Journal of Pediatric Surgery (2011) 46, 923–926
www.elsevier.com/locate/jpedsurg
Utility of amylase and lipase as predictors of grade of injury or outcomes in pediatric patients with pancreatic trauma Richard Herman a , Ken E. Guire b , Randall S. Burd c , David P. Mooney d , Peter F. Ehlrich a,⁎ a
University of Michigan School of Medicine, Ann Arbor, MI 48109, USA Biostatistics Department, University of Michigan, Ann Arbor, MI 48109, USA c Childrens National Medical Center, Washington, DC 20010, USA d Boston Children's Hospital, Boston, MA 02115, USA b
Received 4 February 2011; accepted 11 February 2011
Key words: Pediatric trauma; Pancreatic injury; Amylase; Lipase
Abstract Introduction: Grade of injury, serum amylase, and lipase are markers used to assess pancreatic injury. It is unclear how amylase and lipase relate to grade of injury or predict outcome. We hypothesize that serum amylase and lipase are good predictors of grade of injury and outcomes in patients with pancreatic trauma. Methods: This study is a multicenter review from 9 pediatric trauma centers of all children admitted to their institution over 5 years with a pancreatic injury. Initial as well as peak amylase and lipase values were analyzed with relation to pancreatic grade, length of stay, and outcomes. Results: One hundred thirty-one records were analyzed. There were 44 girls and 85 boys with an average age of 9.0 ± 0.4 years. The mean injury severity score (ISS) score was 15.5 ± 1.2 SE. The average length of stay (in days) was analyzed by grades 0 (3.93), 1 (7.73), 2 (13.4), 3 (18.4), 4 (31), and 5 (13.5). Neither initial nor peak amylase/lipase correlated with grade of injury. Neither amylase nor lipase predicted length of stay or mortality. Maximal amylase was highly predictive of developing a pseudocyst. Conclusion: There seems to be limited value for repetitive routine amylase and lipase levels in the management of pediatric trauma patients with pancreatic injury. © 2011 Elsevier Inc. All rights reserved.
Trauma is a disease process with identifiable and reproducible patterns. Unfortunately, class 1 data and prospectively designed clinical trials (observational or interventional) are limited for pediatric trauma care, and ⁎ Corresponding author. Section of Pediatric Surgery, University of Michigan Hospitals, F7822 Mott Children's Hospital SPC 5231, 1500 E Medical Center, Ann Arbor, MI 48109, USA. Tel.: +1 734 613 3303; fax: +1 734 647 8111. E-mail address:
[email protected] (P.F. Ehlrich). 0022-3468/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2011.02.033
our practices are driven by empirically derived approaches (retrospective data and observational data). The Institute of Medicine and other national authorities have identified not only critical deficiencies in pediatric trauma care but also insufficient research to address these deficiencies [1]. One problem is that several pediatric injuries are rare, and an individual center may only see a few cases of a distinct injury. In these clinical situations, published series often contain too few cases to make meaningful conclusions or identify priorities for study. One method to overcome this
924
R. Herman et al.
limitation is to obtain a larger series of data from multiple pediatric trauma centers [2]. Collaborating pediatric trauma centers could identify research priorities and develop hypotheses, first through retrospective studies, then testing these hypotheses through prospective multicenter trials. Pancreatic injury in children is one such example. The incidence of children sustaining a pancreatic injury is low [3,4]. Furthermore, management of pancreatic injuries remains a challenge. Areas of uncertainty exist with respect to diagnosis, relevant prognostic factors, and treatment. Thus, there has been an ongoing debate about the optimal approach to treating pancreatic injuries. Blood amylase and lipase are frequent, and repetitive laboratory tests have been used to identify and manage traumatic pancreatic injury [5-9]. The utility and cost-effectiveness of serum amylase and lipase as a screening tool for pediatric pancreatic trauma have been questioned by Adamson et al [5], who suggest that these tests have a low sensitivity and specificity. Alternatively, Matusno et al [7] and Tsunemasa et al [10] examined the effectiveness of delayed amylase and lipase levels and suggested that they may be of some utility in identifying a pancreatic injury. A research gap exists as to whether amylase and lipase relate to grade of injury, or whether they can be used to direct therapy or predict outcome. We hypothesize that serum amylase and lipase are good predictors of the grade of injury and of the outcomes in patients with pancreatic trauma. The purpose of this study was to test this hypothesis through a multicenter review of pediatric pancreatic injuries.
1. Methods This was a multicenter retrospective review from 9 pediatric trauma centers (see participating centers in acknowledgements). All contributing centers are members of the American Pediatric Surgery Association Trauma Committee. Institutional review board approval was obtained at each
Table 2 injury
Total number of patients per grade of pancreatic
Grade
0
I
II
III
IV
V
Total no. of patients Length of stay (d)
15 3.3
48 7.7
28 13.4
25 18.4
10 31
3 13.5
center. Each institution collected data on children (b18 years old) with a documented pancreatic injury. A common data collection form was used, and 5 years of data was collected (2003-2008). The data were then sent to a central institution (DC Children's Hospital) for collating and entry into the database. Demographics, mechanism of injury, standard injury data, radiographic evaluations, treatment, complications, and length of stay were all collected. The grade of pancreatic injury was determined by radiology (computed tomography (CT) scan or ultrasound) and/or operative findings. Pancreatic injuries were graded using all available data including radiographic imaging and operative reports according to the American Association for the Surgery of Trauma guidelines (Table 1) [11]. Initial and peak amylase and lipase values were analyzed in relation to pancreatic injury grade, length of stay, and outcomes. Standard laboratory ranges at our institution defined normal amylase and lipase values as being 30 to 100 international units/L (U/L) for amylase and 5 to 50 U/L for lipase. The CT scans were performed as part of the trauma evaluation and were not specifically looking for a pancreatic injury. The indications were institution specific and based on the mechanism of injury and clinical examination. A secondary outcome assessed the length of stay in relation to grade of pancreatic injury. Statistical analysis was performed using χ2 and Pearson correlation coefficient. A P value of less than .05 and a correlation coefficient (r2) greater than 0.95 were considered significant [12-15].
2. Results Table 1 American Association for the Surgery of Trauma pancreatic injury grades Pancreatic injury scale Grade Type of injury I II
III IV V
Description
Hematoma Minor contusion without duct injury Laceration Superficial, no duct injury Hematoma Major contusion, no duct injury or tissue loss Laceration Major laceration, no duct injury or tissue loss Laceration Distal transaction or parenchymal injury with duct injury Laceration Proximal transection involving ampulla Laceration Massive disruption of pancreatic head
The study took place between 2003 and 2008. One hundred thirty-one cases were submitted. There were 85 boys, 44 girls, and 2 cases where the gender was not recorded. The average age was 9.0 ± 0.4 years (mean ± SD). The mean ± SD ISS score was 15.5 ± 1.2. There were 12 deaths. Motor vehicle collisions and bicycle crashes were the most common injury mechanisms. For this study, 111 cases had complete data for amylase, Table 3
Initial and maximal amylase and lipase by grade
Grade
0
I
II
III
IV
V
Initial amylase Initial lipase Maximal amylase Maximal lipase
306 959 350 947
406 1180 609 2069
576 1575 936 7027
364 1360 597 2540
524 1462 1079 1898
155 1023 735 4019
Amylase and lipase in patients with pancreatic trauma
925
Table 4 Relationship of amylase and lipase to length of stay and grade of injury
the grade of injury, complications, and outcomes in patients with pancreatic trauma. Early determination of the grade of the injury can help treatment options and increase awareness for potential complications. Serum amylase and lipase are regularly obtained when evaluating pancreatic disease. Our hypothesis was that serum amylase and lipase are good predictors of the grade of injury or of outcomes in patients with pancreatic trauma. The results of this study do not support this hypothesis. Neither initial nor maximal amylase/ lipase has any predictive utility for grade of injury, or length of stay, or outcomes in a child with pancreatic trauma. However, a maximal amylase level greater than 1100 U/L was predictive for developing a pseudocyst. The results of this study are consistent with other smaller series in the literature [5,10,23]. In 1975, a case series of 5 patients suggested that there was no correlation between amylase levels and degree of injury [23]. In 2 related studies, the utility and cost-effectiveness of serum amylase and lipase as screening tools for pediatric pancreatic trauma have shown poor sensitivity and specificity [5,10]. Alternatively, the results of this study seem to be in contradiction to other single-center series. Matusno and colleagues [7] suggested that a delayed (N2 hours) serum amylase and lipase level was predictive of pancreatic injury and correlated with the severity of the injury. Nadler et al reported that high (peak) amylase (N200 U/L) and lipase levels (N1800 U/L) were more consistent with major duct disruptions [8]. We found that the maximal amylase predicted the likelihood of developing a pseudocyst but not the diagnosis, grade of injury, severity of injury, or possibility of a ductal disruption. One possible explanation for our different findings may be the larger and more diverse numbers of children in this multicenter study. The centers represented in this collaboration comprise urban, suburban, and rural pediatric trauma centers. The data from this, as well as previous studies, allows us to question some of the routine practices for our trauma patients [24-26]. If serum amylase and lipase are not a good screening test and do not predict injury severity length of stay or outcomes, what value do they provide for patient care? Adamson et al [5] (based on 2003 financial data) suggested that the routine use of amylase and lipase added $24,862 in hospital charges per patient. If amylase and lipase have such limited utility, why obtain them at all? This suggestion is not novel. Fenton and colleagues [24] showed that limiting standard pediatric trauma laboratory investigations increased the uniformity of care and reduced costs without compromising quality. Our current approach also uses minimal blood work during the initial and subsequent phases of trauma care. Amylase and lipase are not part of our standard laboratories. The diagnosis of a traumatic pancreatic injury is best made through radiologic evaluation, specifically with a CT scan of the abdomen, which has a high sensitivity and specificity. It seems more logical to wait until a pancreatic injury is detected and then monitor the serum amylase level until it peaks. Alternatively, if the
Amylase Initial Maximum Lipase Initial Maximum
Length of stay (r2)
Injury grade (P values)
0.089 0.254
.678 .176
0.011 0.004
.969 .512
and 91 had complete data for the lipase evaluation. The total number of patients and the average length of stay (in days) by grade are shown in Table 2. The average initial and maximal amylase and lipase values by grade are shown in Table 3. Neither initial nor peak amylase/lipase levels were significant predictors of a specific grade of injury, nor did either correlate with length of stay (Table 4). The presence of multiple injuries impacted these results. However, maximal amylase (N1100 U/L) was highly predictive of developing a pseudocyst or another complication (P b .003). Finally, maximal amylase or lipase levels were not predictive of mortality (P = .29 and .31).
3. Discussion In December 2008, the World Health Organization released the “World Report on Child Injury Prevention” that established injury as the number 1 pediatric public health problem in the world [16]. Despite this report, national authorities have identified not only critical deficiencies in pediatric trauma care but also insufficient research to address these deficiencies. One factor that contributes to this problem is the limited number seriously injured children treated at a single center [17]. Thus, multicenter collaboration is needed to develop and understand how best to treat, prevent, and rehabilitate seriously injured children [18]. This study begins to address the problem of traumatic pancreatic injury in children through a multicenter review from 9 major pediatric trauma centers who are part of the American Pediatric Surgical Association (APSA) trauma committee. Pancreatic injury comprises between 2% and 9% of injured children admitted to trauma centers [3,4]. Most cases of pancreatic injury are minor grade 0 or 1, with few major pancreatic duct disruptions [3,19]. Despite continued efforts at creating a standard protocol, the optimal management of pediatric patients with pancreatic injury remains poorly defined, at least in part because of the small number of patients available for analysis [19-22]. To date, only 1 study used multiple pediatric trauma center data to assess pancreatic injury. That study focused on factors that could predict the failure of nonoperative management. This study's goal was to evaluate factors that may help with patient management, specifically predictors regarding
926 clinical scenario does not support pancreatic injury or an abdominal injury, and the amylase/lipase is normal, one could argue that the patient does not need a CT and its consequent risks of radiation exposure. Those with levels above 1100 U/L should be followed by ultrasound looking for pseudocyst development. The limitations of this study are inherent in its retrospective design. In addition, although the data set contained 129 evaluable cases, only 111 for amylase and 91 for lipase had complete information for evaluation. Although we were able to show that the amylase and lipase had no utility for predicting injury severity, length of stay, or outcomes, a high amylase level predicted an increased risk of developing a pseudocyst. However, we were not able to evaluate whether decreasing levels correlated with resolution or the persistence of symptoms. Finally, we were not able to confirm the timing of the initial laboratory tests. In the series by Matusno et al [7], it was suggested that an elevated amylase at 2 hours is useful in predicting pancreatic injury. Although the correlation with grade or length of stay does not exist, the data seem to suggest that any initial elevation in either of these markers suggests pancreatic injury of some sort and that imaging is likely required to ascertain its severity. This does support the finding in the study of Matusno et al. However, because most trauma patients with a mechanism suggesting an abdominal injury will have an abdominal CT scan, the diagnosis of a pancreatic injury has probably already been determined [6,7,27,28]. Taken together, this multicenter retrospective study presents evidence suggesting that repetitive and routine amylase and lipase measurements are of limited value in the management of pediatric trauma patient with pancreatic injury.
Acknowledgments The authors thank the members of the American Pediatric Surgical Association Committee on Trauma Participating Institutions and Surgical Leads: David P. Mooney, MD (Boston Children's Hospital, Boston, MA); Randall Burd, MD (Childrens National Medical Center, Washington, DC); Robert Letton, MD (Oklahoma Children's Hospital, Oklahoma City, OK); Katheryn Bass, MD (Cook Children's Hospital, Chicago, IL); Mindy Statter, MD (Comer Children's Hospital at the University of Chicago, Chicago, IL); Richard Falcone, MD (Cincinnati Childrens Hospital, Cincinnati, OH); Peter Ehrlich, MD (CS Mott Children's Hospital, Ann Arbor, MI); Jon Groner, MD (Nationwide Children's Hospital, Columbus, OH); David Foley, MD (Kosair's Children's Hospital, Louisville, KY).
References [1] Institute of Medicine. Emergency medical services for children. Washington (DC): Institute of Medicine; 1993.
R. Herman et al. [2] Mooney DP, Rothstein DH, Forbes PW. Variation in the management of pediatric splenic injuries in the United States. J Trauma 2006;61: 330-3. [3] Jacombs ASW, Wines M, Holland AJA, et al. Pancreatic trauma in children. J Pediatr Surg 2004;39:96-9. [4] Mattix KD, Tatraria M, Holmes J, et al. Pediatric pancreatic trauma: predictors of nonoperative management failure and associated outcomes. J Pediatr Surg 2007;42:340-4. [5] Adamson WT, Hebra A, Thomas PB, et al. Serum amylase and lipase alone are not cost-effective screening methods for pediatric pancreatic trauma. J Pediatr Surg 2003;38:354-7. [6] Bradley EL, Young PR, Chang M, et al. Diagnosis and initial management of blunt pancreatic trauma: guidelines from a multiinstitutional review. Ann Surg 1998;227:861-9. [7] Matusno WC, Huang CJ, Garcia NM. Amylase and lipase measurements in paediatric patients with traumatic pancreatic injuries. Injury Int J Care Injured 2009;40:66-71. [8] Nadler EP, Gardner M, Schall LC, et al. Management of blunt pancreatic injury in children. J Trauma 1999;47:1098-103. [9] Wood JH, Patrick DA, Bruny JL, et al. Operative vs nonoperative management of blunt pancreatic trauma in children. J Pediatr Surg 2010;45:401-6. [10] Tsunemasa T, Sugimoto K, Hirata M, et al. Serum amylase level on admission in the diagnosis of blunt injury to the pancreas: its significance and limitation. Ann Surg 1997;226:70-6. [11] Moore EE, Coghill TH, Malangoni MA, et al. Organ injury scaling. Surg Clin North Am 1995;75:293-303. [12] SPSS Inc. SPSS Base 10.0 for Windows User's Guide. Chicago (Ill): Prentice Hall Professional; 1999. [13] Kaplan EL, Meier P. Non-parametric estimation from incomplete observations. J Am Stat Assoc 1958;33:457-81. [14] Peto R, Peto J. Asymptotically efficient rank invariant test procedures. J R Stat Soc (A) 1972;135:185-206. [15] Fischer RA. On the interpretation of chi squared from contingency tables, and the calculation of P. J R Stat Soc 1922;855:87-94. [16] Peden M, Oyegbite K, Ozanne-Smith J, et al. World report on child injury prevention. Peden M. 1-232. Geneva Switzerland: World Helath Organization; 2008. [17] National Center for Injury Prevention and Control. CDC injury research agenda; 2002. [18] Jaffe DM. Research in emergency medical services for children. Pediatrics 1995;96:191-4. [19] Canty TG, Weinman D. Management of major pancreatic duct injuries in children. J Trauma 2001;50:1001-7. [20] Meier DE, Coln D, Hicks BA, et al. Early operation in children with pancreatic transaction. J Pediatr Surg 2001;36:341-4. [21] Shilyansky J, Sena L, Dreller M, et al. Non-operative management of pancreatic injuries in children. J Pediatr Surg 1998;33:343-9. [22] Loungnarth R, Blanchard H, Saint-Vil D, et al. Blunt pancreatic injuries in children. Ann Chir 2001;126:992-5. [23] Moretz JA, Campbell DP, Parker DE, Williams GR. Significance of serum amylase level in evaluating pancreatic trauma. Am J Surg 1975; 130:739-41. [24] Fenton SJ, Peterson DN, Connors RC, et al. A standard pediatric trauma laboratory panel: a plea for a minimalist approach. J Trauma 2009;66:703-6. [25] Capraro A, Mooney DP, Waltzman ML. The use of routine laboratory studies as screening tools in pediatric abdominal trauma. Pediatr Emerg Care 2006;22:480-4. [26] Keller MS, Coln CE, Trimble JA, et al. The utility of routine trauma laboratories in pediatric trauma resuscitations. Am J Surg 2004;188: 671-8. [27] Ilahi O, Bochicchio GV, Scalea TM. Efficacy of computed tomography in the diagnosis of pancreatic injury in the adult blunt trauma patients: a single institutional study. Am Surg 2002;68:704-7. [28] Jobst MA, Canty TG, Lynch FP. Management of pancreatic injury in pediatric blunt abdominal trauma. J Pediatr Surg 1999;34:818-24.