Journal of Pediatric Surgery 49 (2014) 1719–1722
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Characterization of acute appendicitis in diabetic children Camille L. Stewart a,b,⁎, Colleen L. Wood a,c, John F. Bealer a,b a b c
Department of Surgery, University of Colorado School of Medicine, Aurora CO, United States Division of Pediatric Surgery, Children's Hospital Colorado, Aurora, CO, United States Division of Pediatric Endocrinology, Children's Hospital Colorado, Aurora, CO, United States
a r t i c l e
i n f o
Article history: Received 18 August 2014 Accepted 5 September 2014 Key words: Diabetes Appendicitis
a b s t r a c t Purpose: Children with diabetes mellitus (DM) who develop acute appendicitis can present a diagnostic and clinical challenge. No studies have examined this population since the advent of multiple dose insulin therapy, computed tomography, and laparoscopic surgery. We sought to characterize these children to identify their differences and how to best care for them. Methods: We retrospectively examined the medical records of children with a preexisting diagnosis of DM treated for acute appendicitis. Values are presented as the mean ± the standard error of the mean, and Student's t-test was used for statistical comparison. Results: We identified 18 diabetic children treated for acute appendicitis, making this the largest series of its kind. These children had similar presentations compared to non-diabetics, with the exception of often presenting without fever (83.3% with an initial temperature b 38 C). All children developed significant postoperative hyperglycemia (average high 382 ± 18 mg/dL), and most had glycemic control for ≤50% of the hospitalization (14/18, 77.8%), but they otherwise had typical postoperative courses. Conclusions: Diabetic children with appendicitis are often afebrile at presentation and have serum glucose levels that are difficult to control. Collaboration with pediatric endocrinologists is needed to appropriately manage these children during their hospitalization. © 2014 Elsevier Inc. All rights reserved.
Conventional clinical wisdom has historically held that differing disease processes occurring simultaneously are rare in children. Contemporary realities are changing given that children are becoming more adult-like in their development of chronic diseases such as obesity [1,2], hypertension [3], and diabetes mellitus (DM) [4,5]. Surprisingly, there is a paucity of literature regarding children with acute surgical illnesses and concomitant chronic disease. Appendicitis is a common surgical disease that frequently affects children and adolescents [6]. A typical constellation of signs, symptoms, laboratory, and radiologic tests are used to diagnose and determine management of these often otherwise healthy patients [7,8]. The diagnosis of appendicitis becomes more difficult in children with other medical problems, including DM. While it is known that adult diabetics with appendicitis have inferior outcomes [9], little is known about their pediatric counterparts. Given recent increased interest in glucose control and its relationship to morbidity and mortality in critically ill and surgical patients, we believe that it is important to improve our understanding of diabetic children who develop appendicitis.
preexisting diagnosis of DM that were subsequently treated for acute appendicitis from 2003 to 2013. All children in this cohort received diabetic care within a specialized diabetic program managed by pediatric endocrinologists. Information collected included basic demographics and clinical information regarding diabetic control, presentation, diagnosis, and postoperative care. Leukocytosis was defined as a white blood count (WBC) N10 × 10 3/μL. Diabetes compliance was defined based on the most recent hemoglobin A1c prior to the development of appendicitis, with a goal value b 8% for children 6–12 years old, and b7.5% for children 13–19 years old [10]. Glucose was considered controlled during hospitalization for values ≤ 180 mg/dL. Glycemic control is reported as the percentage of glucose checks ≤ 180 mg/dL compared to the total number of glucose checks during the hospitalization. Alvarado's score was calculated according to his original manuscript [8]. Study variables were available for all children except where noted otherwise. Continuous variables are presented as the mean ± the standard error of the mean, and Student's t-test was used to compare continuous variables.
1. Methods 2. Results After obtaining approval from our institutional review board, we retrospectively examined the medical records of children with a
2.1. Demographics
⁎ Corresponding author at: Department of Surgery, University of Colorado School of Medicine, 12631 E. 17th Ave., C302, Aurora, CO 80045, United States. Tel.: +1 720 777 4612; fax: +1 303 724 2682. E-mail address: [email protected] (C.L. Stewart).
We identified 18 children with DM who were treated for acute appendicitis. Demographic information is reported in Table 1. The average age at diagnosis of appendicitis was 11.9 ± 0.8 years (range
http://dx.doi.org/10.1016/j.jpedsurg.2014.09.003 0022-3468/© 2014 Elsevier Inc. All rights reserved.
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C.L. Stewart et al. / Journal of Pediatric Surgery 49 (2014) 1719–1722
Table 1 Demographics and presenting signs/symptoms of diabetic children with appendicitis. Qualifier Demographics Age (yrs) Duration of DM (yrs) Male Hx of noncompliance Hx of DKA Presenting symptoms/signs Abdominal pain Nausea/vomiting Diarrhea Fever N38 °C Tachycardia N100 BPM Leukocytosis N10 × 103/μL
Avg or N (STE or %) 11.9 (0.8) 3.7 (0.8) 11 (61.1%) 14 (77.8%) 3 (16.7%) 18 (100%) 16 (88.9%) 55 (27.8%) 3 (16.7%) 12 (66.7%) 15 (88.2%) Fig. 1. Diabetic children with appendicitis grouped by Alvarado's number.
7.2–19.0 years) and the average duration of diabetes was 3.7 ± 0.8 years (range 26 days–12.7 years). There were 11 males and 7 females, and all but one child had type 1 DM. Five children (27.7%) managed their blood glucose with an insulin pump. The other type I diabetics were treated with multiple daily injection therapy using both short and long acting insulins, and the only type II diabetic was treated with Metformin alone. The majority of children (77.8%) had a history of noncompliance based on their most recent hemoglobin A1c values, and 16.7% had a history of diabetic ketoacidosis (DKA). None of the children had a history of chronic abdominal pain, and 1 child had previous abdominal surgery.
and 17/18 (94.4%) appendectomies were performed laparoscopically. Perforation was found in 6/18 (33.3%) children. One child had a normal appendix with an appendicolith. Intra-operatively, most of the children (11/17, 64.7%) received no special or specific management of their serum glucose other than monitoring. Only one child received a bolus of insulin intra-operatively. All children with insulin pumps maintained basal insulin infusion during surgery except one whose pump insertion site was in the operative field.
2.2. Presentation
Pediatric endocrinology aided in glucose management for the majority of our patients (13/18, 72.2%). Children who managed their diabetes with a pump continued to do so postoperatively, and generally managed their insulin administration independently. Most stayed on their home basal insulin rate, with adjustments of 10-20% above or below basal rate for hyper or hypoglycemia, respectively. The rest of the children were managed with insulin for blood sugar correction and carbohydrate coverage postoperatively. This was often similar to their home regimen, with long-acting insulin in the morning and/or evening, and a fast acting insulin administered with meals to correct hyperglycemia and to cover carbohydrate consumption. When the endocrinology service was involved, they often adjusted these regimens according to prior blood glucose measurements. Every child in this study experienced hyperglycemia postoperatively, with an average peak serum level of 382 ± 18 mg/dL (range 262–551 mg/dL). Most children (14/18, 77.8%) had glucose levels controlled ≤50% of their hospitalization. Glucose control was similar for children with and without perforation (37% ± 4% versus 36% ± 8%, p = 0.98), and for those with and without an insulin pump (45 ± 10% versus 34 ± 6%, p = 0.34). Children whose management was aided by the pediatric endocrinology team had lower peak glucose values (375 ± 18 versus 402 ± 50 mg/ dL), but this difference was not statistically different (p = 0.54). Most children (15/18, 83.3%) had their diet advanced to a diabetic regular diet within one day of surgery. Glucose checks and short acting insulin administration were then generally adjusted to only before meals and at bedtime. The average length of stay was 3.2 ± 0.7 days, which was significantly longer for children with perforated (5.9 ± 1.4 days) compared to nonperforated appendicitis (1.8 ± 0.3 days, p = 0.001). No child developed DKA during their hospitalization, suffered from wound complications, or developed a postoperative abscess, and no child was readmitted with the exception of one child who received an interval laparoscopic appendectomy after initial drainage of an abscess.
Presenting signs and symptoms are presented in Table 1. The history of present illness included abdominal pain (100%), nausea/vomiting (88.9%), diarrhea (27.8%), and dysuria (5.6%). Ten children (55.6%) described the classic migration of pain to the RLQ, and 8 (44.4%) had rebound tenderness on exam. Children presented on average 3.6 ± 1.6 days after the onset of symptoms. Deviations in typical diabetic management or issues with glucose control after the onset of symptoms were only reported in 6/18 (33.3%). Only 3/18 (16.7%) children were febrile with a temperature N38 °C at presentation (average temperature 37.2 ± 0.2). Tachycardia (average heart rate 110.6 ± 6.5) was a commonly noted physical finding, seen in 12/18 (66.7%) of patients. WBC was measured in 17/18 children, and leukocytosis (average WBC count 15.1 ± 0.9) was found in the majority (15/17, 88.2%). The average presenting serum glucose was 188 ± 16 (range 85–306). Of the 10 children who had a urinalysis performed on presentation, 7/10 had excess glucose detected, and 7/10 had ketones detected. No child was acidotic on presentation, although objective evidence of acid/base status was not uniformly measured. The average bicarbonate was 21 ± 1 (n = 10, range 18–25), the average pH was 7.43 ± 0.02 (n = 5, range 7.39-7.49) and the average base deficit was 0.3 ± 0.6 (n = 5, range − 2 to 1.4). We were able to calculate Alvarado's score [8] for 15 children; all but 1 had a score ≥5 (Fig. 1). 2.3. Diagnosis and treatment All patients had imaging studies, either a CT scan (14/18, 77.8%) or ultrasound (4/18, 22.2%) of the abdomen, to assist in making the diagnosis of appendicitis. While nil per os (NPO), children without a pump continued to received their long acting insulin such as glargine (trade name: Lantus) for glucose control. Those with a pump continued to receive insulin at the basal setting. Metformin was held for the type II diabetic patient because of the risk of lactic acidosis. Blood glucose was checked every 2–4 hours, and treated with short acting insulin such as lispro (trade name: Humalog). The majority of children were treated with appendectomy within 24 hours of presentation (16/18, 88.9%),
2.4. Postoperative management
3. Discussion This study began by asking if diabetic children with acute appendicitis differed from nondiabetic children in their presentation, treatment,
C.L. Stewart et al. / Journal of Pediatric Surgery 49 (2014) 1719–1722
or outcomes. A literature search revealed a single previous study from 1988 characterizing diabetic children with appendicitis [11]. The relevance of this work to today's patients is limited since treatment has changed dramatically in the interim; multiple daily injections of insulin [12], continuous insulin infusion pumps [13], the widespread use of imaging for the diagnosis of appendicitis [14], and laparoscopic appendectomy [15] all are currently routine and have dramatically impacted the care of these patients. In this study we collected the largest cohort of diabetic children with appendicitis ever reported to update their clinical characteristics and facilitate their surgical care. Appendicitis is the most common surgical disease of the abdomen, and most commonly affects children during the second decade of life [6]. Diagnosis remains a significant clinical challenge demanding full consideration of a patient''s clinical signs, symptoms, laboratory findings, and imaging [7]. Abdominal pain is a nearly universal symptom of appendicitis but unfortunately, appendicitis is not a universal cause of childhood abdominal pain [7]. Many other common illnesses produce abdominal pain, and this is particularly true in children with other medical issues such as DM. Children with DM often suffer from abdominal pain [16], which can be caused by impaired gastric emptying related to hyperglycemia or neuropathy [17,18]. Abdominal pain is also a common symptom in DKA [19]. DKA is more common in diabetic adolescents, who frequently have poor glycemic control related to psychosocial and compliance issues [20,21]. This suggests that appendicitis in children with DM could pose a particular diagnostic challenge. Overall, children typically have some delay in surgical care and a higher rate of appendix perforation compared to adults [22,23]. While we do not have a direct control group for comparison, we were surprised to find that the duration of symptoms and perforation rate of our diabetic appendicitis patients were within the reported ranges for nondiabetic children with appendicitis [22,23]. It is possible that these children had improved or facilitated access to medical care from managing their DM prior to developing appendicitis. All the children in our series were part of an intensive diabetes case management program, as recommended by the ADA [24]. Another explanation may be that these patients do have a typical clinical presentation, despite having additional reasons for abdominal pain. This is supported by our findings, with 93% of children having an Alvarado's score ≥5, indicating compatibility with the diagnosis of appendicitis [8]. One important exception between diabetic and nondiabetic children was that most of the diabetic children in our series did not present with fever. This finding is corroborated by the 1988 report [11] and is distinctly different from what other investigators have reported regarding appendicitis in the pediatric population [7]. It is not clear why the diabetic children in our study so infrequently presented with fever. One explanation may be a relative immunodeficiency associated with DM in pediatric patients. While our patients, like most children with appendicitis [25], typically presented with leukocytosis suggesting an augmented immune response, there is some evidence to support that diabetic children are relatively immune deficient. Previous work has reported decreased levels of IgG and C4B in pediatric patients with DM, and hyperglycemia has been shown to impair cytokine production [26,27]. The absence of postoperative infectious complications in our cohort was reassuring, however, and was also supported by the 1988 report [11]. An alarming and perhaps the most important finding from our study was the poor postoperative glucose control our patients experienced, especially since this issue was anticipated and treated with multiple strategies. While no child in this study presented with or developed DKA, all children experienced significant postoperative hyperglycemia exceeding ADA and ISPAD recommendations for postoperative glucose control [10,28]. This is particularly concerning since recent evidence shows that children, like adults, suffer worse outcomes related to hyperglycemia [29–35]. Given the size of our study, it is difficult to determine if the lack of tight glucose control affected any of our patient's outcomes. What our series does demonstrate is that adequate postoperative glucose control in diabetic children with appendicitis is challenging and
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that these children require individualized glucose management. It is important for every surgeon to recognize that type 1 diabetics require continuous insulin therapy, generally with a long acting insulin or insulin pump basal rate, despite NPO status to prevent DKA [28]. During this period, blood glucose should be checked every 2–4 hours. It is recommended that the short acting insulin be given to correct hyperglycemia every four hours when a patient is NPO. More frequent dosing of short acting insulin can result in “stacking”, or excess insulin. Less frequent dosing can leave the patient in an insulin deficient state. Further, to optimize each patient's glucose management, we recommend consulting the pediatric endocrinology team or speaking with the patient's diabetes management provider to help coordinate care as soon as the surgical diagnosis is recognized.
References [1] Ogden CL, Carroll MD, Kit BK, et al. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999–2010. JAMA 2012;307:483–90. [2] Troiano RP, Flegal KM. Overweight children and adolescents: description, epidemiology, and demographics. Pediatrics 1998;101:497–504. [3] Sorof JM, Lai D, Turner J, et al. Overweight, ethnicity, and the prevalence of hypertension in school-aged children. Pediatrics 2004;113:475–82. [4] Pettitt DJ, Talton J, Dabelea D, et al. Prevalence of diabetes mellitus in U.S. youth in 2009: The SEARCH for Diabetes in Youth Study. Diabetes Care 2014;37:402–8. [5] Rosenbloom AL, Joe JR, Young RS, et al. Emerging epidemic of type 2 diabetes in youth. Diabetes Care 1999;22:345–54. [6] Anderson JE, Bicker SW, Chang DC, et al. Examining a common disease with an unknown etiology: trends in epidemiology and surgical management of appendicitis in California, 1995–2009. World J Surg 2012;36:2787–94. [7] Bundy DG, Byerley JS, Liles EA, et al. Does this child have appendicitis? JAMA 2007; 298:438–51. [8] Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med 1986;15:557–64. [9] Tsai SH, Hsu CW, Chen SC, et al. Complicated acute appendicitis in diabetic patients. Am J Surg 2008;196:34–9. [10] American Diabetes Association. Standards of Medical Care in Diabetes—2013. Diabetes Care 2013;36:S11–66. [11] Latchaw LA, Nguyen L. Acute appendicitis in diabetic children. Am J Dis Child 1988; 142:1019–20. [12] Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin dependent diabetes mellitus. N Engl J Med 1993;329:977–86. [13] Boland EA, Grey M, Oesterle A, et al. Continuous subcutaneous insulin infusion: a new way to lower risk of severe hypoglycemia, improve metabolic control, and enhance coping in adolescents with type 1 diabetes. Diabetes Care 1999;22: 1779–84. [14] Peña BM, Taylor GA, Lund DP, et al. Effect of computed tomography on patient management and costs in children with suspected appendicitis. Pediatrics 1999;104: 440–66. [15] el Ghoneimi A, Valla JS, Limonne B, et al. Laparoscopic appendectomy in children: report of 1,379 cases. J Pediatr Surg 1994;29:786–9. [16] Undeland KA, Hausken T, Svebak S, et al. Wide gastric antrum and low vagal tone in patients with diabetes mellitus type 1 compared to patients with functional dyspepsia and healthy individuals. Dig Dis Sci 1996;41:9–16. [17] Fraser RJ, Horowitz M, Maddox AF, et al. Hyperglycaemia slows gastric emptying in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1990;33:675–80. [18] Holiner I, Haslinger V, Lutschg J, et al. Validity of the neurological examination in diagnosing diabetic peripheral neuropathy. Pediatr Neurol 2013;49:171–7. [19] Umpierrez G, Freire AX. Abdominal pain in patients with hyperglycemic crises. J Crit Care 2002;17:63–7. [20] Pound N, Sturrock NDC, Jeffcoate WJ. Age related changes in glycated haemoglobin in patients with insulin-dependent diabetes mellitus. Diabet Med 1996;13:510–3. [21] Kakleas K, Kandyla B, Karayianni C, et al. Psychosocial problems in adolescents with type 1 diabetes mellitus. Diabetes Metab 2009;35:339–50. [22] Cheong LH, Emil S. Outcomes of pediatric appendicitis: an international comparison of the United States and Canada. JAMA Surg 2014;149:50–5. [23] Papandria D, Goldstein SD, Rhee D, et al. Risk of perforation increases with delay in recognition and surgery for acute appendicitis. J Surg Res 2013;184:723–9. [24] Silverstein J, Klingensmith G, Copeland K, et al. for the American Diabetes Association. Care of children and adolescents with type 1 diabetes: a statement of the American Diabetes Association. Diabetes Care 2005;28:186–212. [25] Kharbanda AB, Cosme Y, Liu KL, et al. Discriminative accuracy of novel and traditional biomarkers in children with suspected appendicitis adjusted for duration of abdominal pain. Acad Emerg Med 2011;18:567–74. [26] Reinhold D, Ansorge S, Schleicher ED. Elevated glucose levels stimulate transforming growth factor-beta 1 (TGC-beta 1), suppress interleukin IL-2, IL-6, and IL-10 production and DNA synthesis in peripheral blood mononuclear cells. Horm Metab Res 1996;28:267–70. [27] Liberatore Jr RR, Barbosa SF, Alkimin Md, et al. Is immunity in diabetic patients influencing the susceptibility to infections? Immunoglobulins, complement and
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[28] [29] [30]
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C.L. Stewart et al. / Journal of Pediatric Surgery 49 (2014) 1719–1722 phagocytic function in children and adolescents with type 1 diabetes mellitus. Pediatr Diabetes 2005;6:206–12. Betts P, Bring S, Silink M, et al. Management of children and adolescents with diabetes requiring surgery. Pediatr Diabetes 2009;10:169–74. Shuang SC, Lee KT, Chang WT, et al. Risk factors for wound infection after cholecystectomy. J Formos Med Assoc 2004;103:607–12. Zerr KJ, Furnary AP, Grunkemeier GL, et al. Glucose control lowers the risk of wound infection in diabetics after open heart operations. Ann Thorac Surg 1997;63:356–61. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med 2001;345:1359–67.
[32] Wintergerst KA, Buckingham B, Gandrud L, et al. Association of hypoglycemia, hyperglycemia, and glucose variability with morbidity and death in the pediatric intensive care unit. Pediatrics 2006;118:173–9. [33] Wu Y, Pei J, Yang XD, et al. Hyperglycemia and its association with clinical outcomes for patients in the pediatric intensive care unit after abdominal surgery. J Pediatr Surg 2013;48:801–5. [34] Saadat SMS, Bidabadi E, Saadat SNS, et al. Association of persistent hyperglycemia with outcome of severe traumatic brain injury in pediatric population. Childs Nerv Syst 2012;28:1773–7. [35] Gore DC, Chinkes D, Heggers J, et al. Association of hyperglycemia with increased mortality after severe burn injury. J Trauma 2001;51:540–4.
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Characterization of acute appendicitis in diabetic children Camille L. Stewart a,b,⁎, Colleen L. Wood a,c, John F. Bealer a,b a b c
Department of Surgery, University of Colorado School of Medicine, Aurora CO, United States Division of Pediatric Surgery, Children's Hospital Colorado, Aurora, CO, United States Division of Pediatric Endocrinology, Children's Hospital Colorado, Aurora, CO, United States
a r t i c l e
i n f o
Article history: Received 18 August 2014 Accepted 5 September 2014 Key words: Diabetes Appendicitis
a b s t r a c t Purpose: Children with diabetes mellitus (DM) who develop acute appendicitis can present a diagnostic and clinical challenge. No studies have examined this population since the advent of multiple dose insulin therapy, computed tomography, and laparoscopic surgery. We sought to characterize these children to identify their differences and how to best care for them. Methods: We retrospectively examined the medical records of children with a preexisting diagnosis of DM treated for acute appendicitis. Values are presented as the mean ± the standard error of the mean, and Student's t-test was used for statistical comparison. Results: We identified 18 diabetic children treated for acute appendicitis, making this the largest series of its kind. These children had similar presentations compared to non-diabetics, with the exception of often presenting without fever (83.3% with an initial temperature b 38 C). All children developed significant postoperative hyperglycemia (average high 382 ± 18 mg/dL), and most had glycemic control for ≤50% of the hospitalization (14/18, 77.8%), but they otherwise had typical postoperative courses. Conclusions: Diabetic children with appendicitis are often afebrile at presentation and have serum glucose levels that are difficult to control. Collaboration with pediatric endocrinologists is needed to appropriately manage these children during their hospitalization. © 2014 Elsevier Inc. All rights reserved.
Conventional clinical wisdom has historically held that differing disease processes occurring simultaneously are rare in children. Contemporary realities are changing given that children are becoming more adult-like in their development of chronic diseases such as obesity [1,2], hypertension [3], and diabetes mellitus (DM) [4,5]. Surprisingly, there is a paucity of literature regarding children with acute surgical illnesses and concomitant chronic disease. Appendicitis is a common surgical disease that frequently affects children and adolescents [6]. A typical constellation of signs, symptoms, laboratory, and radiologic tests are used to diagnose and determine management of these often otherwise healthy patients [7,8]. The diagnosis of appendicitis becomes more difficult in children with other medical problems, including DM. While it is known that adult diabetics with appendicitis have inferior outcomes [9], little is known about their pediatric counterparts. Given recent increased interest in glucose control and its relationship to morbidity and mortality in critically ill and surgical patients, we believe that it is important to improve our understanding of diabetic children who develop appendicitis.
preexisting diagnosis of DM that were subsequently treated for acute appendicitis from 2003 to 2013. All children in this cohort received diabetic care within a specialized diabetic program managed by pediatric endocrinologists. Information collected included basic demographics and clinical information regarding diabetic control, presentation, diagnosis, and postoperative care. Leukocytosis was defined as a white blood count (WBC) N10 × 10 3/μL. Diabetes compliance was defined based on the most recent hemoglobin A1c prior to the development of appendicitis, with a goal value b 8% for children 6–12 years old, and b7.5% for children 13–19 years old [10]. Glucose was considered controlled during hospitalization for values ≤ 180 mg/dL. Glycemic control is reported as the percentage of glucose checks ≤ 180 mg/dL compared to the total number of glucose checks during the hospitalization. Alvarado's score was calculated according to his original manuscript [8]. Study variables were available for all children except where noted otherwise. Continuous variables are presented as the mean ± the standard error of the mean, and Student's t-test was used to compare continuous variables.
1. Methods 2. Results After obtaining approval from our institutional review board, we retrospectively examined the medical records of children with a
2.1. Demographics
⁎ Corresponding author at: Department of Surgery, University of Colorado School of Medicine, 12631 E. 17th Ave., C302, Aurora, CO 80045, United States. Tel.: +1 720 777 4612; fax: +1 303 724 2682. E-mail address: [email protected] (C.L. Stewart).
We identified 18 children with DM who were treated for acute appendicitis. Demographic information is reported in Table 1. The average age at diagnosis of appendicitis was 11.9 ± 0.8 years (range
http://dx.doi.org/10.1016/j.jpedsurg.2014.09.003 0022-3468/© 2014 Elsevier Inc. All rights reserved.
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C.L. Stewart et al. / Journal of Pediatric Surgery 49 (2014) 1719–1722
Table 1 Demographics and presenting signs/symptoms of diabetic children with appendicitis. Qualifier Demographics Age (yrs) Duration of DM (yrs) Male Hx of noncompliance Hx of DKA Presenting symptoms/signs Abdominal pain Nausea/vomiting Diarrhea Fever N38 °C Tachycardia N100 BPM Leukocytosis N10 × 103/μL
Avg or N (STE or %) 11.9 (0.8) 3.7 (0.8) 11 (61.1%) 14 (77.8%) 3 (16.7%) 18 (100%) 16 (88.9%) 55 (27.8%) 3 (16.7%) 12 (66.7%) 15 (88.2%) Fig. 1. Diabetic children with appendicitis grouped by Alvarado's number.
7.2–19.0 years) and the average duration of diabetes was 3.7 ± 0.8 years (range 26 days–12.7 years). There were 11 males and 7 females, and all but one child had type 1 DM. Five children (27.7%) managed their blood glucose with an insulin pump. The other type I diabetics were treated with multiple daily injection therapy using both short and long acting insulins, and the only type II diabetic was treated with Metformin alone. The majority of children (77.8%) had a history of noncompliance based on their most recent hemoglobin A1c values, and 16.7% had a history of diabetic ketoacidosis (DKA). None of the children had a history of chronic abdominal pain, and 1 child had previous abdominal surgery.
and 17/18 (94.4%) appendectomies were performed laparoscopically. Perforation was found in 6/18 (33.3%) children. One child had a normal appendix with an appendicolith. Intra-operatively, most of the children (11/17, 64.7%) received no special or specific management of their serum glucose other than monitoring. Only one child received a bolus of insulin intra-operatively. All children with insulin pumps maintained basal insulin infusion during surgery except one whose pump insertion site was in the operative field.
2.2. Presentation
Pediatric endocrinology aided in glucose management for the majority of our patients (13/18, 72.2%). Children who managed their diabetes with a pump continued to do so postoperatively, and generally managed their insulin administration independently. Most stayed on their home basal insulin rate, with adjustments of 10-20% above or below basal rate for hyper or hypoglycemia, respectively. The rest of the children were managed with insulin for blood sugar correction and carbohydrate coverage postoperatively. This was often similar to their home regimen, with long-acting insulin in the morning and/or evening, and a fast acting insulin administered with meals to correct hyperglycemia and to cover carbohydrate consumption. When the endocrinology service was involved, they often adjusted these regimens according to prior blood glucose measurements. Every child in this study experienced hyperglycemia postoperatively, with an average peak serum level of 382 ± 18 mg/dL (range 262–551 mg/dL). Most children (14/18, 77.8%) had glucose levels controlled ≤50% of their hospitalization. Glucose control was similar for children with and without perforation (37% ± 4% versus 36% ± 8%, p = 0.98), and for those with and without an insulin pump (45 ± 10% versus 34 ± 6%, p = 0.34). Children whose management was aided by the pediatric endocrinology team had lower peak glucose values (375 ± 18 versus 402 ± 50 mg/ dL), but this difference was not statistically different (p = 0.54). Most children (15/18, 83.3%) had their diet advanced to a diabetic regular diet within one day of surgery. Glucose checks and short acting insulin administration were then generally adjusted to only before meals and at bedtime. The average length of stay was 3.2 ± 0.7 days, which was significantly longer for children with perforated (5.9 ± 1.4 days) compared to nonperforated appendicitis (1.8 ± 0.3 days, p = 0.001). No child developed DKA during their hospitalization, suffered from wound complications, or developed a postoperative abscess, and no child was readmitted with the exception of one child who received an interval laparoscopic appendectomy after initial drainage of an abscess.
Presenting signs and symptoms are presented in Table 1. The history of present illness included abdominal pain (100%), nausea/vomiting (88.9%), diarrhea (27.8%), and dysuria (5.6%). Ten children (55.6%) described the classic migration of pain to the RLQ, and 8 (44.4%) had rebound tenderness on exam. Children presented on average 3.6 ± 1.6 days after the onset of symptoms. Deviations in typical diabetic management or issues with glucose control after the onset of symptoms were only reported in 6/18 (33.3%). Only 3/18 (16.7%) children were febrile with a temperature N38 °C at presentation (average temperature 37.2 ± 0.2). Tachycardia (average heart rate 110.6 ± 6.5) was a commonly noted physical finding, seen in 12/18 (66.7%) of patients. WBC was measured in 17/18 children, and leukocytosis (average WBC count 15.1 ± 0.9) was found in the majority (15/17, 88.2%). The average presenting serum glucose was 188 ± 16 (range 85–306). Of the 10 children who had a urinalysis performed on presentation, 7/10 had excess glucose detected, and 7/10 had ketones detected. No child was acidotic on presentation, although objective evidence of acid/base status was not uniformly measured. The average bicarbonate was 21 ± 1 (n = 10, range 18–25), the average pH was 7.43 ± 0.02 (n = 5, range 7.39-7.49) and the average base deficit was 0.3 ± 0.6 (n = 5, range − 2 to 1.4). We were able to calculate Alvarado's score [8] for 15 children; all but 1 had a score ≥5 (Fig. 1). 2.3. Diagnosis and treatment All patients had imaging studies, either a CT scan (14/18, 77.8%) or ultrasound (4/18, 22.2%) of the abdomen, to assist in making the diagnosis of appendicitis. While nil per os (NPO), children without a pump continued to received their long acting insulin such as glargine (trade name: Lantus) for glucose control. Those with a pump continued to receive insulin at the basal setting. Metformin was held for the type II diabetic patient because of the risk of lactic acidosis. Blood glucose was checked every 2–4 hours, and treated with short acting insulin such as lispro (trade name: Humalog). The majority of children were treated with appendectomy within 24 hours of presentation (16/18, 88.9%),
2.4. Postoperative management
3. Discussion This study began by asking if diabetic children with acute appendicitis differed from nondiabetic children in their presentation, treatment,
C.L. Stewart et al. / Journal of Pediatric Surgery 49 (2014) 1719–1722
or outcomes. A literature search revealed a single previous study from 1988 characterizing diabetic children with appendicitis [11]. The relevance of this work to today's patients is limited since treatment has changed dramatically in the interim; multiple daily injections of insulin [12], continuous insulin infusion pumps [13], the widespread use of imaging for the diagnosis of appendicitis [14], and laparoscopic appendectomy [15] all are currently routine and have dramatically impacted the care of these patients. In this study we collected the largest cohort of diabetic children with appendicitis ever reported to update their clinical characteristics and facilitate their surgical care. Appendicitis is the most common surgical disease of the abdomen, and most commonly affects children during the second decade of life [6]. Diagnosis remains a significant clinical challenge demanding full consideration of a patient''s clinical signs, symptoms, laboratory findings, and imaging [7]. Abdominal pain is a nearly universal symptom of appendicitis but unfortunately, appendicitis is not a universal cause of childhood abdominal pain [7]. Many other common illnesses produce abdominal pain, and this is particularly true in children with other medical issues such as DM. Children with DM often suffer from abdominal pain [16], which can be caused by impaired gastric emptying related to hyperglycemia or neuropathy [17,18]. Abdominal pain is also a common symptom in DKA [19]. DKA is more common in diabetic adolescents, who frequently have poor glycemic control related to psychosocial and compliance issues [20,21]. This suggests that appendicitis in children with DM could pose a particular diagnostic challenge. Overall, children typically have some delay in surgical care and a higher rate of appendix perforation compared to adults [22,23]. While we do not have a direct control group for comparison, we were surprised to find that the duration of symptoms and perforation rate of our diabetic appendicitis patients were within the reported ranges for nondiabetic children with appendicitis [22,23]. It is possible that these children had improved or facilitated access to medical care from managing their DM prior to developing appendicitis. All the children in our series were part of an intensive diabetes case management program, as recommended by the ADA [24]. Another explanation may be that these patients do have a typical clinical presentation, despite having additional reasons for abdominal pain. This is supported by our findings, with 93% of children having an Alvarado's score ≥5, indicating compatibility with the diagnosis of appendicitis [8]. One important exception between diabetic and nondiabetic children was that most of the diabetic children in our series did not present with fever. This finding is corroborated by the 1988 report [11] and is distinctly different from what other investigators have reported regarding appendicitis in the pediatric population [7]. It is not clear why the diabetic children in our study so infrequently presented with fever. One explanation may be a relative immunodeficiency associated with DM in pediatric patients. While our patients, like most children with appendicitis [25], typically presented with leukocytosis suggesting an augmented immune response, there is some evidence to support that diabetic children are relatively immune deficient. Previous work has reported decreased levels of IgG and C4B in pediatric patients with DM, and hyperglycemia has been shown to impair cytokine production [26,27]. The absence of postoperative infectious complications in our cohort was reassuring, however, and was also supported by the 1988 report [11]. An alarming and perhaps the most important finding from our study was the poor postoperative glucose control our patients experienced, especially since this issue was anticipated and treated with multiple strategies. While no child in this study presented with or developed DKA, all children experienced significant postoperative hyperglycemia exceeding ADA and ISPAD recommendations for postoperative glucose control [10,28]. This is particularly concerning since recent evidence shows that children, like adults, suffer worse outcomes related to hyperglycemia [29–35]. Given the size of our study, it is difficult to determine if the lack of tight glucose control affected any of our patient's outcomes. What our series does demonstrate is that adequate postoperative glucose control in diabetic children with appendicitis is challenging and
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that these children require individualized glucose management. It is important for every surgeon to recognize that type 1 diabetics require continuous insulin therapy, generally with a long acting insulin or insulin pump basal rate, despite NPO status to prevent DKA [28]. During this period, blood glucose should be checked every 2–4 hours. It is recommended that the short acting insulin be given to correct hyperglycemia every four hours when a patient is NPO. More frequent dosing of short acting insulin can result in “stacking”, or excess insulin. Less frequent dosing can leave the patient in an insulin deficient state. Further, to optimize each patient's glucose management, we recommend consulting the pediatric endocrinology team or speaking with the patient's diabetes management provider to help coordinate care as soon as the surgical diagnosis is recognized.
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