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Enhanced recovery after cardiac surgery protocol reduces perioperative opioid use

Open AccessPublished:September 05, 2022DOI:https://doi.org/10.1016/j.xjon.2022.08.008

      Abstract

      Objective

      Enhanced Recovery After Surgery protocols are relatively new in cardiac surgery. Enhanced Recovery After Surgery addresses perioperative analgesia by implementing multimodal pain control regimens that include both opioid and nonopioid components. We investigated the effects of an Enhanced Recovery After Surgery protocol at our institution on postoperative outcomes with particular focus on analgesia.

      Methods

      Single-center retrospective study comparing perioperative opioid use before and after implementation of an Enhanced Recovery After Surgery protocol at our institution. Subjects were divided into 2 cohorts: Enhanced Recovery After Surgery (study group from year 2020) and pre–Enhanced Recovery After Surgery (control group from year 2018). Baseline and perioperative variables including total opioid use from the day of surgery to postoperative day 5 were collected. Opioid use was calculated as morphine milligram equivalents and compared between the 2 cohorts.

      Results

      A total of 466 patients were included: 250 in the Enhanced Recovery After Surgery group and 216 in the pre–Enhanced Recovery After Surgery group. Both groups had similar baseline characteristics, but the Enhanced Recovery After Surgery group had significantly more subjects with intravenous drug use history (P < .0001), endocarditis (P < .0001), and liver disease (P = .007) compared with the pre–Enhanced Recovery After Surgery group. Every day from the day of surgery to postoperative day 5, the Enhanced Recovery After Surgery group had significant reduction (57%) in opioid use compared with the pre–Enhanced Recovery After Surgery group. Total opioid use for the entire length of stay was 259 morphine milligram equivalents in the Enhanced Recovery After Surgery group versus 452 morphine milligram equivalents in the pre–Enhanced Recovery After Surgery group (P < .0001). Subgroup analysis of subjects with intravenous drug use history did not demonstrate a significant reduction in opioid use.

      Conclusions

      Enhanced Recovery After Surgery protocols with an emphasis on multimodal pain management throughout perioperative care are associated with a significant reduction in the postoperative use of opioid analgesics.

      Graphical abstract

      Key Words

      Abbreviations and Acronyms:

      ERAS (Enhanced Recovery After Surgery), IVDU (intravenous drug use), MME (morphine milligram equivalent), NIVDU (nonintravenous drug use), NSAID (nonsteroidal anti-inflammatory drug)
      Figure thumbnail fx2
      Reduction in opioid use by postoperative day in cardiac surgery patients.
      ERAS protocols with an emphasis on multimodal analgesia are associated with significantly reduced perioperative opioid use in cardiac surgery patients.
      Standardized ERAS protocols can help optimize postoperative outcomes, particularly with respect to perioperative analgesia. A multimodal analgesic regimen consisting of both opioid and nonopioid approaches used throughout all phases of care is associated with significantly reduced perioperative opioid analgesic use in cardiac surgery patients.
      See Commentary on page 297.
      Enhanced Recovery after Surgery (ERAS) is a multimodal, multidisciplinary perioperative management strategy with the goal of optimizing patient recovery and outcomes.
      • Ljungqvist O.
      • Scott M.
      • Fearon K.C.
      Enhanced recovery after surgery: a review.
      The first ERAS protocol was developed in 2001 to standardize outcomes in colorectal surgery and was largely built on the principles established by Henrik Kehlet in the 1990s surrounding “fast-track surgery.”
      • Brown J.K.
      • Singh K.
      • Dumitru R.
      • Chan E.
      • Kim M.P.
      The benefits of enhanced recovery after surgery programs and their application in cardiothoracic surgery.
      One major aspect of ERAS addresses postoperative analgesia by implementing multimodal pain control regimens. The use of multimodal pain management protocols has been associated with reduction in opioid analgesic use, patient discomfort, and hospital length of stay across multiple surgical subspecialties.
      • Engelman D.T.
      • Ben Ali W.
      • Williams J.B.
      • Perrault L.P.
      • Reddy V.S.
      • Arora R.C.
      • et al.
      Guidelines for perioperative care in cardiac surgery: enhanced recovery after surgery society recommendations.
      ,
      • Barr L.F.
      • Boss M.J.
      • Mazzeffi M.A.
      • Taylor B.S.
      • Salenger R.
      Postoperative multimodal analgesia in cardiac surgery.
      ERAS protocols remain a relatively new paradigm in cardiac surgery where patients face unique challenges, including multiple incision sites, chest tube drainage, and invasive lines and catheters, which all contribute to patient discomfort.
      • Barr L.F.
      • Boss M.J.
      • Mazzeffi M.A.
      • Taylor B.S.
      • Salenger R.
      Postoperative multimodal analgesia in cardiac surgery.
      The goal of this study was to investigate the effects of a novel ERAS protocol at our institution on postoperative outcomes. Although we intend to report other outcomes of our protocol, this review focuses on perioperative opioid analgesic use (Figure 1).
      Figure thumbnail gr1
      Figure 1ERAS reduces postoperative opioid use. ERAS, Enhanced Recovery After Surgery; POD, postoperative day.

      Methods and Materials

      Enhanced Recovery After Surgery Protocol Development

      Our institution convened a multidisciplinary group of individuals to develop an ERAS protocol. Every discipline that interacted with cardiac surgical patients was included, with each discipline having an “ERAS Champion” to serve as a liaison to other providers within their respective fields. Our protocol was based on the Guidelines for Perioperative Care in Cardiac Surgery Enhanced Recovery After Surgery Society Recommendations and was tailored with consideration of institutional resources, feasibility of successful implementation, and the needs of our patient population.
      • Engelman D.T.
      • Ben Ali W.
      • Williams J.B.
      • Perrault L.P.
      • Reddy V.S.
      • Arora R.C.
      • et al.
      Guidelines for perioperative care in cardiac surgery: enhanced recovery after surgery society recommendations.
      After multiple iterations of the protocol, final approval was granted by unanimous agreement by the multidisciplinary champions. ERAS was implemented on all patients who underwent nonemergency cardiac surgery via median sternotomy starting in January 2020. Data variables were collected prospectively into an ERAS database, and an ERAS Leadership Team met regularly to monitor for adverse effects and logistic hurdles. This also allowed the team to identify and address challenges as they arose.

      Enhanced Recovery After Surgery Protocol Components

      The ERAS protocol addressed all phases of care: preoperative, intraoperative, and postoperative. Key components of the protocol included multimodal pain management, patient education, high protein nutritional supplementation, goal-directed intraoperative fluid and hemodynamic management, early postoperative mobilization and chest tube removal, and delirium screening (Figure 2). Although the entire ERAS protocol encompassed all of these areas, for the purposes of this manuscript we focus on the analgesic aspect of the protocol. The multimodal analgesic components included preoperative acetaminophen and gabapentin, intraoperative topical anesthetic with liposomal bupivacaine and encouragement of reduced intravenous (IV) opioid use, and postoperative opioids in combination with nonopioids such as gabapentin, nonsteroidal anti-inflammatory drugs (NSAIDs), and lidocaine patches (Table 1).
      Table 1Perioperative multimodal pain regimen
      Preoperative
       Acetaminophen 1 g 2 h before surgery
       Gabapentin 300 mg 2 h before surgery
      Intraoperative
       Recommend reduced opioid use to < 500 μg fentanyl
       Local anesthetic with liposomal bupivacaine

      10 mL chest tube sites

      15 mL incision
      Postoperative
       Dexmedetomidine (initiated in OR, continued until extubation)
       Acetaminophen 650 mg scheduled every 6 h
       Lidocaine 5% transdermal patch, applied to bilateral back or chest
       Gabapentin 100 mg TID

      100 mg BID if renal impairment
       Tramadol 50-100 mg PO every 6 h-PRN for mild pain (every 12 h for CrCl <30, max 200 mg/d)
       Oxycodone 5-10 mg PO every 4 h-PRN moderate pain
       IV opioids (eg, hydromorphone, fentanyl), PRN severe/breakthrough pain

      Dose and drug at provider discretion

      Discontinued when chest tubes removed
      OR, Operating room; TID, ter in die (3 times daily); BID, bis in die (2 times daily); PO, per os (by mouth); PRN, pro re nata (as needed); CrCl, creatinine clearance; IV, intravenous.
      Of note, opioid analgesics were not intentionally withheld or limited in the postoperative period; various narcotics were ordered for all patients and administered when requested by patients or deemed necessary to achieve adequate analgesia by nursing or physician staff. Furthermore, clinical staff were instructed that the goal was not to specifically reduce opioid use but rather that the intent with ERAS analgesia was to achieve adequate pain control to allow for enhanced overall patient recovery. Patients were also administered a 3-question survey (all using Likert scale grading) on the day of discharge, with one of the questions focused on the patient's perception of their perioperative analgesia: “How satisfied are you with how your pain was controlled in the hospital after surgery?” The 5-point Likert scale response options were “very dissatisfied,” “dissatisfied,” “neutral,” “satisfied,” or “very satisfied.”

      Study Design

      The Institutional Review Board of Indiana University approved this retrospective study on 9/25/2020 (IRB #2009811102). Informed written consent was obtained by all patients who were included in this study. Our ERAS prospective database was used to identify the study group, which included all patients who received the ERAS protocol from January to September 2020. An institutional Society of Thoracic Surgeons database was queried to identify the control group: All patients who underwent nonemergency cardiac surgery via median sternotomy from January to September 2018. This time period was chosen as the control group because the surgical attending staff were mostly unchanged (one surgeon from 2018 had departed the group and thus not included in the 2020 study group), and no ERAS components were applied in 2018. Demographic and relevant clinical data were extracted from these registries and from individual medical records. Medication administration records were reviewed, and all sources of opioid analgesic were converted into morphine milligram equivalents (MMEs) using a standardized conversion chart (Table E1).
      Centers for Disease Control and Prevention
      Calculating total daily dose of opioid for safer dosage [Internet].

      Statistical Analysis

      Patient characteristics were evaluated using frequency and proportion for all categorical variables. All continuous variables were tested for normality using Shapiro–Wilk tests and due to evidence of skewness we used median and inter quartile range for all continuous variables. We also examined the statistical difference in the patient characteristics between the control and ERAS cohorts using chi-square or Fisher exact tests and Wilcoxon rank-sum tests, as appropriate. Bivariate analyses using quantile (median) regressions were done to analyze the relationship between opioid analgesic use by postoperative days in all patients, and this analysis was repeated for 2 subgroup analyses (illicit drug use vs nonillicit drug use). Multivariable quantile regression using 50th percentile (median) of MME was performed at each cross-section of the follow-up time (postoperative day 0 to 5). To account for the panel nature of the study where multiple observations are nested within a study participant, we used multivariable quantile regression with bootstrapped clustered standard error to account for the within subject correlation. Marginal plot of linear prediction of MME over days was also created as a postestimation for the nested study design. The result was consistent with the multivariable quantile regression of MME at each cross-section of the follow-up time. All analyses were done using Stata/MP 16.1.
      StataCorp
      Stata Statistical Software: Release 16.

      Results

      In total, 466 patients were included and divided into 2 groups: n = 250 in ERAS (study group) and n = 216 in pre-ERAS (control group). Baseline characteristics of the 2 cohorts are listed in Table 2: The 2 groups were similar with the exception that the ERAS group had significantly more patients with endocarditis (n = 60 [24%] vs n = 12 [5.6%], P < .0001), a history of intravenous drug use (IVDU) (n = 56 [22%] vs n = 17 [7.9%], P < .0001), and liver disease (n = 27 [10.8%] vs n = 9 [4.2%], P < .007). These differences between the pre-ERAS and ERAS groups were partially due to the opioid epidemic and were controlled by multivariate analysis (Table E2).
      • Kadri A.N.
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      Geographic trends, patient characteristics, and outcomes of infective endocarditis associated with drug abuse in the United States from 2002 to 2016.
      Patient compliance was greatest in the postoperative period (Table E3).
      Table 2Patient characteristics
      Characteristic, n (%)Control (n = 216)ERAS (n = 250)Total (n = 466)P value
      Procedure type<.0001
       Ascending aortic47 (21.7)36 (14.4)83 (17.8)
       CABG75 (34.7)95 (38)170 (36.5)
       Valve65 (30.1)54 (21.6)119 (25.5)
       Valve + CABG12 (5.6)12 (4.8)24 (5.2)
       Other17 (7.9)53 (21.2)70 (15.0)
      Age, median (Q1, Q3)64 (57, 70)62 (51, 70)63 (55, 70).132
      Gender.542
       Male150 (69.4)167 (66.8)317 (68.0)
       Female66 (30.6)83 (33.2)149 (32.0)
      Race.568
       White188 (87.0)213 (85.2)401 (86.1)
       Non-White28 (13.0)37 (14.8)65 (14.0)
      Risk factors
       BMI, median (Q1, Q3)30 (25.9, 34.0)29 (25.0, 33.8)29 (25.4, 34.0).240
       Diabetes81 (37.5)93 (37.2)174 (37.3).947
       Endocarditis12 (5.6)60 (24)72 (15.5)<.0001
       Cerebrovascular disease31 (14.4)52 (20.8)83 (17.8).070
       Chronic lung disease55 (25.5)62 (24.8)117 (25.1).869
       Family history of CAD9 (4.2)3 (1.2)12 (2.6).074
       Hypertension180 (83.3)177 (70.8)357 (76.6).001
       Intravenous drug use17 (7.9)56 (22.4)73 (15.7)<.0001
       Last HbA1c, median (Q1, Q3)6 (5.4, 6.6)6 (5.6, 7.1)6 (5.5, 6.9).386
       Liver disease9 (4.2)27 (10.8)36 (7.7).007
       Peripheral artery disease25 (11.6)38 (15.2)63 (13.5).254
      Previous cardiac interventions
       Any78 (36.1)95 (38.0)173 (37.1).674
       CABG4 (1.9)3 (1.2)7 (1.5).709
       Valve20 (9.3)30 (12.0)50 (10.7).340
       Other cardiac surgery29 (13.4)35 (14.0)64 (13.7).858
       PCI42 (19.4)52 (20.8)94 (20.2).716
      Preoperative cardiac status
       Prior MI34 (15.7)56 (22.4)90 (19.3).120
       Heart failure66 (30.6)68 (27.2)134 (28.8).425
       Cardiogenic shock1 (0.5)2 (0.8)3 (0.6).348
       Cardiac arrhythmia48 (22.2)53 (21.2)101 (21.7).789
      Operative
       CPB use205 (94.9)244 (97.6)449 (96.4).122
       CPB time (min), median (Q1, Q3)150 (118.5, 190.5)116.5 (89, 167)135 (103, 180)<.0001
       Crossclamp time (min), median (Q1, Q3)108.5 (82, 147)86.5 (63, 123.5)94.5 (71, 133)<.0001
       Postprocedure EF204 (94.4)237 (94.8)441 (94.6).865
      ERAS, Enhanced Recovery After Surgery; CABG, coronary artery bypass grafting; BMI, Body mass index; CAD, coronary artery disease; HbA1c, hemoglobin A1c; PCI, percutaneous coronary intervention; MI, myocardial infarction; CPB, cardiopulmonary bypass; EF, ejection fraction.
      Perioperative daily opioid analgesic use was significantly reduced in the ERAS group. In the first 24 hours of care, which included the intraoperative phase of case, median opioid use was 113 MME in ERAS versus 259 MME in pre-ERAS (P < .0001). Over the ensuing 5 postoperative days, median MME in the ERAS versus pre-ERAS groups, respectively, were 48 versus 63 MME (P = .002), 30 versus 40 MME (P = .007), 20 versus 30 MME (P = .004), 15 versus 30 MME (P < .0001), and 10 versus 30 MME (P < .0001). In the multivariable quantile (median) regression, we found a similar pattern of MME by postoperative day (Figure E1, Tables E2 and E4). During the entire hospital length of stay, ERAS patients had a 57% reduction in total opioid use (459 vs 261 MME, P < .0001) (Figure 3).
      Figure thumbnail gr3
      Figure 3Pre-ERAS versus ERAS opioid analgesic use among all patients by postoperative day. ERAS, Enhanced Recovery After Surgery; POD, postoperative day.
      Because a significant portion of the ERAS group (n = 56, 22%) had a history of IVDU, a subgroup analysis was performed to see if this group also benefited from the multimodal pain management protocol. In general, the patients with a history of IVDU were younger (44 vs 64 years, P < .0001), with less comorbidities aside from endocarditis (n = 40 [54.8%] vs n = 32 [8.1%], P < .0001) and liver disease (n = 28 [38.4%] vs n = 8 [2.0%]) when compared with nonintravenous drug use (NIVDU) (Table E5). For patients with a history of IVDU, those who received the ERAS protocol had a significant reduction in opioid analgesic use on day of surgery (postoperative day zero) compared with pre-ERAS patients (318 MME vs 148 MME, P < .001), but there was no difference in the subsequent postoperative days (Figure 4). In contrast, in patients without IVDU history, ERAS patients demonstrated significant reduction in opioid analgesic use compared with pre-ERAS patients throughout the entire length of stay starting with day of surgery to postoperative day 5, respectively: 247 versus 106 MME, 62 versus 40 MME, 40 versus 25 MME, 30 versus 15 MME, 25 versus 10 MME, and 30 versus 5 MME (all days P < .0001) (Figure 5).
      Figure thumbnail gr4
      Figure 4Pre-ERAS versus ERAS opioid analgesic use among IVDU by postoperative day. ERAS, Enhanced Recovery After Surgery; IVDU, intravenous drug use; POD, postoperative day.
      Figure thumbnail gr5
      Figure 5Pre-ERAS versus ERAS opioid analgesic use among NIVDU by postoperative day. ERAS, Enhanced Recovery After Surgery; NIVDU, nonintravenous drug use; POD, postoperative day.

      Other Secondary Outcomes

      In addition to reduction in postoperative opioid use, we found that the ERAS group had chest tubes removed earlier (postoperative day 3 vs 4; P < .0001) than the pre-ERAS group. There was no significant difference in the following secondary outcomes between pre-ERAS and ERAS groups, respectively: total hospital length of stay (6 vs 6.5 days, P = .505), total intensive care unit length of stay (3.3 vs 3.1 days, P = .302), initial ventilation duration (4.7 vs 4.9 hours, P = .540), 30-day mortality (n = 5 [2.3%] vs n = 8 [3.2%], P = .779), and 30-day readmission (n = 17 [7.9%] vs n = 32 [12.8%], P = .084). Additionally, there was no difference in postoperative complications, including surgical site infection (n = 1 [0.5%] vs n = 4 [1.6%], P = .379), pneumonia (n = 14 [6.5%] vs n = 12 [4.8], P = .430), renal failure (n = 6 [2.8%] vs n = 8 [3.2%], P = .790), atrial fibrillation (n = 62, [28.7%] vs n = 69 [27.6%], P = .792), gastrointestinal side effects (n = 10 [4.6%] vs n = 13 [5.2%], P = .777), and stroke (n = 1 [0.5%] vs n = 2 [0.8%], P > .999).

      Patient Satisfaction

      In response to the predischarge survey, 79% of patients stated that they were “satisfied” or “very satisfied” with their pain control after surgery; 2.5% of patients reported being “dissatisfied” with their level of postoperative pain control.

      Discussion

      This study represents the effects after the implementation of a novel ERAS protocol and its impact on perioperative analgesic use in cardiac surgery patients at our institution.
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      Our objective in developing an ERAS protocol was to create a perioperative management strategy that would optimize patient recovery. Although analgesia is but one component of the ERAS program, we elected to focus on this aspect for purposes of this study because of its immediate and notable impact on the care pathway.
      Overall, the ERAS group had a 57% reduction in total opioid requirements during admission when compared with the control group. The primary intent of ERAS was not opioid use reduction per se; rather, the goal was to provide the patient sufficient analgesia that, in turn, could facilitate other aspects of their postoperative recovery such as early mobility and reduction of gastrointestinal and medication adverse effects. Reduction in opioid use has been proposed to enhance patient recovery my minimizing side effects including nausea, constipation, urinary retention, respiratory depression, pruritis, and delirium.
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      Our results demonstrate that the ERAS analgesic protocol successfully achieves this while also reducing opioid consumption.
      The preoperative administration of acetaminophen and gabapentinoids (gabapentin, pregabalin) is common among ERAS protocols. Administering acetaminophen before surgery has been associated with reduced pain scores and opioid analgesic use in the immediate postoperative period in noncardiac surgical patients.
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      By combining all of these different analgesic modalities, an ERAS protocol aims to combat surgical pain even before the patient arouses from general anesthesia. We also suspect that this regimen contributes to the large reduction in opioid use seen on day of surgery (postoperative day zero). This time period includes the intraoperative phase as well as the first few immediate postoperative hours, during which the patient is often still under effects of general anesthetic. Our protocol also included encouragement of reduced intraoperative reduction of opioid anesthetics and increased use of agents such as dexmedetomidine at the conclusion of surgery rather than agents such as fentanyl infusion.
      Over the subsequent 5 postoperative days, the ERAS group consistently used less opioid analgesic than the control group. This continued reduction is likely due to the postoperative multimodal regimen, which included scheduled acetaminophen, gabapentin, lidocaine topical patches, and ketorolac (in patients without contraindication) in addition to as needed tramadol, oxycodone, and hydromorphone. This regimen allowed opioid analgesics to serve as a rescue medication rather than the primary pain regimen.
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      The benefits of enhanced recovery after surgery programs and their application in cardiothoracic surgery.
      The postoperative administration of scheduled acetaminophen is ubiquitous in ERAS protocols and has been associated with a 20% to 30% decrease in morphine consumption.
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      Optimizing pain management to facilitate enhanced recovery after surgery pathways.
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      Furthermore, tramadol has a favorable safety profile in comparison with other opioid analgesics because it causes less cardiovascular and respiratory depression, is less addictive, and has a lower rate of constipation.
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      • McConnell G.
      • Woltz P.
      • Bradford W.T.
      • Ledford J.E.
      • Williams J.B.
      Enhanced recovery after cardiac surgery program to improve patient outcomes.
      ,
      • Batchelor T.J.P.
      • Rasburn N.J.
      • Abdelnour-Berchtold E.
      • Brunelli A.
      • Cerfolio R.J.
      • Gonzalez M.
      • et al.
      Guidelines for enhanced recovery after lung surgery: recommendations of the enhanced recovery after surgery (ERAS®) Society and the European Society of Thoracic Surgeons (ESTS).
      ,
      • Gregory A.J.
      • Grant M.C.
      • Manning M.W.
      • Cheung A.T.
      • Ender J.
      • Sander M.
      • et al.
      Enhanced recovery after cardiac surgery (ERAS cardiac) recommendations: an important first step-but there is much work to be done.
      In our series, ERAS patients were administered ketorolac followed by ibuprofen starting postoperative day 1. These medications could be withheld at the discretion of the surgeon for renal insufficiency or concerns of platelet dysfunction. In our study, there was no increase in acute kidney injury rates or bleeding seen in those receiving these agents.
      Williams and colleagues
      • Williams J.B.
      • McConnell G.
      • Allender J.E.
      • Woltz P.
      • Kane K.
      • Smith P.K.
      • et al.
      One-year results from the first US-based enhanced recovery after cardiac surgery (ERAS cardiac) program.
      conducted a retrospective cohort review on the implementation of ERAS protocol in cardiac surgery patients. Their postoperative protocol included scheduled acetaminophen and gabapentin. Oxycodone and fentanyl were provided as needed for pain. The ERAS group had a 30% reduction in IV opioid analgesic use on postoperative day zero. Likewise, in a prospective, observational study of cardiac surgery patients, Fleming and colleagues
      • Fleming I.O.
      • Garratt C.
      • Guha R.
      • Desai J.
      • Chaubey S.
      • Wang Y.
      • et al.
      Aggregation of marginal gains in cardiac surgery: feasibility of a perioperative care bundle for enhanced recovery in cardiac surgical patients.
      used a multimodal pain regimen which included the preoperative administration of gabapentin along with postoperative administration of acetaminophen, codeine, and as needed morphine. They demonstrated significantly lower pain scores on postoperative days 1 to 3 in the ERAS group and shorter duration of IV opioid infusion. Our results are similar to these other studies and demonstrate that multimodal pain management is associated with improved pain control and consequently reduces opioid analgesic use after cardiac surgery. It is important to note that our results were not achieved by sacrificing patient perception of pain control. In fact, approximately 80% of our ERAS patients reported being satisfied or very satisfied with their analgesic regimen. Because of the retrospective nature of this study, we were unable to ascertain patient perceptions of the control group. Nonetheless, our results indicate that the pain control achieved with ERAS is well received by patients.
      Within our ERAS group, a significant portion of patients (22%) had a history of illicit IVDU. We hypothesized that the nonopioid components of an ERAS protocol would prove beneficial for patients who likely have a tolerance to opioid medications. Although subgroup analysis revealed that although these patients had reduction in opioid analgesic use on postoperative day zero, there was no difference between ERAS and control groups in the subsequent days. Unfortunately, our results reveal that ERAS may not have a notable effect with opioid use in these patients. We continue to use ERAS in IVDU patients, however, because there is some evidence that suggests appropriate treatment of pain and addiction in these patients decreases opioid withdrawal symptoms and the number of patients who leave against medical advice.
      • Ray V.
      • Waite M.R.
      • Spexarth F.C.
      • Korman S.
      • Berget S.
      • Kodali S.
      • et al.
      Addiction management in hospitalized patients with intravenous drug use-associated infective endocarditis.
      Similar to ERAS principles, the authors suggest a perioperative strategy to adequately treat postoperative pain and addiction, which begins with consultation of specialists in pain management and addiction medicine on admission.
      • Ray V.
      • Waite M.R.
      • Spexarth F.C.
      • Korman S.
      • Berget S.
      • Kodali S.
      • et al.
      Addiction management in hospitalized patients with intravenous drug use-associated infective endocarditis.
      These findings present an opportunity to improve outcomes in patients with a history of addiction and substance use.
      • Ray V.
      • Waite M.R.
      • Spexarth F.C.
      • Korman S.
      • Berget S.
      • Kodali S.
      • et al.
      Addiction management in hospitalized patients with intravenous drug use-associated infective endocarditis.

      Study Limitations

      Our study represents a single-center experience and therefore may not be generalizable to other institutions. The retrospective design reduces our ability to understand adjustments or deviations from the ERAS protocol made in real-time by bedside providers. For example, the decision on whether to start, continue, or discontinue ketorolac varied among different surgeons and critical care physicians. In addition, with the current analysis, it is difficult to discern how much of the other ERAS protocol components contributed to the results; the protocol encouraged early chest tube removal, for instance, the final decision on timing of drain removal was left to the discretion of the attending surgeon. Because chest tube removal likely has a beneficial effect on pain control, it is possible that this aspect contributed to differing degrees of opioid use. Although we primarily attribute the reduction in opioid requirements to the multimodal pain protocol, it is possible that a Hawthorne Effect impacted provider's prescribing patterns during the postoperative period. Finally, the predischarge patient surveys were not collected in the control group, and thus we are unable to directly compare patient perception between the ERAS and pre-ERAS groups. Nonetheless, our results demonstrate that an ERAS protocol is associated with a significant reduction in overall opioid use in the perioperative period without compromising patient perception of pain control.

      Conclusions

      ERAS protocols with an emphasis on multimodal pain management throughout perioperative care are associated with a significant reduction in the postoperative use of opioid analgesics. Patients with a history of IVDU may not have as pronounced a reduction in opioid use but likely benefit from the nonopioid analgesic regimen. Patients may benefit from future studies analyzing the effects of other ERAS protocol components beyond pain management aspects.

      Webcast

      Conflict of Interest Statement

      The authors reported no conflicts of interest.
      The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

      Appendix E1

      Figure thumbnail fx4
      Figure E1Repeated-measures analysis. ERAS, Enhanced Recovery After Surgery; CI, confidence interval.
      Table E1Morphine milligram equivalent conversion factors for common opioid medications
      OpioidConversion factor
      Codeine0.15
      Fentanyl (IV)0.1
      Hydrocodone1
      Hydromorphone4
      Morphine1
      Oxycodone1.5
      IV, Intravenous.
      Table E2Pre–Enhanced Recovery After Surgery versus Enhanced Recovery After Surgery multivariable quantile (median) regression analysis by postoperative day
      Morphine milligram equivalents by POD
      POD 0POD 1POD 2POD 3POD 4POD 5
      Pre- (Ref) vs Post-ERAS, (95% CI, P value)–148.8 (–183.8 to –113.8), <.0001–25.6 (–36.7 to –14.6), <.0001–17.6 (–25.6 to –9.6), <.0001–16 (–23.1 to –8.9), <.0001–15.9 (–23 to –8.9), <.0001–21.6 (–28.4 to –14.9), <.0001
      Patient characteristics (95% CI, P value)
       Procedure type
      Ascending aorticRefRefRefRefRefRef
      CABG–18.1 (–85.4-49.1), .5970.3 (–21-21.6), .977–7.5 (–22.9-7.8), .336–3.8 (–17.5-9.9), .584–2.6 (–16.5-11.3), .714–5.1 (–18.2-7.9), .438
      Valve–11.6 (–68.2-45), .687–6.4 (–24.2-11.4), .483–13.3 (–26.2-0.4), .043–15.6 (–27- –4.1), .008–5.2 (–16.6-6.1), .362–3.7 (–14.2-6.8), .487
      Valve + CABG–27.0 (–108-54.0), .5128.7 (–17-34.5), .5055.9 (–12.7-24.6), .5313.6 (–13.3-20.5), .674–9.1 (–25.6-7.3), .277–5.4 (–21.2-10.4), .504
      Other–21.4 (–89.2-46.4), .5354.3 (–17.2-25.8), .6978.7 (–6.8-24.1), .27211 (–2.7-24.7), .11714.3 (0.8-27.7), .0387.3 (–4.7-19.3), .232
       No endocarditis (Ref) vs endocarditis3.2 (–54.2-60.7), .9126.8 (–11.4-4.9), .46428.8 (15.7-42), <.00017.6 (–4-19.3), .1997.8 (–3.5-19.1), .1756.6 (–3.5-16.7), .199
       No hypertension (Ref) vs hypertension17.7 (–24.1-59.6), .405–10.4 (–23.9-3), .127–5.1 (–14.7-.5), .300–7.7 (–16.3-0.8), .075–7.9 (–16.3-0.4), .063–5.8 (–13.6-2.1), .152
       NIVDU (Ref) vs IVDU53.7 (–0.4-107.7), .05234.9 (17.9-51.9), <.000112.1 (–0.4-24.5), .05715.5 (4.3-26.8), .00715.6 (4.7-26.5), .00520.2 (10.2-30.1), <.0001
       No liver disease (Ref) vs Liver disease–6.0 (–76.6-64.6), .86817.4 (–4.8-39.5), .1255.8 (–10.3-21.8), .4834.9 (–9.4-19.2), .5051.0 (–13.7-13.8), .992–0.9 (–13.2-11.4), .886
       Cardiac presentation
      Anginal equivalentRefRefRefRefRefRef
      Stable angina52.0 (–106.5-210.5), .519–14.9 (–65.2-35.4), .561–4.2 (–40.3-32), .821–11.7 (–43.8-20.3), .47213.6 (–27.1-54.2), .51327.1 (–8.4-62.7), .134
      Unstable angina39.6 (–105.5-184.8), .592–7 (–52.5-38.6), .7632.8 (–30.3-35.8), .869–0.3 (–29.6-29), .98622.7 (–15.3-60.7), .24220 (–12.5-52.6), .227
      Non-ST elevation49.6 (–120.2-219.5), .5666.4 (–46.9-59.7), .8136 (–32.6-44.6), .7602.6 (–31.6-36.8), .88223.5 (–18.4-65.5), .27128.8 (–7.4-65), .119
      ST-elevation MI71.4 (–169.3-312.1), .560–4.2 (–79.6-71.3), .913–0.8 (–55.5-53.9), .978–10.7 (–59.2-37.8), .66513.6 (–44.3-71.5), .64522.5 (–39-84.1), .472
      Asymptomatic31.5 (–117.4-180.5), .677–14.3 (–61-32.3), .546–5.7 (–39.6-28.2), .741–11.5 (–41.5-18.6), .45317.3 (–20.7-55.3), .37215.4 (–17.6-48.4), .359
      Other39.4 (–100.5-179.4), .580–12 (-55.9-31.9), .591–2.9 (–34.8-28.9), .8560.1 (–28.1-28.4), .99320.2 (–16.1-56.5), .27417.3 (–13.6-48.1), .271
       Intraoperative times (min)
      CPB–0.2 (–0.6-0.3), .487–0.02 (–0.2-0.1), .775–0.03 (–0.1-0.1), .6720.01 (–0.1-0.1), .8620.01 (–0.1-0.1), .8750.03 (–0.1-0.1), .545
      Crossclamp0.1 (–0.5-0.8), .6550.04 (–0.2-0.2), .719–0.03 (–0.2-0.1), .721–0.03 (–0.2-0.1), .620–0.01 (–0.1-0.1), .863–0.1 (–0.2-0.1), .347
      POD, Postoperative day; ERAS, Enhanced Recovery After Surgery; CI, confidence interval; CABG, coronary artery bypass grafting; NIVDU, nonintravenous drug use; IVDU, intravenous drug use; MI, myocardial infarction; CPB, cardiopulmonary bypass.
      Table E3Enhanced Recovery After Surgery multimodal pain medication patient compliance
      MedicationsCompliance, n (%)
      Preoperative
       Acetaminophen152 (60.8)
       Gabapentin152 (60.8)
      Intraoperative
       Liposomal bupivacaine214 (85.6)
      Postoperative
       Dexmedetomidine176 (70.4)
       Acetaminophen248 (99.2)
       Lidocaine patches248 (99.2)
       Gabapentin228 (91.2)
       Tramadol235 (94.0)
       Oxycodone245 (98.0)
       IV fentanyl/hydromorphone246 (98.4)
      IV, Intravenous.
      Table E4Patient characteristics in intravenous drug user (IVDU) versus nonintravenous drug user (NIVDU)
      Characteristics, n (%)NIVDU (393)IVDU (73)P value
      Procedure type<.0001
       Ascending aortic75 (19.08)8 (10.96)
       CABG153 (38.93)17 (23.29)
       Valve107 (27.23)12 (16.44)
       Valve + CABG23 (5.85)1 (1.37)
       Other35 (8.91)35 (47.95)
      Age, median (Q1, Q3)64 (57, 71)44 (34, 60)<.0001
      Gender.008
       Male277 (70.48)40 (54.79)
       Female116 (29.52)33 (45.21)
      Race.16
       White342 (87.02)59 (80.82)
       Non-White51 (12.98)14 (19.18)
      Risk factors
       BMI, median (Q1, Q3)29.85 (26.02, 34.27)25.77 (22.77, 30.94).0001
       Diabetes161 (40.97)13 (17.81)<.0001
       Endocarditis32 (8.14)40 (54.79)<.0001
       Cerebrovascular disease67 (17.05)16 (21.92).318
       Chronic lung disease102 (25.95)15 (20.55).328
       Family history of CAD11 (2.80)1 (1.37).701
       Hypertension326 (82.95)31 (42.47)<.0001
       Last HbA1c level, median (Q1, Q3)6 (5.5, 7)5.7 (5.4, 6.5).0282
       Liver disease8 (2.04)28 (38.36)<.0001
       Peripheral artery disease57 (14.50)6 (8.22).149
      Previous cardiac interventions
       Any145 (36.90)28 (38.36).813
       CABG6 (1.53)1 (1.37)>.999
       Valve36 (9.16)14 (19.18).011
       Other cardiac surgery52 (13.23)12 (16.44).465
       PCI83 (21.12)11 (15.07).237
      Preoperative cardiac status
       Prior MI78 (19.85)12 (16.44).687
       Heart failure121 (30.79)13 (17.81).024
       Cardiogenic shock2 (0.51)1 (1.37).401
       Cardiac arrhythmia89 (22.65)12 (16.44).237
      Operative times (min)
       CPB, median (Q1, Q3)138 (105, 184)117 (86, 155).0043
       Crossclamp, median (Q1, Q3)97 (74, 136)82 (61, 117).0027
      CABG, Coronary artery bypass grafting; BMI, body mass index; CAD, coronary artery disease; HbA1c, hemoglobin A1c; PCI, percutaneous coronary intervention; MI, myocardial infarction; CPB, cardiopulmonary bypass.
      Table E5Pre–Enhanced Recovery After Surgery versus Enhanced Recovery After Surgery (ERAS) opioid analgesic use by repeated measures multivariable design
      MME over time (95% CI, P value)
      Pre-ERAS (Reference) vs Post-ERAS–24.4 (–29.2-19.5), <.0001
      Morphine equivalents (0-5 d)
       Day 0Ref
       Day 1–98 (–112 to –84), <.0001
       Day 2–118.9 (–132.6 to –105.2), <.0001
       Day 3–128.4 (–142.2 to –114.7), <.0001
       Day 4–133.3 (–147 to –119.7), <.0001
       Day 5–133.7 (-147.3 to –120.1), <.0001
      Procedure type
       Ascending aorticRef
       CABG–4.3 (–13.8-5.2), 0.377
       Valve–4.7 (–11.6-2.2), 0.180
       Valve + CABG1.6 (–14.6-17.7), 0.851
       Other7.3 (–4.6-19.2), 0.227
      No endocarditis (Ref) vs ENDOCARDITIS8 (–1.3-17.2), 0.091
      No hypertension (Ref) vs Hypertension–7 (–13.9 to –0.03), 0.049
      NIVDU (Ref) vs IVDU22.9 (11.8-34.1), <.0001
      No liver disease (Ref) vs liver disease4.8 (–12.3-21.9), 0.584
      Cardiac presentation
       Anginal equivalentRef
       Stable angina–2.6 (–22.5-17.3), 0.796
       Unstable angina1.9 (–18.2-22), 0.854
       Non-ST elevation MI6.1 (–19.3-31.5), 0.636
       ST-elevation MI2.3 (–28.7-33.3), 0.886
       Asymptomatic–6.7 (–27.3-14), 0.526
       Other–3.1 (–23.1-17), 0.765
      Intraoperative times (min)
       CPB0.01 (–0.1-0.1), 0.804
       Crossclamp–0.03 (–0.1-0.1), 0.551
      MME, Morphine milligram equivalent; CI, confidence interval; CABG, coronary artery bypass grafting; NIVDU, nonintravenous drug user; IVDU, intravenous drug user; MI, myocardial infarction; CPB, cardiopulmonary bypass.

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      Linked Article

      • Commentary: Better late than never to optimize pain management in cardiac surgery
        JTCVS OpenVol. 12
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          Pain management is a vital component of perioperative care for the cardiac surgical patient. Studies suggest that the overwhelming majority of patients routinely experience moderate-to-severe pain with cough or movement following cardiac surgery, and adequacy of pain management represents one of the few potentially modifiable risk factors that predict one's health care quality of life following cardiac surgery.1,2 Despite the fast-track cardiac surgery era, which reduced the magnitude of opioids administered for cardiac surgery,3 opioids generally remain the primary agents to combat perioperative pain.
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