal motility; the decision to image the pancreas by either ultrasound or CT was left to the judgment of the primary team. The route of nutrition was also left to the primary team managing the patient.
The patients were classified into two groups. Group 1 included patients who had normal serum lipase values through the first 3 days of their ICU stay (range, 23 to 208 U/L). Group 2 patients had a serum lipase values above the upper limit of normal for our laboratory (> 209 U/L) within the first 3 days of ICU admission.
Data not normally distributed were log-transformed for analysis. However, for clarity of presentation, the results are expressed as untransformed values. Data are presented as mean ± SEM. Comparisons between groups were done using the one-way analysis of variance test for continuous variables, followed by the Tukey honestly significant difference test when appropriate. Categorical variables were compared using the Pearson 
2 test; p < 0.05 was considered statistically significant. Statistical analysis was performed using JMP statistical software (Version 4.0; SAS Institute; Cary, NC).
Odds ratios and 95% confidence intervals were estimated on the basis of multivariate logistic-regression analysis, which was used to evaluate the model, in which the dependent variable was lipase. The initial model included the following independent variables: age; abnormal temperature; hypotension; APACHE II score; increased alkaline phosphatase, bilirubin, transaminases, triglycerides, or creatinine levels; low hemoglobin; and the need for MV. Continuous variables were introduced as uncorrected data. A model showing significant main effect for the predictors was formulated.
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Results
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There was no difference in the age of the patients, the presence of underlying HIV disease, or history of alcohol use between group 1 and group 2 (Table 1
). APACHE II scores and MSOF results were significantly higher in group 2 patients. The distribution of patients between the different ICUs was not different. Hyperlipasemia was present in 99 patients (40%). In Group 1, 24 of 145 patients (17%) had elevated amylase levels, whereas 57% of the patients in group 2 had elevated amylase levels. The peak lipase value was 82 ± 5 U/L in group 1 and 1,183 ± 175 U/L in group 2. There was a significant correlation between peak lipase and peak amylase values (r2 = 0.32, p < 0.001) and between the peak lipase value and number of days of persistent hyperlipasemia (r2 = 0.36, p < 0.001). Hyperlipasemia persisted for 8.3 ± 0.9 days in group 2 patients.
The underlying diagnoses are listed in Table 2
. Lipase levels were highest in patients requiring emergency surgical procedures (Table 2). Group 2 patients had a greater incidence of hypotension, fever, and MV than group 1 patients (Table 3
). The plasma triglycerides, bilirubin, transaminases, alkaline phosphatase, and creatinine levels were elevated in a greater percentage of group 2 patients (Table 3). The ICU length of stay and the duration of MV were longer in group 2 patients (Table 4
). There was a greater incidence of ileus in group 2 patients, which approached significance; however, there was no difference in the ability to tolerate enteral feeding between the two groups. ICU mortality was 13% in group 1 patients and 18% in group 2 patients (not significant). In the multivariate analysis, hypotension, fever, low hemoglobin, elevated bilirubin level, and the need for MV were associated with the presence of increased lipase levels (Table 5
). The incidence of these four variables was similar in group 2 patients with higher and lower levels of lipase elevation.
Ultrasound (2 patients) or CT (9 patients) confirmed pancreatitis in 11 of 50 group 2 patients (22.0%). None of the patients had biliary pancreatitis. The peak lipase value in patients who had a negative radiologic study was 900 ± 234 U/L, compared to 2,231 ± 715 U/L (p < 0.01) in those who had a positive study result. Patients with a positive imaging study finding had increased mortality; however, no other significant differences in associated organ dysfunction or severity scores were observed (Table 6
). Accordingly, when group 2 patients with increased lipase and negative imaging study results were compared with group 1 patients, the same clinical differences that were present between group 1 and the combined group 2 patients remained.
An ileus was present in 23 of 245 patients (11%). Peak lipase levels were 1,162 ± 356 U/L in patients with an ileus and 448 ± 75 U/L (p < 0.05) in patients without an ileus. An imaging study was requested in 16 of the patients with an ileus, and 4 patients demonstrated radiologic evidence of pancreatitis. These patients had extremely high lipase levels (4,035 ± 158 U/L). In contrast, patients with ileus and a negative radiologic study finding had a mean lipase value of 550 ± 190 U/L. Intragastric or intraduodenal feeds were tolerated in six patients who had positive imaging study results, they were not attempted in four patients, and only one patient with a positive radiologic study finding for pancreatitis did not tolerate enteral feeds.
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Discussion
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Elevations in serum amylase are frequently observed in patients admitted to an ICU without a primary diagnosis of pancreatitis. The incidence of hyperamylasemia ranges from 30 to 80% in groups of patients with traumatic injury, head injury, and following cardiac surgery.5678 In many of these previous reports, the elevations in serum amylase have been found to be of nonpancreatic origin; however, when coupled with increases in serum lipase, the hyperamylasemia was usually of pancreatic origin.6 This study examined serum lipase, which is considered more specific than serum amylase for the diagnosis of pancreatitis.91011 The 40% incidence of increased serum lipase is similar to the previously observed increases in serum amylase. Although there were no significant differences in the incidence of increased serum lipase levels between medical and surgical patients, the highest values were observed in patients requiring emergency surgery.
Ischemic injury to the pancreas is one factor that is postulated to contribute to increases in serum lipase and amylase in critically ill patients. A direct correlation between increases in serum pancreatic amylase levels and aortic cross-clamping time has been reported in patients undergoing surgery for thoracoabdominal aneurysms.2 In a small prospective series1 of 13 patients with circulatory shock, each of the patients had increases in serum amylase and lipase in their subsequent course. Hypotension in the setting of traumatic injury has also been associated with the development of hyperamylasemia in some, but not all, studies.514 Similarly microscopic evidence of pancreatic autodigestion has been described in animal models of hemorrhagic and septic shock, and in postmortem studies of patients with septic shock.15 In our study, the increased lipase levels were associated with hypotension, and the highest lipase levels occurred in patients undergoing emergency surgery. Both of these observations are consistent with a role for ischemia in mediating these elevations.
Patients with hyperlipasemia were also characterized by significantly higher APACHE II and MSOF results. The association between increased lipase levels and hypotension, the need for MV, anemia, and increases in serum bilirubin suggests that these elevations represent a pancreatic manifestation of multisystem organ failure. Nitric oxide, oxygen radicals, platelet activating factor, endotoxin, and peroxynitrite have all been reported to contribute to pancreatic injury in different models of hemorrhagic and septic shock.16171819 Indeed, impairment of pancreatic exocrine function has been described in patients with septic shock in the absence of significant serum pancreatic enzyme elevation or histologic evidence of pancreatic damage.20 This report indicates that a broad spectrum of pancreatic dysfunction may be evident in patient with septic shock.
The majority of the patients with elevated lipase levels were intubated and sedated, making the clinical diagnosis of pancreatitis problematic. There was a modest increase in the incidence of patients acquiring an ileus with increased lipase levels, but there was no significant difference in the ability to tolerate enteral feeds between patients with and without increased lipase levels. Indeed, the majority of patients (69%) with increased lipase levels tolerated enteral feeds. Imaging studies were obtained in 50% of the patients with elevated lipase levels. Radiographic evidence of pancreatitis was present in a minority of these patients and was associated with greater elevations of lipase levels. Although mortality was increased in patients with positive imaging study findings, no other differences in severity scores or comorbidities were noted in comparison to patients with negative imaging study findings. Other than ileus and the inability to tolerate enteral feeds in some of the patients with positive imaging study findings, there were no other manifestations of severe clinical pancreatitis. These observations are consistent with previous reports167 that have noted that in patients who have increases in pancreatic enzymes in the presence of a critical illness other than pancreatitis, the elevations usually are not associated with clinical symptoms or complications.
In conclusion, elevations of serum lipase are frequently encountered in critically ill patients. Despite these elevations, enteral feedings are usually well tolerated and there are minimal clinical sequelae. Extremely high enzyme levels may be associated with radiologic evidence of pancreatitis. Hypoperfusion and inflammatory processes associated with multiple-organ failure appear to contribute with these increases.
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Footnotes
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Abbreviations: APACHE = acute physiology and chronic health evaluation; MODS = multiple-organ dysfunction score; MV = mechanical ventilation
Received for publication January 12, 2004.
Accepted for publication May 28, 2004.
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References
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Abstract
Introduction
