Outcomes Research in Regional Anesthesia and Analgesia

Outcomes research evaluates the effectiveness of health care interventions in many aspects of patient care (clinical outcomes, functional health status, patient satisfaction, and economic measurements) and reflects national trends in determining the appropriateness, value, and quality of health care in the United States (1). Outcomes research incorporates diverse types of data and data analysis. Although outcomes measurements include a wide variety of patient-related assessments, anesthesiologists have traditionally focused on clinically related patient outcomes. Thebenefit of regional anesthesia on patient-related outcomes is controversial. Many questions involving study design, data analysis and sample size contribute to the uncertainty of the benefits of regional anesthesia-analgesia on patient outcomes. Like those from other subspecialties in anesthesiology, investigators evaluating the efficacy of regional anesthesia have emphasized traditional, clinically oriented, patient-related outcomes. Little has been done to determine the consequences of regional anesthesia and postoperative analgesia on “nontraditional” patient outcomes, such as health-related quality-of-life (HRQL) measurements, patient satisfaction, and economic assessments. This article provides an overview of outcomes research, the current status of outcomes research in regional anesthesia, and future directions for determining the benefits of regional anesthesia and postoperative analgesia. Outcomes Research: An Overview Substantial increases in health care costs have contributed to the development of outcomes research in the United States. Health care costs constitute a significant percentage of the gross national product (GNP) and have increased at a rate much greater than that of inflation or overall growth in GNP. Despite the high percentage of GNP spent on health care, the United States lags behind many other industrial nations in major indexes of health, such as life expectancy and infant mortality (1). These factors, along with the presence of significant geographical variations in clinical practice without differences in clinical outcomes, have resulted in political and economic pressures to reevaluate the appropriateness, value, and quality of health care in the United States (1). What Are “Outcomes”? Although “outcomes research” has become a popular topic for investigators, true outcomes research incorporates a wide variety of patient-related measurements, including those other than the more familiar clinically related assessments. In general, outcomes research involves an assessment of the effectiveness of a health care intervention on various aspects of patient benefits and includes not only clinical outcomes but also functional health status, patient satisfaction, and economic measurements (see Table 1) (1). Functional health status of a patient may be assessed by using validated instruments to measure quality-of-life, physical, psychologic, and social variables. There are few validated instruments to measure patient satisfaction with various aspects of anesthetic care, and patient satisfaction surveys must be carefully constructed and validated to ensure that specific health care interests are addressed (2). Economic measurements have become more prevalent in the anesthesia literature; however, there are a variety of economic analyses, each which may result in a different conclusion depending on the type and perspective (societal, patient, payer, provider) of analysis (3).Table 1: Types of Patient-Related Outcomes in Regional AnesthesiaTypes of Data and Data Analysis Many types of data and data analysis may be used in outcomes research. Although a detailed discussion of all types of data and data analysis is beyond the scope of this article, a brief description of those most relevant to the evaluation of the benefits of regional anesthesia on patient outcomes will be discussed to facilitate interpretation of results and conclusions derived from outcomes research studies (see Table 2).Table 2: Randomized, Controlled Trials Versus Databases for Research in Regional AnesthesiaProspective Data: Randomized, Controlled Trial. The randomized controlled trial (RCT) is considered by many to be the “gold standard” in evaluating the effect of an intervention on patient outcomes. Randomization minimizes the possibility that confounding factors may interfere with analysis of any potential association between risk factors and outcomes (4). By standardizing inclusion-exclusion criteria and treatment protocols, prospectively defining outcomes and using a placebo or accepted alternative treatment, a RCT maximizes the likelihood that outcomes obtained are the result of the intervention applied. Despite the strength of the RCT, it has several disadvantages, some of which are relevant when determining the effect and efficacy of regional anesthesia and analgesia on patient outcomes. Significant drawbacks to RCTs include the cost, time, and need for extremely large sample sizes when evaluating rare outcomes. For example, a sample size of 24,000 patients would be needed to determine if regional anesthesia would have a beneficial effect in decreasing the incidence of overall mortality by 50% (power of 80%) when compared with that from general anesthesia (5). Execution of such a study at one center would be extremely time consuming and expensive. Although multicenter trials are possible, protocol deviation and institutional differences may affect the study results. Furthermore, increasing sample size through multicenter trials may not necessarily improve statistical power (6). Other disadvantages of RCTs include ethical concerns and less external validity (applicability of the findings to a more heterogenous population). In addition, RCTs examining regional versus general anesthesia are necessarily unblinded (with exception of the Perioperative Ischemic Randomized Anesthesia Trial or PIRAT 2), allowing for the introduction of bias. Meta-analysis. Despite the increasingly common use of meta-analysis to combine and evaluate data from various sources, meta-analysis is relatively controversial. The effect of an intervention, such as regional anesthesia, on patient outcomes may be difficult to determine as a result of the need for extremely large sample sizes. Studies in these areas are, for the most part, underpowered and may yield conflicting results. Meta-analysis, which involves strict criteria for the inclusion of studies for analysis and statistical methods specific for this type of analysis, attempts to integrate and synthesize the results from several smaller trials. There are several disadvantages of meta-analysis, one of the most significant of which is the creation of results and conclusions based on nonoriginal data from studies that may vary in study design, subject population, and outcomes criteria. Although some may argue that the heterogeneity of data reflects random error, small differences in one of several factors may affect whether a trial is acceptable to include for analysis, thus potentially altering the final results and conclusions of the meta-analysis (7). Meta-analysis may also contain publication biases (exclusion of non-English languages trials and unpublished data) (8). Although meta-analysis may be a useful tool to synthesize data from a variety of sources, the analysis and conclusions from a meta-analyses must be carefully worded (and read) in an attempt to prevent oversimplifying a complex issue (7). Finally, conclusions from meta-analysis may not correlate with that from subsequent large-scale RCTs (7). Retrospective Data: Databases. With the availability of large administrative or insurance claims databases, there have been an increasing number of studies analyzing database information in outcomes research. Database analysis and data acquisition generally cost less and require less time when compared with equally large RCTs. Databases contain information from regional and national populations, which may facilitate assessment of small frequency outcomes. In addition, information from databases reflects typical clinical practice. However, databases are retrospective in nature, may contain missing data points, and may not accurately measure the outcomes of interest. In addition, the informational content reflects the purpose of the database (mostly billing and claims) which, despite the presence of demographic and diagnosis codes, may not necessarily be useful in outcomes research. Incomplete coding may also hinder data analysis and result from limitations in the number of available diagnostic or procedural coding slots (9). Thus, there may not be enough information available to answer the hypothesis posed. Finally, large databases may be “massaged” to obtain “significant” associations between risk factors and outcomes (10). Although databases may provide an alternative form for outcomes research, especially in situations in which appropriately large RCTs would unlikely be performed, it is important to remember that database analysis can only propose associations and not causation. The current format of many databases limits the type of questions that may be answered. Current Status of Outcomes Research in Regional Anesthesia Despite some convincing data on specific organ systems (coagulation, pulmonary, gastrointestinal), the overall benefits of regional anesthesia on patient-related outcomes is still controversial. Available studies are frequently beset by methodological issues, including study design and sample size, which contribute to the uncertainty of the effectiveness and efficacy of regional anesthesia on patient outcomes. Studies, for the most part, have only measured “traditional,” clinically oriented, patient-related outcomes (see Table 3).Table 3: Methodological Issues with Available Studies in Regional AnesthesiaOverview of Current Studies: Methodological Concerns There are many methodological concerns in evaluation of the efficacy and effectiveness of regional anesthesia and analgesia on (clinically oriented) patient outcomes. One major criticism of available studies is inadequate sample sizes reflecting the small incidence of outcome events, thus affecting the ability of investigators to detect clinically significant differences. For example, approximately 3000 patients would be needed to determine if an intervention (regional anesthesia) could decrease the incidence of a surrogate endpoint (myocardial ischemia) from 30% to 20% (11). Enrollment of smaller-risk subjects or those undergoing less invasive surgery would increase sample sizes even further because of the consequent smaller incidence of the outcome event studied (12–14). One of the difficulties in measuring some anesthesia-related clinical outcomes is the rarity in which these events occur (e.g., death, of the of such an it may be difficult (and as a result of the large sample to evaluate the effectiveness of an intervention on outcomes. of a surrogate a related but more frequently or measured may facilitate of outcomes with a smaller sample size and Despite some anesthesiologists have used surrogate such as and postoperative and from a trial using surrogate may be if there is a between the surrogate (e.g., ischemia) and true outcomes (e.g., however, it is rare that these are and the between surrogate and true outcomes have been with subsequent analysis of the between a surrogate endpoint and true outcome may require a trial using a large sample size to that using true outcomes Thus, surrogate may not be a of patient-related outcomes. Although most studies on the efficacy of regional versus general anesthesia on clinically patient outcomes, few trials have postoperative the study determine the of postoperative regional analgesia on patient outcomes, an postoperative regional using be for an to provide benefits as the incidence of some outcomes in the postoperative of regional analgesia An of an appropriately trial to the effect of postoperative regional analgesia on outcomes is the PIRAT study in which patients undergoing randomized to one of general anesthesia with postoperative analgesia or or anesthesia with postoperative analgesia or In general, there are few trials in this it is difficult to determine the effect of postoperative regional analgesia on outcomes. In addition, many studies not measure at and with Although regional anesthesia-analgesia provides postoperative improve clinically outcomes despite the benefits of regional analgesia with (with will potentially patients to in postoperative (e.g., which may facilitate and in outcomes Finally, even if a RCT could be with sample it may not be to results from such a protocol to typical clinical care in the and at of any conclusions from such a trial to the clinical would need to be with In general, RCTs (e.g., PIRAT and the efficacy of regional versus general anesthesia on patient outcomes of clinical care by and limits on such as and Thus, the results of regional versus general anesthesia RCTs may be difficult to as such is not to occur in the typical clinical However, this not that the results from such RCTs would be For example, detailed of the PIRAT that patients randomized to general anesthesia more interventions to study a regional anesthesia-analgesia may provide benefits in a less especially in the presence of postoperative that may include regional and a randomized trial the efficacy of regional anesthesia to that of general anesthesia on patient outcomes is a difficult at especially in the current trials may be however, with data and analysis from and the of patients in randomized trials with may prevent of these trials Current studies this issue have methodological including and thus incidence outcomes, which may affect interpretation of data and result in potentially Current Outcomes Data Although many small trials the efficacy of regional to general anesthesia on a variety of outcomes have been the benefits of regional anesthesia-analgesia are controversial. However, there have been some data that attempt to this of investigators have an overview of all randomized trials regional or general anesthesia, of the outcomes of interest. Studies and the study to data and provide unpublished One trials with subjects and on an compared with general anesthesia, regional anesthesia overall mortality by approximately 30% The use of regional anesthesia with one patients of with more than of by events, or Although there power to and limitations to meta-analysis in general (see Types of Data and Data regional anesthesia the of by by by by by by and by Thus, it that use of regional anesthesia postoperative in a wide variety of Although not discussed in there are many and benefits of regional anesthesia that may and these findings surgery general anesthesia and may be with use of regional Although the of this is include by the with and with may to and events, such as and and may contribute to more than in the United States with general anesthesia, use of regional anesthesia is with a significant decrease in events, especially and Regional anesthesia incidence of as by several randomized trials meta-analysis of randomized trials regional versus general anesthesia for of also that patients general anesthesia a increased incidence of of postoperative regional analgesia with may also contribute to a incidence of Although many of these trials have not used or have to presence of retrospective data that regional anesthesia will still provide a in the incidence of of presence or of of regional anesthesia is with a significant decrease in Randomized trials have that the use of anesthesia or in with general anesthesia the incidence of or through of In addition, a randomized trial has a incidence of in patients undergoing regional anesthesia Finally, in an analysis of randomized trials regional anesthesia the of by and by postoperative is common surgery general anesthesia and may be by several factors, including an increase from or postoperative use of for and of of regional anesthesia-analgesia of postoperative and is with an of criteria randomized trials have when compared with analgesia general anesthesia, the use of analgesia with a is with of surgery randomized trials differences between regional analgesia and analgesia in of however, the of postoperative regional analgesia may have been brief to provide significant benefits randomized trials have when compared with for postoperative the use of is with of surgery is whether the use of will provide of when compared with that with as the randomized trials the of to that of provide conflicting results There is a significant decrease in and surgery general anesthesia as a result of inadequate increase in and and of Many trials with different study and have been to determine the effect of the on a variety of outcomes. is difficult to any conclusions from as many are use surrogate and yield conflicting results. meta-analysis of RCTs the effect of postoperative on postoperative with postoperative analgesia with incidence of despite there differences in surrogate of in between with the incidence of but not the incidence of There significant differences in analgesia or between or of The use of or analgesia not with any significant in or Other and and The benefits of regional anesthesia-analgesia on outcomes with to other organ such as the and are not The surgery general anesthesia has been and may be or even by the use of regional The results in a and may affect and Despite the many potentially on various organ the association between the and patient outcomes is Thus, without this any or effect of regional anesthesia-analgesia on patient outcomes through of the be is surgery general anesthesia and may affect patient outcomes by to the development of increasing cost of care, and the possibility growth and Although the is not and of may contribute to Regional anesthesia may through the or decreasing with a subsequent decrease in the need for or product which has been with Although the effect of regional anesthesia-analgesia on patient outcomes through of is not randomized trials have a decrease in the incidence of postoperative in subjects analgesia Furthermore, analysis of data from randomized trials that regional anesthesia with a risk of or other The effect of regional versus general anesthesia on has been in several randomized trials one any of regional anesthesia on postoperative as measured by Although most trials have of regional anesthesia in the of postoperative the effect of postoperative regional analgesia on has not been carefully There are many for the development of postoperative including of postoperative regional are with analgesia when compared with regional analgesia may provide some with to postoperative events, such as and and death, occur in the postoperative Although regional anesthesia-analgesia may provide many benefits by the postoperative and a of there are conclusions the effect of regional anesthesia-analgesia on outcomes randomized trials have not any of regional anesthesia-analgesia on patient outcomes however, one study an increase in on of postoperative analgesia analysis of randomized trials that there approximately in those regional anesthesia Economic Outcomes and The effect of regional anesthesia-analgesia on economic outcomes has not been In general, economic evaluation of any intervention on outcomes is difficult at economic evaluation of the of regional anesthesia of many issues, including types of economic measurements (e.g., and analysis and the economic of any beneficial clinical outcomes by regional measurements or analysis of economic data may result in conclusions the economic of regional economic data can be because there are several types of economic analysis, including type of analysis types of costs and benefits and and and perspective for analysis payer, which may be for clinical may not be for economic as many RCTs include economic evaluation without or sample size or methods of statistical cost data are and the use of statistical methods may result in results The use of analysis, such as with to the of the and is especially useful when with (e.g., or the and may have different The of a specific incorporates the used to provide that cost with are considered or typical (e.g., and with clinical Although costs are an important of cost, this of cost is not as the cost of a also include or costs and assessment of which may include and and mortality and and economic analysis of interventions occur frequently in the economic data and evaluation of an intervention as regional anesthesia) for subsequent studies is important as clinical or health may be based on these data there has been of costs or with use of regional anesthesia and analgesia. Although costs with regional analgesia may greater than that of regional anesthesia-analgesia may provide economic benefits through such as decreasing patient and or of For example, data from a meta-analysis of randomized trials that mortality by approximately 30% in patients regional anesthesia when compared with those general anesthesia Regional anesthesia also patient by decreasing risk of development of and Other randomized trials and meta-analysis also a decrease in and Regional anesthesia-analgesia may also provide economic benefits by decreasing of through of postoperative or benefits of a regional Although postoperative is not an of of inadequate of postoperative is one of the for surgery Randomized trials that the benefits of analgesia with facilitate of criteria than those in patients undergoing Thus, regional anesthesia-analgesia may improve clinically outcomes and decrease of which in beneficial economic outcomes. Although used in other measurements have not been used to the of regional generally of validated instruments that physical, psychologic, and social variables. Data obtained from these instruments may be Although there are many validated instruments available for measuring some studies may not those which are or which may some as to the validity of results. There are several measurements may not have been prevalent in the Health care with patients on a more are generally more familiar with outcomes measurements (e.g., mortality and The of measurements to clinical situations may be difficult to as there has been research on the between clinical and measurements and the effect of clinical interventions on Finally, measurements have not been in an such as in the postoperative and have been generally used a time than one Thus, use of measurements is by of information with to and benefits in an clinical and of measurements as or The of regional anesthesia-analgesia on measurements have not be data that regional anesthesia-analgesia as of a to postoperative will facilitate of measurements assessed at and surgery is whether using validated instruments to patient in the postoperative one is The of some measurements and the possibility that the decrease in general functional status may any differences between postoperative and may the use of current validated measurements in the postoperative However, regional analgesia generally provides postoperative and of postoperative may affect measurements by with and The quality of analgesia is an important outcome and may improve and functional of Thus, several need to be addressed measurements can be in the and that time, conclusions can be on the effect of regional anesthesia-analgesia on is an important measure of outcome and has become more significant as health care use it as a measure of or as a of patient satisfaction may however, design and use of may to Many surveys of and between satisfaction with the of or with overall or care (2). patient satisfaction reflects factors, assessment a that can and instruments of true (2). studies patient satisfaction and regional anesthesia-analgesia have not used validated instruments for measuring satisfaction of regional anesthesia has been but the effect of regional anesthesia-analgesia on patient satisfaction has not been Although there are many factors that may patient satisfaction, increased of postoperative are with of patient satisfaction By postoperative regional analgesia may potentially affect patient however, it may be difficult to between satisfaction with and other aspects of care Outcomes Research in Regional Anesthesia and The future of outcomes research in regional anesthesia-analgesia in the evaluation of the effect of regional anesthesia-analgesia on economic and “nontraditional” and patient outcomes. of any potential economic or other patient-related benefits of regional anesthesia-analgesia is especially important in of decreasing for postoperative potential for research is the evaluation of the of postoperative regional analgesia to patient outcomes. Finally, of an to may facilitate the use of regional anesthetic in the for future of the effect of regional anesthesia-analgesia on patient outcomes is in 1: for the of regional anesthesia and postoperative regional analgesia on patient Despite the use of clinically measurements, are to increasing use of validated and patient satisfaction instruments to evaluate the efficacy of regional anesthesia-analgesia on patient outcomes. and clinical of measurements in the may of regional especially in the postoperative regional analgesia may improve and patient Although there are several methodological that may hinder use of these measurements in the postoperative of and patient satisfaction in clinical trials may to the efficacy of regional anesthesia-analgesia on patient outcomes. Economic of Regional Anesthesia and Although anesthesia may to of health care costs in the United States there is a of information the effect of regional anesthesia-analgesia on economic outcomes. The between the use of regional anesthesia and postoperative regional analgesia and potential beneficial economic outcomes, in through in clinically outcomes, and in of be is important that economic data and analysis be future because and may clinical or economic on these the of to The of current trials has been to potential benefits of regional anesthesia on clinically patient outcomes. Despite some data in outcomes the of postoperative regional analgesia on and patient outcomes has not been even many clinically outcomes, such as or and may in the postoperative of the in the of postoperative regional analgesia on patient-related outcomes in the that many postoperative in the (e.g., and the postoperative research is needed on the effect of postoperative regional analgesia on various outcomes including patient satisfaction, of and other clinically related outcomes. In addition, the of regional analgesia as an important of a to postoperative patient by and and to be further to to the of the available from research and to clinical and practice. The relatively in using in an attempt to provide the care for an patient has been by to research (e.g., the Despite some drawbacks may become a in clinical practice. In addition, may a significant in the development of clinical practice is that investigators to the efficacy of regional anesthesia-analgesia on various outcomes as and at the benefits of regional anesthesia-analgesia in clinical practice. Outcomes research in regional anesthesia-analgesia has traditionally focused on clinically outcomes. There is significant data to the benefits of regional anesthesia-analgesia on overall mortality and organ systems (coagulation, pulmonary, The efficacy of regional anesthesia-analgesia on outcomes, such as patient satisfaction, and assessments, is not at this more of patient-related outcomes and the of postoperative regional analgesia will provide in regional anesthesia-analgesia outcomes research as the