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A Systematic Review and Meta-Analysis of Intravenous Sedation in Modern Cataract Surgery

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A Systematic Review and Meta-Analysis of Intravenous Sedation in Modern Cataract Surgery Western University Scholarship@Western Electronic Thesis and Dissertation Repository 10-27-2017 3:00 PM A Systematic Review and Meta-Analysis of Intravenous Sedation in Modern Cataract Surgery Efstathia Kiatos The University of Western Ontario Supervisor Dr. Monali Malvankar The University of Western Ontario Co-Supervisor Dr. William Hodge The University of Western Ontario Graduate Program in Epidemiology and Biostatistics A thesis submitted in partial fulfillment of the equirr ements for the degree in Master of Science © Efstathia Kiatos 2017 Follow this and additional works at: https://ir.lib.uwo.ca/etd Recommended Citation Kiatos, Efstathia, "A Systematic Review and Meta-Analysis of Intravenous Sedation in Modern Cataract Surgery" (2017). Electronic Thesis and Dissertation Repository. 4982. https://ir.lib.uwo.ca/etd/4982 This Dissertation/Thesis is brought to you for free and open access by Scholarship@Western. It has been accepted for inclusion in Electronic Thesis and Dissertation Repository by an authorized administrator of Scholarship@Western. For more information, please contact [email protected]. i Abstract Phacoemulsification is a surgical technique in which a cataract is extracted and replaced with an intraocular lens implant. This can be done under intravenous sedation, oral sedation, or no sedation, in addition to local anesthetic techniques. The purpose of this systematic review and meta-analysis is to assess the effectiveness of intravenous sedation versus non-intravenous sedation methods. Results found that intravenous sedation was significantly associated with a decrease in pain when compared to non- intravenous methods (SMD = -0.86, 95% CI 1.49 to -0.23, p=0.0008) (WMD = -1.01, 95% CI -1.66 to -0.36, p=0.002). The subgroup analysis found patients did not have a statistically significant reduction in pain when using intravenous sedation over oral sedation. The meta-analysis of perioperative complications found that intravenous sedation did not have a statistically significant increase in adverse events when compared to non-intravenous anesthesia techniques. These findings could inform policy and help develop definitive guidelines for sedation and anesthesia strategies during phacoemulsification. Keywords Cataract, cataract surgery, phacoemulsification, intravenous sedation, sublingual sedation, pain, complications, ophthalmology, systematic review, meta-analysis ii Co-Authorship Statement The work presented in this document was performed entirely by the author. The only exceptions were the literature search, level 1 and 2 screening, data extraction, the risk of bias assessment, and quality assessment. The search strategy was created with the help of Dr. John Costella, who was the librarian on my project. For level 1 and 2 screening, James Jacob Armstrong (JJA) was the second reviewer alongside myself (EK). For data extraction, risk of bias assessment, and quality assessment, Stephen Tsioros (ST) was the second reviewer and I (EK) was the first reviewer. Discrepancies between any of the processes were solved by Dr. William Hodge (WGH). iii Dedication This thesis is dedicated to the loving memory of my grandfather, Efstathios Patsas, who I still miss every day. Thank you to my family for their unconditional love and constant support. iv Acknowledgements First, I would like to thank the Department of Epidemiology and Biostatistics at Western University for providing me with an excellent education that fosters academic achievement. The course work, although demanding, gave me a thorough understanding of epidemiology and biostatistics, and allowed me to complete this document. Thank you to the faculty and staff for their continuous understanding and support through my graduate school experience. A big thank you to Dr. William Hodge, who supervised me throughout this journey. I cannot express the gratitude I feel for all the opportunities you have given me. The countless hours of advice and help with multiple research projects which allowed me to complete this thesis. Thank you to Dr. Cindy Hutnik who also supervised my thesis project. You not only took me under your wing when I was feeling lost, but inspired me and pushed me to succeed. I am extremely grateful for the opportunities and advice you have given me. Dr. Hodge and Dr. Hutnik have not only been amazing advisors, but are lovely people and I have truly enjoyed my time with them. I would like to thank my friends in my MSc cohort, especially Catherine, Misbah, Patrick, and Alex. The four of you have kept me sane throughout this whole process and have given me a lifetime of memories and laughs. From staying up all night in Kresge working on assignments, to helping each other with our thesis documents, the friendship and teamwork we shared is unforgettable. Finally, I would like to thank Chris for constantly encouraging me throughout this entire process, and always believing in me. v Table of Contents List of Tables viii List of Figures ix List of Appendices x List of Abbreviations xi CHAPTER 1 Introduction & Thesis Objectives 1 1.1. Financial Cost of Cataracts 1 1.2. Cataracts & Treatment 3 1.3. Perioperative Anesthesia Techniques Associated with Cataract Surgery 4 1.4. Thesis Rationale 5 1.5. Thesis Objectives 6 1.6. Structure of Thesis Document 6 CHAPTER 2 Literature Review 8 2.1. Introduction 8 2.2. Classification of Cataracts 8 2.3. Symptoms of Cataracts 9 2.4. Etiology 10 2.5. Epidemiology 12 2.6. Treatment 14 2.7. A Brief History of Cataract Surgery 14 2.8. Fundamentals of Modern Phacoemulsification 16 2.9. Introduction to Anesthesia and Sedation Strategies 18 2.9.1. Conscious Sedation 18 2.9.2. Central Nervous System Medications via Intravenous Therapy 21 2.9.3. Cost of Various Anesthesia Management Strategies 22 2.9.4. Topical and Regional Anesthetic Techniques 23 2.9.5. General Anesthesia 26 2.10. Ocular Complications from Cataract Surgery 26 2.11. Systemic Complications during Cataract Surgery 30 CHAPTER 3 Literature Review for Methodology 32 3.1. Introduction to Meta-Analysis 32 3.2. History of Meta-Analysis 32 3.3. Reasons to Conduct a Meta-Analysis 33 vi 3.4. True Effect Size, Observed Effect Size, and Summary Effect Size 35 3.5. Random Effects versus Fixed Effects 35 3.6. Heterogeneity 36 3.7. How to Measure Heterogeneity (I2) 37 3.8. Investigation of Heterogeneity 38 3.9. Statistical Principles of Meta-Analysis 39 3.10. Effect Measures for Dichotomous Outcomes 40 3.11. Effect Measures for Continuous Outcomes 41 3.12. Effect Measures for Count Data 42 3.13. Publication Bias – Funnel Plots 43 3.14. Missing Data 45 3.15. Risk of Bias Assessment 45 CHAPTER 4 Methods 47 4.1. Methods Introduction 47 4.2. Search Strategy 47 4.3. Eligibility Criteria 48 4.4. Article Screening 50 4.5. Data Extraction for Qualitative Data 51 4.6. Data Extraction for Quantitative Data 52 4.7. Risk of Bias in Included Studies 53 4.8. Risk of Bias versus Study Quality 54 4.9. Assessing Study Quality using GRADE 54 4.10. Data Analysis 55 CHAPTER 5 Results 57 5.1. Study Selection 57 5.2. Study Characteristics 58 5.3. Risk of Bias within Studies 60 5.4. GRADE Quality Assessment 61 5.5. Primary Outcome – Pain 63 5.5.1. Data Extraction and Imputation 63 5.5.2. Meta-Analysis – Standardized Mean Difference 64 5.5.3. Sensitivity Analysis 65 5.5.4. Meta-Analysis – Weighted Mean Difference 67 5.5.5. Sub-group Analysis by Intervention Sedation 68 vii 5.5.6. Sub-group Analysis by Non-Intravenous Sedation Method 70 5.5.7. Meta-regression 71 5.5.8. Funnel Plot 72 5.6. Primary Outcome – Complications 73 5.6.1. Meta-Analysis 74 5.6.2. Funnel Plot 76 CHAPTER 6 Discussion 77 6.1. Overview 77 6.2. Systematic Review 77 6.3. Meta-Analysis and Subgroup Analysis 78 6.4. Publication Bias 81 6.5. Limitations 81 6.6. Strengths 83 6.7. Recommendations for Future Research 84 6.8. Conclusion 84 Literature Cited 85 Appendices 100 Curriculum Vitae 116 viii List of Tables Table 2.1: Cost to Providers for Various Sedation Methods in Cataract Surgery .......... 22 Table 4.1: Concepts, Keywords, and Phrases for Search Strategy ............................... 48 Table 4.2: Study Eligibility Criteria .................................................................................. 51 Table 5.1: Demographic Characteristics of Included Studies ......................................... 58 Table 5.2: Intervention Characteristics of Included Studies ........................................... 59 Table 5.3: Participant Characteristics of Included Studies ............................................. 60 Table 5.4: GRADE Evidence Profile ............................................................................... 62 Table 5.5: Extracted Data for Meta-Analysis .................................................................. 63 Table 5.6: Random Effects Meta-Regression Results ................................................... 71 Table 5.7: Quantitative Data for Meta-Analysis .............................................................. 73 ix List of Figures Figure 1.1: Prevalence of Vision Loss by Cause .............................................................. 1 Figure 1.2: Total Financial Costs of Vision Loss in 2007 ................................................. 2 Figure 1.3: Direct Costs of Vision Loss Compared to Other Diseases ............................. 3 Figure 1.4: Anatomy of the eye and location of Cataract7 ................................................ 4 Figure 2.1: Cataract Classification ................................................................................... 9 Figure
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