UNIVERSITY OF CALIFORNIA, IRVINE Intravenous Acetaminophen: A Non-Narcotic Adjunct for Burn Wound Care THESIS submitted in partial satisfaction of the requirements for the degree of MASTER OF SCIENCE In Biomedical and Translational Science by Sarah Dobson Thesis Committee: Professor Sherrie H. Kaplan, Chair Assistant Clinical Professor Nicole P. Bernal Associate Clinical Professor Steven Mills 2014 © 2014 Sarah Dobson TABLE OF CONTENTS Page LIST OF FIGURES………………………………………………………...………………….v LIST OF TABLES…………………………………………………………..…….……………vi ACKNOWLEDGEMENTS…………………………………………………………………….vii ABSTRACT OF THE THESIS…………………………………………...………….............viii CHAPTER 1: INTRODUCTION………………………………………………..…………….1 CHAPTER 2: BACKGROUND………………………………………………………...……..3 Burn Wound Care…………………………………………………………….............3 Background versus Breakthrough Pain……………………………………............3 Narcotic Pain Medications…...…………………………………………..…………..4 Intravenous Acetaminophen…………………………………………...…………….5 First-pass Metabolism………………………………………………..……………....8 CHAPTER 3: METHODS……………………………………………………………….……9 Setting…………………………………………………………………..………...……9 Sample…………………………………………………………………………………9 Exclusion Criteria…………………………………………………………………….11 Study Design……………………………………………………………………....…13 Pain Measures…………………………………………………………………….…14 Outcome Measures………………………………………………………………….15 Organizing the Data……………………………………………...………………….16 Analyzing the Data………………………………………………...…………..…….17 Power Analysis…………………………………………………………………….…18 iii CHAPTER 4: RESULTS……………………………………………………….……………19 Demographics…………….……………………………………………..……...……19 Primary Outcome…………………………………………………………..………...21 Secondary Outcome………………………………………..……………………….22 Subgroup Analyses………………………………………………………………....23 CHAPTER 5: DISCUSSION………………………………………………….…………….26 Limitations……………………………………………………..……………….…….29 Proposal……………………………………...…………………………..…….…….30 REFERENCES………………………………………………………………………....……33 APPENDIX……………………………………………………………………………..…….35 iv LIST OF FIGURES Page Figure 1: Acetaminophen plasma concentration over time 7 Figure 2: Exclusion criteria flow chart 12 v LIST OF TABLES Page Table 1: Characteristics of intravenous versus oral acetaminophen 7 Table 2: Patient Demographics 19 Table 3A: Types of Injuries 20 Table 3B: Location of Injuries 20 Table 4: Amount of narcotics on total days with administration of IV 21 acetaminophen versus days without administration of IV acetaminophen Table 5: Liver Function Test scores of Alkaline Phosphatase, Aspartate 22 Aminotransferase and Alanine Aminotransferase Table 6: Amount of narcotics for days with IV acetaminophen versus 23 without IV acetaminophen for patients with <15% Total Body Surface Area and >15% Total Body Surface Area Table 7: Amount of narcotics for days with IV acetaminophen versus 24 days without IV acetaminophen for patients with a hospital Length of stay of <7 days and >7 days Table 8: Amount of narcotics for days with IV acetaminophen versus 25 days without IV acetaminophen for patients with flame/flash burns and with non-flame/flash burns vi ACKNOWLEDGEMENTS I would like to express my appreciation to my committee chair, Dr. Sherrie H. Kaplan, for not only her knowledge in various subjects, but for her guidance throughout this program and project. I want to also thank her for all of her hard work and dedication in making this Master’s program as prestigious and well-rounded as it is now. I was honored to have her serve as the chair of my committee and for her endless advice and encouragement. She has helped me in learning how to endure constructive criticism as well as which steps to take to be successful in this program and in my future endeavors. I also want to thank my committee member and mentor, Dr. Nicole Bernal, for her support throughout my research career and throughout this program. I would like to thank her for her continuous mentorship and guidance. I am a better student and researcher because of what she taught and showed me. I would like to thank Dr. Steven Mills for his advice and informative recommendations. His support was crucial in helping to develop the guidelines for this project to critiquing the final draft. His advice on the specifics of analysis helped to better the project and provide more comprehensive and reliable data. I’d like to thank my professor, Dr. John Billimek for his endless statistics advice. He was a wonderfully inspiring teacher who went above and beyond in the effort to make sure I had a firm grasp of the methodologies for capturing, organizing and evaluating the data sets used in this study. vii ABSTRACT OF THE THESIS Intravenous Acetaminophen: A Non-Narcotic Adjunct for Burn Wound Care By Sarah Dobson Master of Science in Biomedical and Translational Science University of California, Irvine, 2014 Professor Sherri H. Kaplan, Chair Burn injury is the cause of one of the most severe types of pain. Many studies have shown that burn pain management is inadequate in most burn centers. Multiple studies have shown that intravenous acetaminophen decreases the overall amount of narcotics administered as well as longer time until drug rescue. Intravenous acetaminophen can be incorporated into the multi-modal approach in order to reduce the amount of narcotic pain medications administered so that pain can be controlled more safely and effectively. This retrospective study analyzed demographic characteristics, amount of narcotics administered on days with and without administration of intravenous acetaminophen prior to burn wound care and effects of multiple doses of intravenous acetaminophen in hepatic function. Forty one patients admitted to the University of California, Irvine Burn Center between August 2011 and August 2013 were included in the sample. Comparing the average amount of narcotics administered on days with administration of IV acetaminophen showed no statistically significant difference when viii compared with amount of narcotics on days with no administration of IV acetaminophen. After performing subgroup analyses, there were reductions found in amount of narcotics on days when IV acetaminophen was administered. However, these reductions were not statistically significant. There was no deterioration in hepatic function after one or more doses of 1,000mg of intravenous acetaminophen throughout all of the 41 patient’s hospital stays. The results demonstrated the effectiveness of intravenous acetaminophen in certain groups. On the other hand, there were also groups in which intravenous acetaminophen was clearly ineffective. Furthermore, it has been shown that IV acetaminophen does not cause any potential health risks to the liver. The results of this study, in particular the subgroup analyses, may warrant further evaluation in a prospective, controlled setting. A prospective study would be used to determine whether the use of IV acetaminophen as an adjunct to use of increased dosages of narcotics during burn wound care will provide more effective and consistent pain relief to a larger segment of patients in a burn unit. ix CHAPTER 1: INTRODUCTION Burn injury is the cause of one of the most severe types of pain as well as physical and psychological distress (Abdi, Zhou, 2002). Many recent studies have shown that burn pain management is inadequate in most burn centers. (Latarget, 2002). The two main reasons for poor burn pain control are: 1) the intensity of pain associated with burn wound care varies greatly throughout the hospital stay, which makes pain medication requirements difficult to approximate for the same patient, and 2) there is a lack of knowledge and education by the staff, patients and families concerning the distinctive characteristics of pain experienced by burn patients (Gregoretti, et al., 2008). If the pain caused from a burn injury is not adequately controlled, there is a greater chance of psychological problems. (Gregoretti, et al., 2008). These problems can occur because of the subsequent anxiety due to their pain, which may lead to the lengthening of the stress response after a burn injury, prolonging the healing of wounds and extending the recovery time. (Byers, et al., 2001, Guyton, 1997, Monafo, 1995). It has been shown that anxiety is not only a factor of pain, but anticipatory anxiety increases pain during dressing changes. (Ashburn, 1995). In order to prevent the development of any psychological problems, a multi-modal approach is necessary in the treatment of burn pain. A multi-modal approach is defined as administering a combination of drugs, each having various pharmacological properties, which may allow for a reduction in the total dosage of single drugs, potentially avoiding adverse events. (Gregoretti et al., 2008). The multi-modal approach focuses on treating the different aspects of pain, which includes direct pain, neurogenic pain and anxiety. Unfortunately, all of these medications can affect cognition and respiratory status. Treating pain 1 through the use of medications that may have a negative effect on respiration or alter mental status led to the exploration of use of intravenous acetaminophen. The aim of this study was to identify if: 1) intravenous acetaminophen administered as a pre-medication for wound care reduced the overall amount of intravenous narcotic pain medications administered during wound care, and 2) after one or more doses of 1,000 mg per day of intravenous acetaminophen, it would not result in an adverse effect on liver function. Along with utilizing the multi-modal approach, pain needs to be evaluated frequently in order to control pain effectively during burn