DIABETES TECHNOLOGY & THERAPEUTICS Volume 16, Number 9, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/dia.2013.0388

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ORIGINAL ARTICLE

Insulin Pump–Associated Adverse Events in Children and Adolescents—A Prospective Study Benjamin J. Wheeler, MBCHB, DCH, CCE, FRACP,1,2 Kristine Heels, RN, CDE, MAppMgt,1 Kim C. Donaghue, MBBS, PhD, FRACP,1,3 David M. Reith, MBBS, MMedSc, PhD, DCH, DipRACOG, FRACP,2 and Geoffrey R. Ambler, MBBS, MD, FRACP1,3

Abstract

Background: Intensive insulin regimens are now the mainstay of modern, type 1 diabetes mellitus management. Insulin pumps (CSII) are a key technique used. Although there has been considerable study of outcomes, there are few recent data on CSII-associated adverse events (AEs) and their incidence and characteristics. Subjects and Methods: Phone calls to our 24-h diabetes support service were screened for CSII-associated AEs. Phone interviews were conducted with the parent/patient, within 96 h of the event. Interviews explored AE characteristics and the role of the user, as well as questions relating to outcome and the impact to the family and patient. Comparisons were made with clinic CSII patients not reporting an AE. Results: Over a 16-week study period, 50 confirmed AEs occurred in 45 of 405 (11.1%) patients. This was annualized to an AE incidence of 40 AEs/100 person-years. Pump malfunction and infusion set/site failures were the most common events reported, occurring in 27 (54.0%) and 18 (36.0%) AEs, respectively. A user- or education-related issue was implicated in 22 (44.0%) events. Pump replacement occurred in 19 of 50 occurrences (38.0%). Additionally, 16 (32.0%) reported a hospital admission or emergency department attendance as a consequence. When compared with those on CSII not reporting an AE, AEs were associated with age < 10 years (odds ratio = 3.2 [95% confidence interval, 1.7–6.1]) but not with gender, glycosylated hemoglobin, diabetes duration, or pumping duration. Conclusions: This is the first prospective study to look at AEs in modern-generation insulin pumps. AEs appear common and should be anticipated. Their origin is multifactorial, with the pump, associated consumables, and the user all being important factors. Ongoing support and anticipatory education are essential to minimize pump–associated AEs and their impact. Introduction

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ollowing landmark studies such as the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications,1,2 intensive insulin regimens have become the standard of care in both adults and children with type 1 diabetes mellitus. With this have come substantial improvements in insulin pump (continuous subcutaneous insulin infusion [CSII]) technology, and CSII now plays a prominent and increasing role in modern diabetes management. CSII offers a range of potential advantages over a regimen of multiple daily injections (MDI). Improvements in glycemic control, as measured by

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glycosylated hemoglobin (HbA1c), in the order of 0.2–0.5% (2.2–5.5 mmol/mol) are seen,3–5 along with benefits to quality of life in all studies assessing this as an outcome.5,6 Although in the past, contrasting data on the reduction of severe hypoglycemia have been seen,4,7 more recent studies support this as an additional advantage.5,8 In contrast to these advantages, there are minimal recent data on possible adverse events (AEs) or negative consequences. A recent retrospective study, using family/selfreported survey data, suggested an annual CSII AE rate of 45%.9 Pump malfunction followed by infusion set/site failures were the most common events reported. An event requiring total pump replacement and/or hospital attendance

The Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Sydney, Australia. Department of Women’s and Children’s Health, University of Otago, Dunedin, New Zealand. Discipline of Paediatrics and Child Health, The University of Sydney, Sydney, Australia.

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INSULIN PUMP–ASSOCIATED ADVERSE EVENTS

occurred in 23% and 8%, respectively. An earlier 1984 study, using very different technology from our current-generation CSII, found significant AEs, such as diabetic ketoacidosis (DKA), hypoglycemia, and skin infection, at a similar rate of 42% of subjects over an 18-month study period.10 Data on CSII AE reporting from the U.S. Food and Drug Administration have also recently been published.11,12 Again, as with the article from the 1980s, only more significant events such as DKA, hypoglycemia, and hospitalization are reported, and no information on incidence and true characteristics can be gleaned. It is interesting that in the minority of cases where pumps were able to be analyzed, many of those reported as ‘‘total pump failure’’ appeared to be working without fault. This finding highlights the potential importance of the user/ education in CSII-associated AEs. Insulin infusion sites are an additional vital component of CSII therapy. They have been examined in several studies. In one article, difficulties with sites were the precipitating reason for permanent pump discontinuation in 21%,13 with another study reporting cannula failure, resulting in premature cannula replacement in 8–9% of total insertions.14 With these issues in mind, to help characterize insulin pump–associated AEs and the role of the user in them, we conducted a prospective, interview-based study of all families reporting an insulin pump–related AE to our diabetes service over a 16-week period. Subjects and Methods

The diabetes team at the Children’s Hospital at Westmead, Sydney, Australia, cares for approximately 850 local children and adolescents with type 1 diabetes mellitus; of these, 405 are using CSII, with 99% on Medtronic (Northridge, CA) brand pumps. Their mean – SD HbA1c for the year ending 2013 was 8.4 – 1.4%. Prior to commencing CSII, they undergo a 3-month training period, including sessions with a multidisciplinary team composed of medical, diabetes educator, dietician, and psychology/social work services. Basic pump trouble shooting and disconnection dosing plans are given as part of education, including emergency contacts for our hospital 24-h, 7 days/week, medical phone support and 24-h technical support services provided by the relevant insulin pump manufacturers. Over a 16-week period, in June–October 2013 (winter– spring), data were prospectively collected on insulin pump– associated AEs. All phone calls to the diabetes team, both medical and diabetes nurse educator, were screened for potential CSII-associated AEs. As patients in this region of Sydney may also present to their local emergency department or family doctor/pediatrician, calls from these sources were also screened for CSII-associated AEs relating to our patients. As opposed to calls for patients on MDI, it is expected that the vast majority of these presentations would be phoned in, as Children’s Hospital at Westmead is the only insulin pump service in this region of Sydney. Calls were handled in the usual way by the 24-h diabetes on-call service, and then name and contact details for the family were passed on to the audit team, as part of a daily handover. Within a 96-h period following the original report, a follow-up telephone-based interview, in English, was conducted with the person reporting the initial event. Interviews were conducted by B.J.W. and K.H., with B.J.W. reviewing all interviews to

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ensure quality control. Data on the AE and factors leading to it, including timing of prior set/site changes, ketone testing, relevant blood glucose levels, any laboratory investigations, eventual outcome, and impact to the family, were collected. User contribution (present/not present) was also determined by qualitative analysis and deemed present only if clear contributing factors were seen. Specific factors leading to a conclusion of a user/education contribution were if the user did not follow recommendations for pump maintenance or timing of set changes, if there was an associated flat battery or physical or water damage, if there was inadequate monitoring leading to an AE (e.g., hypoglycemia), or if there was an inappropriate response to an AE that negatively impacted on outcome (e.g., delivering insulin correction via the pump in context of high ketones and hyperglycemia [presumed set/ site failure], leading to further deterioration). Finally, various potential psychosocial impacts to the family/patient were assessed. This was determined by qualitative analysis and parental self-report. Factors such as absence from school or work (yes/no), disruption to family plans and activities (yes/ no, plus qualitative analysis of specific details collected during interview), and associated significant stress to the child/parent (yes/no, determined by qualitative assessment of the interview, including self-report by direct questioning around the child’s and parent’s perceptions of associated stress as significant or not) were collected. All events were reviewed by B.J.W., K.H., and K.C.D. to determine user involvement, and classification was assigned only when there was universal agreement. If needed, a further phone interview was conducted to confirm the time to pump replacement or any other outcome not clear at the first interview. Basic demographic data and management were obtained from our hospital diabetes database and compared with the remainder of our CSII clinic patients (n = 360) not reporting an AE over this period. Hospital records were also examined in each instance for hospital/emergency department visits. Statistical analysis was conducted using STATA (StataCorp, College Station, TX) data analysis and statistical software. Age for subjects experiencing an event was bimodally distributed, and therefore age was transformed into three age categories using the distribution to determine the breakpoints. Associations between exposure variables and presence or absence of AE were tested using logistic regression. Risks were expressed as odds ratio (95% confidence interval). Ethics approval was provided by the Children’s Hospital at Westmead Clinical Governance Ethics Committee. Results

Over the 16-week study period, 54 notifications of potential AEs were received. Of these, in three the pump did not appear to have any role in the reported event, and in one instance the family was unable to be contacted to interview. This gave a final study total of 50 AEs, occurring in 45 individuals (five individuals experienced two separate AEs over the study period), 11.1% of the total clinic pump population of 405. This was annualized to an AE incidence of 40 AEs/100 person-years. Of the events, 19 of 50 (38%) resulted in pump replacement, or an estimated 15% of our pump patients per year. A user- or education-related issue was implicated in 22 of 50 (44%) events. Of these, 12 of 22 (59%)

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WHEELER ET AL.

were related to set/site failure, representing 12 of 18 (67%) of all set/site failures. Basic demographics of clinic CSII patients reporting an AE and those not reporting an AE are shown for comparison in Table 1. All events occurred in Medtronic Veo or X22 pumps, reflecting their 99% overall use in this clinic population. Four or more clinic visits in the previous 12 months were reported for 24 of 50 (48%) occurrences, versus 26 of 50 (52%) having three or fewer visits. A previous emergency department/hospital presentation was discovered in the past 12 months in nine of 50 (18%): of the nine, three were for hypoglycemia, three were for DKA, and three were for a non–diabetes-related illness. In addition to reporting the event to us, the insulin pump company had also been contacted by the family in 22 of 50 (44%) occasions. When compared with our control group, the occurrence of an AE was associated with age 50 (>100%) because multiple impacts could be selected for each event. b Required all three of the following: venous pH

Insulin pump-associated adverse events in children and adolescents--a prospective study.

Intensive insulin regimens are now the mainstay of modern, type 1 diabetes mellitus management. Insulin pumps (CSII) are a key technique used. Althoug...
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