Vol. 220, No. 4, April 2015
62. Guignard B, Bossard AE, Coste C, et al. Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology 2000;93: 409e417. 63. Chia YY, Liu K, Wang JJ, et al. Intraoperative high dose fentanyl induces postoperative fentanyl tolerance. Can J Anaesth 1999;46:872e877. 64. Mendel HG, Guarnieri KM, Sundt LM, Torjman MC. The effects of ketorolac and fentanyl on postoperative vomiting and analgesic requirements in children undergoing strabismus surgery. Anesth Analg 1995;80:1129e1133. 65. Barletta JF, Asgeirsson T, Senagore AJ. Influence of intravenous opioid dose on postoperative ileus. Ann Pharmacother 2011;45:916e923. 66. Goettsch WG, Sukel MP, van der Peet DL, et al. In-hospital use of opioids increases rate of coded postoperative paralytic ileus. Pharmacoepidemiol Drug Saf 2007;16:668e674. 67. Guignard B, Coste C, Costes H, et al. Supplementing desflurane-remifentanil anesthesia with small-dose ketamine reduces perioperative opioid analgesic requirements. Anesth Analg 2002;95:103e108. table of contents. 68. Celerier E, Rivat C, Jun Y, et al. Long-lasting hyperalgesia induced by fentanyl in rats: preventive effect of ketamine. Anesthesiology 2000;92:465e472. 69. Hanna MN, Gonzalez-Fernandez M, Barrett AD, et al. Does patient perception of pain control affect patient satisfaction across surgical units in a tertiary teaching hospital? Am J Med Qual 2012;27:411e416. 70. Cohen ME, Bilimoria KY, Ko CY, et al. Variability in length of stay after colorectal surgery: assessment of 182 hospitals in the national surgical quality improvement program. Ann Surg 2009;250:901e907. 71. Ahmed Ali U, Dunne T, Gurland B, et al. Actual versus estimated length of stay after colorectal surgery: which factors influence a deviation? Am J Surg 2014;208:663e669. 72. Khuri SF, Henderson WG, DePalma RG, et al. Determinants of long-term survival after major surgery and the adverse effect of postoperative complications. Ann Surg 2005;242:326e341; discussion 341e343. 73. Lovely JK, Maxson PM, Jacob AK, et al. Case-matched series of enhanced versus standard recovery pathway in minimally invasive colorectal surgery. Br J Surg 2012;99:120e126. 74. Roulin D, Donadini A, Gander S, et al. Cost-effectiveness of the implementation of an enhanced recovery protocol for colorectal surgery. Br J Surg 2013;100:1108e1114. 75. Fine MJ, Pratt HM, Obrosky DS, et al. Relation between length of hospital stay and costs of care for patients with communityacquired pneumonia. Am J Med 2000;109:378e385.
Discussion DR ROBERT R CIMA (Rochester, MN): Enhanced recovery after surgery (ERAS) is really a minimalist sort of principle. As you said, it’s multidisciplinary and across time periods. I was interested to see that in your protocol, there are multiple steps that go beyond this normal ERAS principle, such as the use of continuous IV infusion for pain medicines, nonopioid, but still lidocaine and ketamine, as well as the implementation and use of alvimopan, which is controversial in this setting because it stacks the deck because it adds another
Thiele et al
Discussion
443
layer of complexity into your analysis. So are you really stacking the deck? Is this truly following the basic principles of ERAS? You provide aggregate compliance data, basically more end result data in the sense of your work on fluids and reducing the amount of fluids, reducing the morphine equivalent. Did you track compliance with the individual steps? Was there a break point at which that was important? Were all the steps important? Are there individual steps that are more important than others? Can you discuss that? As you mentioned in your last few slides, implementing change is significant. This is a cross-disciplinary change. Did you have dedicated teams initially, or do you maintain dedicated teams, or does any anesthesiologist who is assigned to your room come in and follow this? How do you track that type of thing? Similarly, in nursing care and the involvement of residents, how strictly are those rules followed? How do you sustain that? Last, you went over the lessons learned, but this is a process change. Can it be expanded throughout your institution to other projects? What would you give as important lessons learned? DR EUGENE FOLEY (Madison, WI): There is growing literature suggesting that in a variety of clinical settings, the use of multidisciplinary, standardized patient care protocols can improve quality of care, as measured by increased efficiency and decreased complications. The exact mechanism behind this phenomenon is probably multifactorial, but there is something about variation in patient care or processes of care that has been repeatedly shown to increase cost and lead to poorer outcomes. Dr Hedrick and her colleagues have effectively taken this strategy to the postoperative care of their colorectal surgery patients and demonstrated impressive reductions in length of stay and postoperative complications. I have several questions for the authors. 1. All of us who take care of gastrointestinal surgery patients recognize that some patients simply don’t tolerate early refeeding well. Do your data help us identify the characteristics of such patients? If so, should we exclude them from such a protocol? 2. You point out that several of the elements in your ERAS protocol are different than those of other ERAS protocols, which have shown similar results, such as the use of a bowel preparation and the single-shot spinal. Do you have any sense about which of the elements of your protocol are the most important: decreased narcotic use, fluid therapy, or simply the change in patient and provider expectations? 3. Finally, I can’t help but notice that the surgical site infection (SSI) rate in your protocol group was less than half that in the control group. We know that SSI rate is a major contributor to increased length of stay and cost after colorectal surgery. Did the ERAS protocol directly affect your SSI rates? If not, is it possible that some of the improvements in length of stay and cost were due to SSI reduction, not the ERAS protocol itself? DR RICHARD LYNN (Palm Beach, FL): I initially wanted to discuss this paper because I did not see in the abstract any mention of Entereg (Cubist Pharmaceuticals) or alvimopan, but obviously you put that on your list of things that you do, but really didn’t mention anything else about it. I have no disclosures about any financial interests in the drug or the company, but I must say
444
Thiele et al
Discussion
that the double-blind randomized prospective controlled study that was carried out with approximately 7,000 patients, was very convincing. Steve Wexner, at Cleveland Clinic Florida, and a Regent of the College, was one of the principal investigators. I adapted that in my hospital and had to fight the pharmacy and therapeutics committee initially for 2 years to get it on the formulary. At the end of 2 more years, they thanked me for the perceived cost savings to the hospital. In my personal experience, having used it regularly where indicated, I am convinced that it reduces the length of stay, it reduces ileus, and it reduces the time to return of bowel function. I wonder, in your list of variables, which variable is the one? I, for one, can say that, having already adopted no nasogastric (NG) tubes, etc, etc, that I am impressed that this is a very effective modality. Was there any variable looked at as to the use or nonuse of NG tubes, and its relationship to your results? DR SUSAN GALANDIUK (Louisville, KY): This paper adds to the literature regarding the efficacy of ERAS protocols. There are many variations of these. Most of these require “no” bowel preparation. I note that you have continued bowel preparation. Was there a reason for this? Also, it was interesting that goal-directed fluid management was part of your protocol. Although fluid minimization has been a part of ERAS protocols, goal-directed management with a finger plethysmography, is something specifically different. How much do you think that the reduction of fluids intraoperatively and your anesthesiologists’ change in fluid management contributed to your results? The second question regards cost savings. While there are dramatic cost savings, the effectiveness of ERAS protocols relies on nurse teaching preoperatively and having the patients “buy in” that they are going to be discharged from the hospital sooner, that they are going to need to ambulate sooner, etc. For the few of us who are still unsalaried and not employed by a hospital or clinic, who pays for those additional nurse salaries to do that education? In an era of decreasing reimbursement, I think that this is a very important point. The last question concerns the rate of readmission. With many studies, earlier hospital discharge is associated with a higher rate of hospital readmission. With your data, it is just the reverse. What were the causes of readmission in the 2 cohorts, the historical cohort as well as the ERAS cohort? DR DAN STANLEY (Chattanooga, TN): My question really has to do with patient assignment with this particular study with regard to patients who may have problems with fluid management, eg, someone with right-sided heart failure or pre-existing renal failure. What type of changes or differences in compliance were there among patients that might account for the low risk that you had for renal sufficiency in this number of patients? DR TRACI HEDRICK: For the sake of time, I’m going to try to summarize all the questions together. I will start with the questions that centered on the common theme of what exactly about the protocol led to the difference in outcomes? We are frequently asked that question. The answer is that we don’t know because we changed everything at once, but honestly, to us, it doesn’t matter
J Am Coll Surg
as long as the protocol as a whole is effective. In the beginning of the process, we sat down as a multidisciplinary group and we walked through every step of the patient care experience. We standardized all of it by looking at the most current data in the literature. For instance, we elected to use Entereg. I believe that we probably can omit the Entereg because we are hardly using any opioids. But others in our group are hesitant to do that, so we are keeping the Entereg for now. In my opinion, the most important aspects of enhanced recovery are standardization, the avoidance of opioids, fluid restriction, and setting expectations through preoperative patient education. I think each of those are vitally important and can be accomplished through various different management strategies. To get to Dr Cima’s questions about the compliance data; this really was a grassroots effort, so we could only collect so much data. We used the morphine equivalence as the surrogate for opioid consumption. About 75% of patients got the spinal. About 40% of patients couldn’t get the Celebrex (Pfizer) because of the cardiac toxicity. But, really, the key is just to reduce the amount of opioid the patients receive, and we chose to do this through the multimodal strategy that I outlined in the presentation. We did have a dedicated anesthesia team, particularly in the beginning of protocol implementation. We initially restricted it to 6 anesthesiologists, who were open-minded to the idea of enhanced recovery, and 6 Certified Registered Nurse Anesthetists. After 6 months, we opened it up to anyone and we have still had good success with it. As far as expansion, we are expanding it next to gynecologic oncology, then on to hepatobiliary. We are even working with our spine team. Virtually every service line in our hospital has expressed interest in some capacity. Our administration has now hired a nurse coordinator just for these efforts. To identify the patients who don’t do well with early postoperative feeding, we assess for the risk of aspiration in the preoperative clinic. If they have had stroke or have dysphagia, we don’t feed them right away. If they do show the earliest signs of an ileus, we’ll back off the feeding because, of course, aspiration is a very serious complication. However, as long as you’re careful and watch them closely, we have found that most patients do okay. As to Dr Foley’s question regarding whether the reduction in surgical site infection led to our improvements in outcome, it’s hard to tell. I don’t think that would account for all the differences that we experienced. As I have said before, you only have to see 1 of these patients in real time to see that there’s just something drastically different about them. I do want to look further into the surgical site infection data, but I genuinely don’t think that was the only difference. I will move on to the questions related to the bowel preparation and the fluid management with the Pleth Variability Index (PVI), which were unique aspects of our protocol. We felt that the mechanical bowel preparation with oral antibiotics (which is the key here) is very important in reducing surgical site infection. That topic could be an entire hour-long talk in and of itself. However, I think we have proven here that you can still successfully fluid restrict and do the carbohydrate loading with a bowel preparation. The constant evaluation of fluid status with PVI during the case
Vol. 220, No. 4, April 2015
provided useful information to the anesthesia team. It was able to demonstrate that, despite the bowel preparation, the majority of patients were not dehydrated. All of our elective patients went on this protocol despite their comorbidities, including end-stage renal disease patients and patients with significant heart disease. I will make just 1 final point about the preoperative education in our clinic. In our experience, the preoperative teaching is about a
Thiele et al
Discussion
445
7-minute talk from our clinical coordinator. We made a patient booklet in a Word document that included in-depth information about what to expect before, during, and after surgery. We printed it out ourselves in our office and put it in a binder. You can really do this entire process on a shoestring budget. We have now made a video, but regardless, it doesn’t take that much time and it is well worth the small investment.
62. Guignard B, Bossard AE, Coste C, et al. Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology 2000;93: 409e417. 63. Chia YY, Liu K, Wang JJ, et al. Intraoperative high dose fentanyl induces postoperative fentanyl tolerance. Can J Anaesth 1999;46:872e877. 64. Mendel HG, Guarnieri KM, Sundt LM, Torjman MC. The effects of ketorolac and fentanyl on postoperative vomiting and analgesic requirements in children undergoing strabismus surgery. Anesth Analg 1995;80:1129e1133. 65. Barletta JF, Asgeirsson T, Senagore AJ. Influence of intravenous opioid dose on postoperative ileus. Ann Pharmacother 2011;45:916e923. 66. Goettsch WG, Sukel MP, van der Peet DL, et al. In-hospital use of opioids increases rate of coded postoperative paralytic ileus. Pharmacoepidemiol Drug Saf 2007;16:668e674. 67. Guignard B, Coste C, Costes H, et al. Supplementing desflurane-remifentanil anesthesia with small-dose ketamine reduces perioperative opioid analgesic requirements. Anesth Analg 2002;95:103e108. table of contents. 68. Celerier E, Rivat C, Jun Y, et al. Long-lasting hyperalgesia induced by fentanyl in rats: preventive effect of ketamine. Anesthesiology 2000;92:465e472. 69. Hanna MN, Gonzalez-Fernandez M, Barrett AD, et al. Does patient perception of pain control affect patient satisfaction across surgical units in a tertiary teaching hospital? Am J Med Qual 2012;27:411e416. 70. Cohen ME, Bilimoria KY, Ko CY, et al. Variability in length of stay after colorectal surgery: assessment of 182 hospitals in the national surgical quality improvement program. Ann Surg 2009;250:901e907. 71. Ahmed Ali U, Dunne T, Gurland B, et al. Actual versus estimated length of stay after colorectal surgery: which factors influence a deviation? Am J Surg 2014;208:663e669. 72. Khuri SF, Henderson WG, DePalma RG, et al. Determinants of long-term survival after major surgery and the adverse effect of postoperative complications. Ann Surg 2005;242:326e341; discussion 341e343. 73. Lovely JK, Maxson PM, Jacob AK, et al. Case-matched series of enhanced versus standard recovery pathway in minimally invasive colorectal surgery. Br J Surg 2012;99:120e126. 74. Roulin D, Donadini A, Gander S, et al. Cost-effectiveness of the implementation of an enhanced recovery protocol for colorectal surgery. Br J Surg 2013;100:1108e1114. 75. Fine MJ, Pratt HM, Obrosky DS, et al. Relation between length of hospital stay and costs of care for patients with communityacquired pneumonia. Am J Med 2000;109:378e385.
Discussion DR ROBERT R CIMA (Rochester, MN): Enhanced recovery after surgery (ERAS) is really a minimalist sort of principle. As you said, it’s multidisciplinary and across time periods. I was interested to see that in your protocol, there are multiple steps that go beyond this normal ERAS principle, such as the use of continuous IV infusion for pain medicines, nonopioid, but still lidocaine and ketamine, as well as the implementation and use of alvimopan, which is controversial in this setting because it stacks the deck because it adds another
Thiele et al
Discussion
443
layer of complexity into your analysis. So are you really stacking the deck? Is this truly following the basic principles of ERAS? You provide aggregate compliance data, basically more end result data in the sense of your work on fluids and reducing the amount of fluids, reducing the morphine equivalent. Did you track compliance with the individual steps? Was there a break point at which that was important? Were all the steps important? Are there individual steps that are more important than others? Can you discuss that? As you mentioned in your last few slides, implementing change is significant. This is a cross-disciplinary change. Did you have dedicated teams initially, or do you maintain dedicated teams, or does any anesthesiologist who is assigned to your room come in and follow this? How do you track that type of thing? Similarly, in nursing care and the involvement of residents, how strictly are those rules followed? How do you sustain that? Last, you went over the lessons learned, but this is a process change. Can it be expanded throughout your institution to other projects? What would you give as important lessons learned? DR EUGENE FOLEY (Madison, WI): There is growing literature suggesting that in a variety of clinical settings, the use of multidisciplinary, standardized patient care protocols can improve quality of care, as measured by increased efficiency and decreased complications. The exact mechanism behind this phenomenon is probably multifactorial, but there is something about variation in patient care or processes of care that has been repeatedly shown to increase cost and lead to poorer outcomes. Dr Hedrick and her colleagues have effectively taken this strategy to the postoperative care of their colorectal surgery patients and demonstrated impressive reductions in length of stay and postoperative complications. I have several questions for the authors. 1. All of us who take care of gastrointestinal surgery patients recognize that some patients simply don’t tolerate early refeeding well. Do your data help us identify the characteristics of such patients? If so, should we exclude them from such a protocol? 2. You point out that several of the elements in your ERAS protocol are different than those of other ERAS protocols, which have shown similar results, such as the use of a bowel preparation and the single-shot spinal. Do you have any sense about which of the elements of your protocol are the most important: decreased narcotic use, fluid therapy, or simply the change in patient and provider expectations? 3. Finally, I can’t help but notice that the surgical site infection (SSI) rate in your protocol group was less than half that in the control group. We know that SSI rate is a major contributor to increased length of stay and cost after colorectal surgery. Did the ERAS protocol directly affect your SSI rates? If not, is it possible that some of the improvements in length of stay and cost were due to SSI reduction, not the ERAS protocol itself? DR RICHARD LYNN (Palm Beach, FL): I initially wanted to discuss this paper because I did not see in the abstract any mention of Entereg (Cubist Pharmaceuticals) or alvimopan, but obviously you put that on your list of things that you do, but really didn’t mention anything else about it. I have no disclosures about any financial interests in the drug or the company, but I must say
444
Thiele et al
Discussion
that the double-blind randomized prospective controlled study that was carried out with approximately 7,000 patients, was very convincing. Steve Wexner, at Cleveland Clinic Florida, and a Regent of the College, was one of the principal investigators. I adapted that in my hospital and had to fight the pharmacy and therapeutics committee initially for 2 years to get it on the formulary. At the end of 2 more years, they thanked me for the perceived cost savings to the hospital. In my personal experience, having used it regularly where indicated, I am convinced that it reduces the length of stay, it reduces ileus, and it reduces the time to return of bowel function. I wonder, in your list of variables, which variable is the one? I, for one, can say that, having already adopted no nasogastric (NG) tubes, etc, etc, that I am impressed that this is a very effective modality. Was there any variable looked at as to the use or nonuse of NG tubes, and its relationship to your results? DR SUSAN GALANDIUK (Louisville, KY): This paper adds to the literature regarding the efficacy of ERAS protocols. There are many variations of these. Most of these require “no” bowel preparation. I note that you have continued bowel preparation. Was there a reason for this? Also, it was interesting that goal-directed fluid management was part of your protocol. Although fluid minimization has been a part of ERAS protocols, goal-directed management with a finger plethysmography, is something specifically different. How much do you think that the reduction of fluids intraoperatively and your anesthesiologists’ change in fluid management contributed to your results? The second question regards cost savings. While there are dramatic cost savings, the effectiveness of ERAS protocols relies on nurse teaching preoperatively and having the patients “buy in” that they are going to be discharged from the hospital sooner, that they are going to need to ambulate sooner, etc. For the few of us who are still unsalaried and not employed by a hospital or clinic, who pays for those additional nurse salaries to do that education? In an era of decreasing reimbursement, I think that this is a very important point. The last question concerns the rate of readmission. With many studies, earlier hospital discharge is associated with a higher rate of hospital readmission. With your data, it is just the reverse. What were the causes of readmission in the 2 cohorts, the historical cohort as well as the ERAS cohort? DR DAN STANLEY (Chattanooga, TN): My question really has to do with patient assignment with this particular study with regard to patients who may have problems with fluid management, eg, someone with right-sided heart failure or pre-existing renal failure. What type of changes or differences in compliance were there among patients that might account for the low risk that you had for renal sufficiency in this number of patients? DR TRACI HEDRICK: For the sake of time, I’m going to try to summarize all the questions together. I will start with the questions that centered on the common theme of what exactly about the protocol led to the difference in outcomes? We are frequently asked that question. The answer is that we don’t know because we changed everything at once, but honestly, to us, it doesn’t matter
J Am Coll Surg
as long as the protocol as a whole is effective. In the beginning of the process, we sat down as a multidisciplinary group and we walked through every step of the patient care experience. We standardized all of it by looking at the most current data in the literature. For instance, we elected to use Entereg. I believe that we probably can omit the Entereg because we are hardly using any opioids. But others in our group are hesitant to do that, so we are keeping the Entereg for now. In my opinion, the most important aspects of enhanced recovery are standardization, the avoidance of opioids, fluid restriction, and setting expectations through preoperative patient education. I think each of those are vitally important and can be accomplished through various different management strategies. To get to Dr Cima’s questions about the compliance data; this really was a grassroots effort, so we could only collect so much data. We used the morphine equivalence as the surrogate for opioid consumption. About 75% of patients got the spinal. About 40% of patients couldn’t get the Celebrex (Pfizer) because of the cardiac toxicity. But, really, the key is just to reduce the amount of opioid the patients receive, and we chose to do this through the multimodal strategy that I outlined in the presentation. We did have a dedicated anesthesia team, particularly in the beginning of protocol implementation. We initially restricted it to 6 anesthesiologists, who were open-minded to the idea of enhanced recovery, and 6 Certified Registered Nurse Anesthetists. After 6 months, we opened it up to anyone and we have still had good success with it. As far as expansion, we are expanding it next to gynecologic oncology, then on to hepatobiliary. We are even working with our spine team. Virtually every service line in our hospital has expressed interest in some capacity. Our administration has now hired a nurse coordinator just for these efforts. To identify the patients who don’t do well with early postoperative feeding, we assess for the risk of aspiration in the preoperative clinic. If they have had stroke or have dysphagia, we don’t feed them right away. If they do show the earliest signs of an ileus, we’ll back off the feeding because, of course, aspiration is a very serious complication. However, as long as you’re careful and watch them closely, we have found that most patients do okay. As to Dr Foley’s question regarding whether the reduction in surgical site infection led to our improvements in outcome, it’s hard to tell. I don’t think that would account for all the differences that we experienced. As I have said before, you only have to see 1 of these patients in real time to see that there’s just something drastically different about them. I do want to look further into the surgical site infection data, but I genuinely don’t think that was the only difference. I will move on to the questions related to the bowel preparation and the fluid management with the Pleth Variability Index (PVI), which were unique aspects of our protocol. We felt that the mechanical bowel preparation with oral antibiotics (which is the key here) is very important in reducing surgical site infection. That topic could be an entire hour-long talk in and of itself. However, I think we have proven here that you can still successfully fluid restrict and do the carbohydrate loading with a bowel preparation. The constant evaluation of fluid status with PVI during the case
Vol. 220, No. 4, April 2015
provided useful information to the anesthesia team. It was able to demonstrate that, despite the bowel preparation, the majority of patients were not dehydrated. All of our elective patients went on this protocol despite their comorbidities, including end-stage renal disease patients and patients with significant heart disease. I will make just 1 final point about the preoperative education in our clinic. In our experience, the preoperative teaching is about a
Thiele et al
Discussion
445
7-minute talk from our clinical coordinator. We made a patient booklet in a Word document that included in-depth information about what to expect before, during, and after surgery. We printed it out ourselves in our office and put it in a binder. You can really do this entire process on a shoestring budget. We have now made a video, but regardless, it doesn’t take that much time and it is well worth the small investment.
