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The Hemodynamic Effect of Epinephrine-Containing Local Infiltration Analgesia After Tourniquet Deflation During Total Knee Arthroplasty: A Retrospective Observational Study
The Journal of Arthroplasty xxx (2019) 1e6
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The Hemodynamic Effect of Epinephrine-Containing Local Infiltration Analgesia After Tourniquet Deflation During Total Knee Arthroplasty: A Retrospective Observational Study Seokha Yoo, MD a, Jae-Yeon Chung, MD a, Du Hyun Ro, MD b, Hyuk-Soo Han, MD, PhD b, Myung Chul Lee, MD, PhD b, Jin-Tae Kim, MD, PhD a, * a
Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea Department of Orthopedic Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 13 June 2019 Received in revised form 25 July 2019 Accepted 22 August 2019 Available online xxx
Background: Local infiltration analgesia (LIA) is widely used in patients undergoing total knee arthroplasty and often contains epinephrine for a prolonged analgesic effect and to reduce systemic absorption of the local anesthetic. This retrospective observational study investigated the hemodynamic effect of locally infiltrated epinephrine after deflation of the tourniquet during total knee arthroplasty. Methods: We reviewed the electronic medical records of patients who underwent total knee arthroplasty between January 2017 and February 2018 at a tertiary care university hospital. Total knee arthroplasty was performed using a conventional technique with a pneumatic tourniquet. LIA consisted of ropivacaine, morphine sulfate, ketorolac, and methylprednisolone. The patients were grouped according to whether or not epinephrine was included in the LIA. The incidence of a hypertensive response (systolic blood pressure >160 mmHg or mean blood pressure >110 mmHg) after deflation of the tourniquet was compared between the 2 groups. Results: A total of 452 patients had received LIA with (n ¼ 188) or without (n ¼ 264) epinephrine. A hypertensive response after deflation of the tourniquet was more common in patients who received LIA containing epinephrine (42/188 [22.3%]) than in those who received LIA without epinephrine (14/264 [5.3%], P < .001). However, the incidence of hypotension after deflation of the tourniquet was not significantly different between the 2 groups (P ¼ .976). Conclusion: Because epinephrine-containing LIA can result in a hypertensive response after deflation of the tourniquet during total knee arthroplasty, it should be cautiously administered, especially in patients with cardiovascular comorbidities. © 2019 Elsevier Inc. All rights reserved.
Keywords: epinephrine hemodynamics local infiltration analgesia total knee arthroplasty hypertension hypotension
Local infiltration analgesia (LIA) is a simple and effective modality for reducing postoperative pain in patients undergoing total knee arthroplasty (TKA) [1e3]. Epinephrine is often included in LIA
Funding Disclosure: Support for this research was provided solely from institutional and departmental sources (Seoul National University, South Korea grant No. 800-20180131). No author associated with this paper has disclosed any potential or pertinent conflicts which may be perceived to have impending conflict with this work. For full disclosure statements refer to https://doi.org/10.1016/j.arth.2019.08.050. * Reprint requests: Jin-Tae Kim, MD, PhD, Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Daehak-ro 101, Jongno-gu, Seoul 03080, South Korea. https://doi.org/10.1016/j.arth.2019.08.050 0883-5403/© 2019 Elsevier Inc. All rights reserved.
to reduce systemic absorption of the local anesthetic and prolong the analgesic effect [2,4]. However, local infiltration of epinephrine can have serious cardiopulmonary complications, including ventricular tachycardia [5], pulmonary edema [6,7], and stress-induced cardiomyopathy [8,9]. Intraventricular hemorrhage caused by submucosal infiltration of epinephrine has even been reported in a young patient [10]. Therefore, vigilant hemodynamic monitoring is needed when using LIA containing epinephrine. A pneumatic tourniquet is usually used during TKA to reduce intraoperative bleeding and improve the surgical field. However, acute hypotension and a decrease in pH often occur after deflation of the tourniquet because of release of metabolites from the ischemic limb and reduced cardiac preload [11]. When using LIA containing epinephrine, the locally injected epinephrine itself can
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be absorbed in the systemic circulation after deflation of the tourniquet. Most patients who undergo TKA are elderly and have multiple comorbidities [12,13], and epinephrine-related side effects may be associated with adverse cardiopulmonary complications which may be fatal in rare cases. Although a previous retrospective study concluded that LIA was not associated with intraoperative cardiovascular adverse events [14], it focused only on bradycardia and hypotension, not epinephrine-related side effects such as tachycardia and hypertension. Furthermore, the hemodynamic effects of LIA containing epinephrine have not been well studied. The purpose of this study is to assess the hemodynamic effects of LIA containing epinephrine by comparing the hemodynamic changes that occur after deflation of the tourniquet between patients receiving LIA without epinephrine and those receiving LIA with epinephrine during TKA. We hypothesized that the epinephrine included in LIA would lead to a higher incidence of hypertensive episodes after deflation of the tourniquet in patients undergoing TKA. Materials and Methods The study protocol was approved by the institutional review board of Seoul National University Hospital (No. 1804-066-937). The requirement for informed consent was waived by the institutional review board in view of the retrospective nature of the study and the anonymity of the data. This retrospective observational study adheres to the applicable Strengthening The Reporting of OBservational studies in Epidemiology guidelines. Study Population A total of 528 patients who underwent TKA from January 2017 to February 2018 at Seoul National University Hospital were included in the study. Fifty-seven patients who underwent revision TKA surgery, 16 with incomplete data, and 3 who underwent simultaneous bilateral TKA were excluded. Patients who underwent staged bilateral TKAs within 1 week’s interval remained eligible. Patients were grouped according to whether epinephrine was included in the regimen for LIA. During the study period, all TKA procedures were performed by 3 orthopedic surgeons, 2 of whom used LIA containing epinephrine and 1 used LIA without epinephrine. Anesthetic and Surgical Procedure All patients received spinal or general anesthesia for TKA. Spinal anesthesia was performed in the lateral decubitus position using 0.5% hyperbaric bupivacaine mixed with fentanyl citrate 20 mg. Dexmedetomidine or midazolam was administered for intraoperative sedation. In patients who had a contraindication to spinal anesthesia, those in whom spinal anesthesia was unsuccessful, and those who refused spinal anesthesia, general anesthesia was provided by propofol 1-1.5 mg/kg for induction, and sevoflurane or desflurane with a continuous infusion of remifentanil by targetcontrolled infusion pump for maintenance. Some of the patients received a continuous femoral nerve block using 0.2% ropivacaine for postoperative analgesia while others received fentanyl-based intravenous patient-controlled analgesia. TKA was performed using a conventional technique. In all patients, a pneumatic tourniquet was applied on the ipsilateral thigh before the incision and inflated up to 300 mmHg. Before the final components were inserted, LIA solution was injected into the anterior and posterior joint capsule, femoral and tibial periosteal space, the patellar periosteum, the retinaculum, fat pad, and surrounding subcutaneous tissue, with aspiration before each
injection to avoid intravascular administration. The LIA regimen was as follows: ropivacaine 180 mg, morphine sulfate 5 mg, ketorolac 30 mg, cefazolin 1 g, and methylprednisolone 40 mg with or without epinephrine 600 mg. The total volume of LIA solution was 60 mL. After fixation of all prostheses with cement, the pneumatic tourniquet was deflated. Data Collection We reviewed the electronic medical records of the study participants and collected the following data: age, sex, height, weight, body mass index, American Society of Anesthesiologists physical status, comorbidities including hypertension, diabetes, cerebrovascular disease, and coronary artery disease, and preoperative medications, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, b-blockers, and calcium channel blockers. Intraoperative variables included type of anesthesia, total anesthetic time, tourniquet time, estimated blood loss, and urine output. We also recorded the hemodynamic parameters, including systolic blood pressure (SBP), mean blood pressure, and heart rate at the following 5 time points: on arrival in the operating room, 5 minutes before deflation of the tourniquet, immediately, and 5, 10, and 15 minutes after deflation of the tourniquet. We also collected the following postoperative data: hospital length of stay, incidence of complications such as dysrhythmia, myocardial injury, delirium, pulmonary edema, and cerebrovascular accident including ischemic stroke and cerebral hemorrhage, need for admission to the intensive care unit, and inhospital mortality. Myocardial injury was determined by the serum highsensitivity troponin I concentration that was measured in patients with symptoms of cardiac ischemia and defined as an absolute high-sensitivity cardiac troponin I increase of 16 ng/L (99th percentile upper reference limit in Abbott ARCHITECT (Abbott Park, IL) [15]. Postoperative delirium was assessed by psychiatrists in patients with cognitive impairment or abnormal neuropsychiatric behavior after surgery. A cerebrovascular accident was confirmed by brain magnetic resonance imaging. Outcome Variables The primary outcome of the study was the difference in incidence of a hypertensive response after deflation of the tourniquet between patients who received LIA with epinephrine and those who received LIA without epinephrine during TKA. The hypertensive response was defined as an SBP >160 mmHg or a mean blood pressure >110 mmHg [16]. We also evaluated the incidence of hypotension (SBP <90 mmHg or mean blood pressure <60 mmHg) and tachycardia (heart rate >100 beats per minute) after deflation of the tourniquet. The incidence of other complications including dysrhythmia, myocardial injury, pulmonary edema, cerebrovascular accident, and surgical site infection requiring surgical intervention was also compared. Statistical Analysis The sample size was based on the available data from all patients who underwent TKA at our institution during the study period, not on a priori power analysis. The data were tested for normality and are presented as the mean ± standard deviation or median (interquartile range) for continuous variables and as the number (percentage) for categorical variables. An independent samples t-test or Mann-Whitney U test was used to compare continuous variables and the chi-square
S. Yoo et al. / The Journal of Arthroplasty xxx (2019) 1e6
test or Fisher exact test for categorical variables. Bonferroni correction was applied for multiple comparisons. Logistic regression analysis was performed to evaluate the association between use of epinephrine with LIA and the likelihood of a hypertensive response after deflation of the tourniquet. We used the enter method to adjust for other variables, including age, sex, body mass index, American Society of Anesthesiologists physical status, comorbidities, preoperative medications, type of anesthesia, type of sedative, tourniquet time, estimated blood loss, intraoperative urine output, and whether or not the patient received staged bilateral TKA. All analyses were performed using R software version 3.5.1 (R Foundation for Statistical Computing, Vienna, Austria). All tests were 2-tailed, and a P < .05 was considered statistically significant.
Table 2 Incidences of Hemodynamic Instabilities After Deflation of the Tourniquet.
Systolic BP >160 mmHg or mean BP >110 mmHg Systolic BP >190 mmHg or mean BP >140 mmHg Systolic BP increase of 20% from baseline Systolic BP <90 mmHg or mean BP <60 mmHg Tachycardia
LIA Without Epinephrine (N ¼ 264)
LIA With Epinephrine (N ¼ 188)
P
14 (5.3)
42 (22.3)
<.001
0 (0.0)
14 (7.4)
<.001
5 (1.9)
20 (10.6)
<.001
83 (31.4)
58 (30.9)
.976
0 (0.0)
6 (3.2)
.005a
Data are presented as number (%). BP, blood pressure; LIA, local infiltration analgesia. a Fisher exact test.
Results A total of 452 patients who received LIA with (n ¼ 264) or without (n ¼ 188) epinephrine were analyzed. The patient characteristics are presented in Table 1. Nearly 90% of the included patients were female. The incidence of hemodynamic instability, including a hypertensive response, hypotension, and tachycardia, after deflation of the tourniquet is shown in Table 2. A hypertensive response after deflation of the tourniquet occurred more often in patients receiving LIA containing epinephrine (42/188 [22.3%]) than in those receiving LIA without epinephrine (14/264 [5.3%], P < .001, Table 2). Table 1 Patient Characteristics.
Age (y) Sex Female Male Height (cm) Weight (kg) BMI (kg/m2) ASA physical status I II III Comorbidities Hypertension Diabetes Cerebrovascular disease Coronary artery disease Preoperative medication history ARB/ACE inhibitor b-Blocker Calcium channel blocker Preoperative hemoglobin (g/dL) Type of anesthesia General anesthesia Neuraxial anesthesia Type of sedative Dexmedetomidine Midazolam Anesthetic time (min) Tourniquet time (min) Estimated blood loss (mL) Intraoperative urine output (mL) Staged bilateral TKA
3
LIA Without Epinephrine (N ¼ 264)
LIA With Epinephrine (N ¼ 188)
73 (69-77)
71 (67-76)
240 24 154 63 26.5
(90.9) (9.1) (150-157) (57-70) (24.5-28.9)
162 26 153 63 26.2
(86.2) (13.8) (150-158) (56-70) (24.2-29.0)
P
.041 .152
.834 .862 .772 .002
412 (15.5) 214 (81.1) 9 (3.4)
47 (25.0) 126 (67.0) 15 (8.0)
159 51 28 24
(60.2) (19.3) (10.6) (9.1)
112 50 24 19
(59.6) (26.6) (12.8) (10.1)
.966 .086 .576 .841
120 28 93 12.7
(45.5) (10.6) (35.2) (11.9-13.6)
79 24 56 12.9
(42.0) (12.8) (29.8) (12.1-13.8)
.530 .576 .267 .116 .325
15 (5.7) 249 (94.3)
16 (8.6) 172 (91.5)
236 28 135 46 300 300 122
168 20 145 60 300 300 62
Discussion
>.999 (89.4) (10.6) (125-145) (40-55) (150-400) (150-500) (46.2)
(89.4) (10.6) (130-155) (55-65) (200-350) (150-490) (33.0)
However, the incidence of hypotension after deflation of the tourniquet was comparable between the study groups (P ¼ .976, Table 2). The results of the logistic regression analyses are presented in Table 3. After adjustment, LIA containing epinephrine was found to be associated with a higher risk of a hypertensive response after deflation of the tourniquet (odds ratio, 8.09; 95% confidence interval, 3.74-17.5; P < .001; Table 3). In contrast, preoperative administration of a calcium channel blocker and a longer tourniquet time reduced the risk of a hypertensive response after deflation of the tourniquet (Table 3). Figure 1 shows the changes in hemodynamic parameters, including SBP, mean blood pressure, and heart rate, at 5-minute intervals from 5 minutes before to 15 minutes after deflation of the tourniquet. After deflation, there were significant betweengroup differences in SBP, mean blood pressure, and heart rate (Fig. 1). There was no significant between-group difference in the postoperative complication rate, although the incidence rates were very low (Table 4). The hospital length of stay was not significantly different between the groups.
<.001 <.001 .971 .991 .006
Data are presented as mean ± standard deviation, median (interquartile range), or number (%). ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; ASA, American Society of Anesthesiologists; BMI, body mass index; LIA, local infiltration analgesia; TKA, total knee arthroplasty.
We found that a hypertensive response after deflation of the tourniquet was more common in patients receiving LIA containing epinephrine and that the incidence of hypotension was not significantly different between the groups receiving LIA with or without epinephrine. LIA has been shown to be effective for relieving early postoperative pain after TKA [2]. It has been reported that LIA provides a superior analgesia compared with placebo [17,18]. In addition, there might be an additive analgesic effect even when LIA was added to a standardized multimodal regimen including adductor canal block [19]. Given that multimodal analgesia has become the standard of care for patients undergoing joint arthroplasty [20], use of LIA is expected to increase in these patients. Furthermore, LIA appears to be preferred because it is an analgesic modality that can be administered by the surgeon intraoperatively. Since introduction of LIA [21], most of the LIA protocols have included epinephrine to minimize systemic absorption of local anesthetics and to prolong the duration of analgesic effect [2,4]. However, in addition to the risk of a hypertensive response after deflation of the tourniquet, use of epinephrine may increase the risk of tissue ischemia and infection [22e24]. Skin necrosis after infiltration of epinephrine has been reported in previous literature,
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Table 3 Factors Associated With a Hypertensive Response After Deflation of the Tourniquet in Patients Who Received LIA. Crude
LIA containing epinephrine Age (per 10 y) Male BMI (per 1 kg/m2) ASA physical status I II III Comorbidities Hypertension Diabetes Cerebrovascular disease Coronary artery disease Preoperative medication ARB/ACE inhibitor b-Blocker Calcium channel blocker Type of anesthesia General anesthesia Neuraxial anesthesia Sedation using dexmedetomidine Tourniquet time (per 10 min) Estimated blood loss (per 100 mL) Intraoperative urine output (per 100 mL) Staged bilateral TKA
Adjusted
Odds Ratio
95% Confidence Interval
P
Odds Ratio
95% Confidence Interval
P
5.14 0.96 1.40 1.01
2.71-9.73 0.63-1.46 0.62-3.17 0.93-1.10
<.001 .851 .413 .730
8.09 1.02 1.58 1.03
3.74-17.5 0.63-1.64 0.61-4.05 0.93-1.13
<.001 .947 .345 .602
Reference 0.80 2.11
0.40-1.60 0.70-6.38
.523 .186
Reference 1.36 3.54
0.57-3.24 0.84-14.9
.494 .085
0.88 0.83 0.91 0.50
0.50-1.54 0.41-1.67 0.37-2.25 0.15-1.69
.646 .604 .843 .266
0.87 0.71 0.86 0.33
0.38-1.97 0.32-1.60 0.31-2.37 0.08-1.39
.737 .413 .768 .132
1.12 1.33 0.40
0.64-1.96 0.59-3.00 0.20-0.82
.699 .487 .012
1.65 1.99 0.32
0.74-0.67 0.74-5.35 0.14-0.74
.221 .173 .008
Reference 2.13 2.26 1.01 0.86 1.03 0.66
0.49-9.20 0.68-7.55 0.83-1.22 0.71-1.05 0.94-1.12 0.36-1.19
.309 .183 .950 .147 .539 .166
Reference 1.64 1.62 0.72 0.86 1.08 0.86
0.12-23.2 0.19-13.7 0.53-0.97 0.69-1.07 0.97-1.20 0.44-1.68
.713 .660 .030 .180 .181 .659
ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; ASA, American Society of Anesthesiologists; BMI, body mass index; LIA, local infiltration analgesia; TKA, total knee arthroplasty.
even requiring skin graft surgery in 1 case [22]. Another study demonstrated that addition of epinephrine to the LIA mixture did not improve analgesia when compared to use of LIA alone [25]. Therefore, addition of epinephrine should be considered carefully in terms of the risks and benefits on a case-by-case basis. In a previous study comparing hemodynamic parameters after injection of LIA with and without epinephrine, there were significant differences in heart rate and mean arterial pressure at 5 minutes after injection but not at 15 minutes [26]. In contrast, SBP and heart rate were significantly higher even at 15 minutes after deflation of the tourniquet in our study. This may reflect the different dose of injected epinephrine and use of a tourniquet. Although we did not investigate hemodynamic changes for more than 15 minutes after deflation of the tourniquet, vigilant hemodynamic monitoring should be maintained for at least 15 minutes, considering that epinephrine has a half-life of a few minutes. The systemic response to epinephrine has been well described in patients undergoing endoscopic nasal and dental surgery, in whom epinephrine is administered via highly vascular mucosa [27,28]. However, epinephrine included in LIA is injected into paraarticular spaces with relatively low blood flow. Nevertheless, the hypertensive response occurs more frequently in patients receiving LIA containing epinephrine. This may be attributed not only to the high dose of epinephrine (600 mg) administered but also to inadvertent intramuscular injection of the LIA solution. LIA should be injected only into the subcutaneous tissue and periarticular space, but some of the solution may be administered intramuscularly. Blood flow in muscle is greater than that in subcutaneous tissue, so intramuscular injection promotes systemic absorption of injected epinephrine. A previous study that compared plasma concentration of epinephrine after subcutaneous and intramuscular injection reported that the time to peak plasma concentration was significantly shorter after intramuscular injection (8 ± 2 minutes) than after subcutaneous injection (34 ± 14 minutes) [29]. Moreover, epinephrine is mainly inactivated in the liver [30], so locally
injected epinephrine remains unmetabolized in the injected tissue when using a pneumatic tourniquet. Systemic uptake of epinephrine after deflation of the tourniquet can also contribute to abrupt elevation of blood pressure. This phenomenon can complicate anesthetic management. Epinephrine did not reduce the incidence of hypotension after deflation of the tourniquet in this study, indicating that use of epinephrine for LIA has hemodynamic disadvantages in patients undergoing TKA. There are some limitations to be considered when interpreting the results from this study. First, the decision to use epinephrine was made by the surgeon, and there may have been confounding factors that we could not adjust for, for example, technical variations when injecting LIA, such as the depth or direction of needle insertion. Second, the incidence of hemodynamic instability may have been underestimated because we investigated hemodynamic parameters at 5-minute intervals only for 20 minutes around deflation of the tourniquet. However, it is impractical to perform continuous invasive blood pressure monitoring in all patients. Third, the data on the analgesic efficacy of adding epinephrine in LIA, including postoperative pain scores and the duration of analgesia, were unavailable due to the retrospective nature of this study. Without an investigation for analgesic benefits of epinephrine, our findings are still insufficient to suggest omitting epinephrine from LIA in these patients. Lastly, we failed to find any differences in the incidence of postoperative complications, despite the significant differences in hemodynamic change after the administration of LIA. This might be due to a relatively small sample size or lack of clinical implication of the brief hypertensive response to epinephrine-containing LIA. Further large-scale studies on highrisk patients are needed to evaluate the association between the use of epinephrine in LIA and postoperative cardiovascular complications. The literature regarding the association between intraoperative hypertension and postoperative outcomes is mixed [16,31]. However, administration of epinephrine accompanied with deflation of
S. Yoo et al. / The Journal of Arthroplasty xxx (2019) 1e6
Change in SBP (mmHg)
80
*
LIA without epinephrine LIA with epinephrine
40
infiltrated epinephrine on clinical outcomes was not found in this study, clinicians should be aware of intraoperative hemodynamic changes when using LIA containing epinephrine.
* *
Conclusions
0
LIA containing epinephrine can result in a hypertensive response after deflation of the tourniquet during TKA, while the incidence of hypotension after deflation of the tourniquet was not decreased. Although the analgesic efficacy of adding epinephrine in LIA was not evaluated in this study, the use of epinephrinecontaining LIA seems to have a disadvantage in terms of hemodynamics, regardless of potential benefits such as prolonged duration of analgesia. Considering that patients undergoing TKA are usually elderly and may have multiple cardiovascular comorbidities, LIA containing epinephrine should be injected with care and vigilant hemodynamic monitoring.
−40
Change in MBP (mmHg)
−80
Change in HR (bpm)
5
40
**
20 0 −20
References
−40
*
20
10
*
**
*
0
−10
−5 min Tourniquet off +5 min
+10 min
+15 min
Fig. 1. Hemodynamic parameters before and after tourniquet deflation during total knee arthroplasty. *, P < .001 between the 2 groups; **, P < .01 between the 2 groups. HR, heart rate; LIA, local infiltration analgesia; MBP, mean blood pressure; SBP, systolic blood pressure.
a tourniquet can cause abrupt elevation of blood pressure, which may be different from intraoperative hypertension in terms of its effect on perioperative outcomes. Although adverse effect of locally
Table 4 Postoperative Outcomes in Patients Who Received LIA During Total Knee Arthroplasty. LIA Without Epinephrine (N ¼ 264) Composite outcomes Dysrhythmia Postoperative myocardial injury Postoperative delirium Postoperative pulmonary edema Cerebrovascular accidenta Wound infection Inhospital mortality ICU admission Hospital length of stay
LIA With Epinephrine (N ¼ 188)
P
4 (1.5) 1 (0.4) 1 (0.4)
4 (2.1) 0 (0) 2 (1.1)
.724 >.999 .573
0 (0) 1 (0.4)
1 (0.5) 0 (0)
.416 >.999
1 1 0 1 13
(0.4) (0.4) (0) (0.4) (9-16)
2 0 1 5 11
(1.1) (0.0) (0.5) (2.7) (9-17)
.573 >.999 .416 .086 .841
Data are presented as number (%) or median (interquartile range), and Fisher exact test was performed to compare categorical variables. ICU, intensive care unit; LIA, local infiltration analgesia. a Cerebrovascular accident included postoperative ischemic stroke and cerebral hemorrhage.
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[18] Andersen LO, Husted H, Otte KS, Kristensen BB, Kehlet H. High-volume infiltration analgesia in total knee arthroplasty: a randomized, double-blind, placebo-controlled trial. Acta Anaesthesiol Scand 2008;52:1331e5. https:// doi.org/10.1111/j.1399-6576.2008.01777.x. [19] Tziona D, Papaioannou M, Mela A, Potamianou S, Makris A. Local infiltration analgesia combined with a standardized multimodal approach including an adductor canal block in total knee arthroplasty: a prospective randomized, placebo-controlled, double-blinded clinical trial. J Anesth 2018;32:326e32. https://doi.org/10.1007/s00540-018-2476-x. [20] Memtsoudis SG, Poeran J, Zubizarreta N, Cozowicz C, Morwald EE, Mariano ER, et al. Association of multimodal pain management strategies with perioperative outcomes and resource utilization: a population-based study. Anesthesiology 2018;128:891e902. https://doi.org/10.1097/ALN.0000000000002132. [21] Kerr DR, Kohan L. Local infiltration analgesia: a technique for the control of acute postoperative pain following knee and hip surgery: a case study of 325 patients. Acta Orthop 2008;79:174e83. https://doi.org/10.1080/17453670710014950. [22] Hartzell TL, Sangji NF, Hertl MC. Ischemia of postmastectomy skin after infiltration of local anesthetic with epinephrine: a case report and review of the literature. Aesthetic Plast Surg 2010;34:782e4. https://doi.org/10.1007/ s00266-010-9528-4. [23] Toftdahl K, Nikolajsen L, Haraldsted V, Madsen F, Tonnesen EK, Soballe K. Comparison of peri- and intraarticular analgesia with femoral nerve block after total knee arthroplasty: a randomized clinical trial. Acta Orthop 2007;78: 172e9. https://doi.org/10.1080/17453670710013645. [24] Piper SL, Kramer JD, Kim HT, Feeley BT. Effects of local anesthetics on articular cartilage. Am J Sports Med 2011;39:2245e53. https://doi.org/10.1177/ 0363546511402780.
[25] Schotanus MGM, Bemelmans YFL, van der Kuy PHM, Jansen J, Kort NP. No advantage of adrenaline in the local infiltration analgesia mixture during total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc 2017;25:2778e83. https://doi.org/10.1007/s00167-015-3723-4. [26] Karaoglu S, Dogru K, Kabak S, Inan M, Halici M. Effects of epinephrine in local anesthetic mixtures on hemodynamics and view quality during knee arthroscopy. Knee Surg Sports Traumatol Arthrosc 2002;10:226e8. https:// doi.org/10.1007/s00167-001-0257-8. [27] Kaur P, Bahl R, Kaura S, Bansal S. Comparing hemodynamic and glycemic response to local anesthesia with epinephrine and without epinephrine in patients undergoing tooth extractions. Natl J Maxillofac Surg 2016;7:166e72. https://doi.org/10.4103/0975-5950.201370. [28] Pasternak JJ, Atkinson JL, Kasperbauer JL, Lanier WL. Hemodynamic responses to epinephrine-containing local anesthetic injection and to emergence from general anesthesia in transsphenoidal hypophysectomy patients. J Neurosurg Anesthesiol 2004;16:189e95. [29] Simons FE, Roberts JR, Gu X, Simons KJ. Epinephrine absorption in children with a history of anaphylaxis. J Allergy Clin Immunol 1998;101:33e7. https:// doi.org/10.1016/s0091-6749(98)70190-3. [30] Westfall TC, Macarthur H, Westfall DP. Adrenergic agonists and antagonists. In: Brunton LL, Hilal-Dandan R, Knollmann BC, editors. Goodman & Gilman's the Pharmacological basis of Therapeutics. 13th ed. New York, NY: McGrawHill Education; 2017. [31] Reich DL, Bennett-Guerrero E, Bodian CA, Hossain S, Winfree W, Krol M. Intraoperative tachycardia and hypertension are independently associated with adverse outcome in noncardiac surgery of long duration. Anesth Analg 2002;95:273e7.
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The Hemodynamic Effect of Epinephrine-Containing Local Infiltration Analgesia After Tourniquet Deflation During Total Knee Arthroplasty: A Retrospective Observational Study Seokha Yoo, MD a, Jae-Yeon Chung, MD a, Du Hyun Ro, MD b, Hyuk-Soo Han, MD, PhD b, Myung Chul Lee, MD, PhD b, Jin-Tae Kim, MD, PhD a, * a
Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea Department of Orthopedic Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 13 June 2019 Received in revised form 25 July 2019 Accepted 22 August 2019 Available online xxx
Background: Local infiltration analgesia (LIA) is widely used in patients undergoing total knee arthroplasty and often contains epinephrine for a prolonged analgesic effect and to reduce systemic absorption of the local anesthetic. This retrospective observational study investigated the hemodynamic effect of locally infiltrated epinephrine after deflation of the tourniquet during total knee arthroplasty. Methods: We reviewed the electronic medical records of patients who underwent total knee arthroplasty between January 2017 and February 2018 at a tertiary care university hospital. Total knee arthroplasty was performed using a conventional technique with a pneumatic tourniquet. LIA consisted of ropivacaine, morphine sulfate, ketorolac, and methylprednisolone. The patients were grouped according to whether or not epinephrine was included in the LIA. The incidence of a hypertensive response (systolic blood pressure >160 mmHg or mean blood pressure >110 mmHg) after deflation of the tourniquet was compared between the 2 groups. Results: A total of 452 patients had received LIA with (n ¼ 188) or without (n ¼ 264) epinephrine. A hypertensive response after deflation of the tourniquet was more common in patients who received LIA containing epinephrine (42/188 [22.3%]) than in those who received LIA without epinephrine (14/264 [5.3%], P < .001). However, the incidence of hypotension after deflation of the tourniquet was not significantly different between the 2 groups (P ¼ .976). Conclusion: Because epinephrine-containing LIA can result in a hypertensive response after deflation of the tourniquet during total knee arthroplasty, it should be cautiously administered, especially in patients with cardiovascular comorbidities. © 2019 Elsevier Inc. All rights reserved.
Keywords: epinephrine hemodynamics local infiltration analgesia total knee arthroplasty hypertension hypotension
Local infiltration analgesia (LIA) is a simple and effective modality for reducing postoperative pain in patients undergoing total knee arthroplasty (TKA) [1e3]. Epinephrine is often included in LIA
Funding Disclosure: Support for this research was provided solely from institutional and departmental sources (Seoul National University, South Korea grant No. 800-20180131). No author associated with this paper has disclosed any potential or pertinent conflicts which may be perceived to have impending conflict with this work. For full disclosure statements refer to https://doi.org/10.1016/j.arth.2019.08.050. * Reprint requests: Jin-Tae Kim, MD, PhD, Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Daehak-ro 101, Jongno-gu, Seoul 03080, South Korea. https://doi.org/10.1016/j.arth.2019.08.050 0883-5403/© 2019 Elsevier Inc. All rights reserved.
to reduce systemic absorption of the local anesthetic and prolong the analgesic effect [2,4]. However, local infiltration of epinephrine can have serious cardiopulmonary complications, including ventricular tachycardia [5], pulmonary edema [6,7], and stress-induced cardiomyopathy [8,9]. Intraventricular hemorrhage caused by submucosal infiltration of epinephrine has even been reported in a young patient [10]. Therefore, vigilant hemodynamic monitoring is needed when using LIA containing epinephrine. A pneumatic tourniquet is usually used during TKA to reduce intraoperative bleeding and improve the surgical field. However, acute hypotension and a decrease in pH often occur after deflation of the tourniquet because of release of metabolites from the ischemic limb and reduced cardiac preload [11]. When using LIA containing epinephrine, the locally injected epinephrine itself can
2
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be absorbed in the systemic circulation after deflation of the tourniquet. Most patients who undergo TKA are elderly and have multiple comorbidities [12,13], and epinephrine-related side effects may be associated with adverse cardiopulmonary complications which may be fatal in rare cases. Although a previous retrospective study concluded that LIA was not associated with intraoperative cardiovascular adverse events [14], it focused only on bradycardia and hypotension, not epinephrine-related side effects such as tachycardia and hypertension. Furthermore, the hemodynamic effects of LIA containing epinephrine have not been well studied. The purpose of this study is to assess the hemodynamic effects of LIA containing epinephrine by comparing the hemodynamic changes that occur after deflation of the tourniquet between patients receiving LIA without epinephrine and those receiving LIA with epinephrine during TKA. We hypothesized that the epinephrine included in LIA would lead to a higher incidence of hypertensive episodes after deflation of the tourniquet in patients undergoing TKA. Materials and Methods The study protocol was approved by the institutional review board of Seoul National University Hospital (No. 1804-066-937). The requirement for informed consent was waived by the institutional review board in view of the retrospective nature of the study and the anonymity of the data. This retrospective observational study adheres to the applicable Strengthening The Reporting of OBservational studies in Epidemiology guidelines. Study Population A total of 528 patients who underwent TKA from January 2017 to February 2018 at Seoul National University Hospital were included in the study. Fifty-seven patients who underwent revision TKA surgery, 16 with incomplete data, and 3 who underwent simultaneous bilateral TKA were excluded. Patients who underwent staged bilateral TKAs within 1 week’s interval remained eligible. Patients were grouped according to whether epinephrine was included in the regimen for LIA. During the study period, all TKA procedures were performed by 3 orthopedic surgeons, 2 of whom used LIA containing epinephrine and 1 used LIA without epinephrine. Anesthetic and Surgical Procedure All patients received spinal or general anesthesia for TKA. Spinal anesthesia was performed in the lateral decubitus position using 0.5% hyperbaric bupivacaine mixed with fentanyl citrate 20 mg. Dexmedetomidine or midazolam was administered for intraoperative sedation. In patients who had a contraindication to spinal anesthesia, those in whom spinal anesthesia was unsuccessful, and those who refused spinal anesthesia, general anesthesia was provided by propofol 1-1.5 mg/kg for induction, and sevoflurane or desflurane with a continuous infusion of remifentanil by targetcontrolled infusion pump for maintenance. Some of the patients received a continuous femoral nerve block using 0.2% ropivacaine for postoperative analgesia while others received fentanyl-based intravenous patient-controlled analgesia. TKA was performed using a conventional technique. In all patients, a pneumatic tourniquet was applied on the ipsilateral thigh before the incision and inflated up to 300 mmHg. Before the final components were inserted, LIA solution was injected into the anterior and posterior joint capsule, femoral and tibial periosteal space, the patellar periosteum, the retinaculum, fat pad, and surrounding subcutaneous tissue, with aspiration before each
injection to avoid intravascular administration. The LIA regimen was as follows: ropivacaine 180 mg, morphine sulfate 5 mg, ketorolac 30 mg, cefazolin 1 g, and methylprednisolone 40 mg with or without epinephrine 600 mg. The total volume of LIA solution was 60 mL. After fixation of all prostheses with cement, the pneumatic tourniquet was deflated. Data Collection We reviewed the electronic medical records of the study participants and collected the following data: age, sex, height, weight, body mass index, American Society of Anesthesiologists physical status, comorbidities including hypertension, diabetes, cerebrovascular disease, and coronary artery disease, and preoperative medications, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, b-blockers, and calcium channel blockers. Intraoperative variables included type of anesthesia, total anesthetic time, tourniquet time, estimated blood loss, and urine output. We also recorded the hemodynamic parameters, including systolic blood pressure (SBP), mean blood pressure, and heart rate at the following 5 time points: on arrival in the operating room, 5 minutes before deflation of the tourniquet, immediately, and 5, 10, and 15 minutes after deflation of the tourniquet. We also collected the following postoperative data: hospital length of stay, incidence of complications such as dysrhythmia, myocardial injury, delirium, pulmonary edema, and cerebrovascular accident including ischemic stroke and cerebral hemorrhage, need for admission to the intensive care unit, and inhospital mortality. Myocardial injury was determined by the serum highsensitivity troponin I concentration that was measured in patients with symptoms of cardiac ischemia and defined as an absolute high-sensitivity cardiac troponin I increase of 16 ng/L (99th percentile upper reference limit in Abbott ARCHITECT (Abbott Park, IL) [15]. Postoperative delirium was assessed by psychiatrists in patients with cognitive impairment or abnormal neuropsychiatric behavior after surgery. A cerebrovascular accident was confirmed by brain magnetic resonance imaging. Outcome Variables The primary outcome of the study was the difference in incidence of a hypertensive response after deflation of the tourniquet between patients who received LIA with epinephrine and those who received LIA without epinephrine during TKA. The hypertensive response was defined as an SBP >160 mmHg or a mean blood pressure >110 mmHg [16]. We also evaluated the incidence of hypotension (SBP <90 mmHg or mean blood pressure <60 mmHg) and tachycardia (heart rate >100 beats per minute) after deflation of the tourniquet. The incidence of other complications including dysrhythmia, myocardial injury, pulmonary edema, cerebrovascular accident, and surgical site infection requiring surgical intervention was also compared. Statistical Analysis The sample size was based on the available data from all patients who underwent TKA at our institution during the study period, not on a priori power analysis. The data were tested for normality and are presented as the mean ± standard deviation or median (interquartile range) for continuous variables and as the number (percentage) for categorical variables. An independent samples t-test or Mann-Whitney U test was used to compare continuous variables and the chi-square
S. Yoo et al. / The Journal of Arthroplasty xxx (2019) 1e6
test or Fisher exact test for categorical variables. Bonferroni correction was applied for multiple comparisons. Logistic regression analysis was performed to evaluate the association between use of epinephrine with LIA and the likelihood of a hypertensive response after deflation of the tourniquet. We used the enter method to adjust for other variables, including age, sex, body mass index, American Society of Anesthesiologists physical status, comorbidities, preoperative medications, type of anesthesia, type of sedative, tourniquet time, estimated blood loss, intraoperative urine output, and whether or not the patient received staged bilateral TKA. All analyses were performed using R software version 3.5.1 (R Foundation for Statistical Computing, Vienna, Austria). All tests were 2-tailed, and a P < .05 was considered statistically significant.
Table 2 Incidences of Hemodynamic Instabilities After Deflation of the Tourniquet.
Systolic BP >160 mmHg or mean BP >110 mmHg Systolic BP >190 mmHg or mean BP >140 mmHg Systolic BP increase of 20% from baseline Systolic BP <90 mmHg or mean BP <60 mmHg Tachycardia
LIA Without Epinephrine (N ¼ 264)
LIA With Epinephrine (N ¼ 188)
P
14 (5.3)
42 (22.3)
<.001
0 (0.0)
14 (7.4)
<.001
5 (1.9)
20 (10.6)
<.001
83 (31.4)
58 (30.9)
.976
0 (0.0)
6 (3.2)
.005a
Data are presented as number (%). BP, blood pressure; LIA, local infiltration analgesia. a Fisher exact test.
Results A total of 452 patients who received LIA with (n ¼ 264) or without (n ¼ 188) epinephrine were analyzed. The patient characteristics are presented in Table 1. Nearly 90% of the included patients were female. The incidence of hemodynamic instability, including a hypertensive response, hypotension, and tachycardia, after deflation of the tourniquet is shown in Table 2. A hypertensive response after deflation of the tourniquet occurred more often in patients receiving LIA containing epinephrine (42/188 [22.3%]) than in those receiving LIA without epinephrine (14/264 [5.3%], P < .001, Table 2). Table 1 Patient Characteristics.
Age (y) Sex Female Male Height (cm) Weight (kg) BMI (kg/m2) ASA physical status I II III Comorbidities Hypertension Diabetes Cerebrovascular disease Coronary artery disease Preoperative medication history ARB/ACE inhibitor b-Blocker Calcium channel blocker Preoperative hemoglobin (g/dL) Type of anesthesia General anesthesia Neuraxial anesthesia Type of sedative Dexmedetomidine Midazolam Anesthetic time (min) Tourniquet time (min) Estimated blood loss (mL) Intraoperative urine output (mL) Staged bilateral TKA
3
LIA Without Epinephrine (N ¼ 264)
LIA With Epinephrine (N ¼ 188)
73 (69-77)
71 (67-76)
240 24 154 63 26.5
(90.9) (9.1) (150-157) (57-70) (24.5-28.9)
162 26 153 63 26.2
(86.2) (13.8) (150-158) (56-70) (24.2-29.0)
P
.041 .152
.834 .862 .772 .002
412 (15.5) 214 (81.1) 9 (3.4)
47 (25.0) 126 (67.0) 15 (8.0)
159 51 28 24
(60.2) (19.3) (10.6) (9.1)
112 50 24 19
(59.6) (26.6) (12.8) (10.1)
.966 .086 .576 .841
120 28 93 12.7
(45.5) (10.6) (35.2) (11.9-13.6)
79 24 56 12.9
(42.0) (12.8) (29.8) (12.1-13.8)
.530 .576 .267 .116 .325
15 (5.7) 249 (94.3)
16 (8.6) 172 (91.5)
236 28 135 46 300 300 122
168 20 145 60 300 300 62
Discussion
>.999 (89.4) (10.6) (125-145) (40-55) (150-400) (150-500) (46.2)
(89.4) (10.6) (130-155) (55-65) (200-350) (150-490) (33.0)
However, the incidence of hypotension after deflation of the tourniquet was comparable between the study groups (P ¼ .976, Table 2). The results of the logistic regression analyses are presented in Table 3. After adjustment, LIA containing epinephrine was found to be associated with a higher risk of a hypertensive response after deflation of the tourniquet (odds ratio, 8.09; 95% confidence interval, 3.74-17.5; P < .001; Table 3). In contrast, preoperative administration of a calcium channel blocker and a longer tourniquet time reduced the risk of a hypertensive response after deflation of the tourniquet (Table 3). Figure 1 shows the changes in hemodynamic parameters, including SBP, mean blood pressure, and heart rate, at 5-minute intervals from 5 minutes before to 15 minutes after deflation of the tourniquet. After deflation, there were significant betweengroup differences in SBP, mean blood pressure, and heart rate (Fig. 1). There was no significant between-group difference in the postoperative complication rate, although the incidence rates were very low (Table 4). The hospital length of stay was not significantly different between the groups.
<.001 <.001 .971 .991 .006
Data are presented as mean ± standard deviation, median (interquartile range), or number (%). ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; ASA, American Society of Anesthesiologists; BMI, body mass index; LIA, local infiltration analgesia; TKA, total knee arthroplasty.
We found that a hypertensive response after deflation of the tourniquet was more common in patients receiving LIA containing epinephrine and that the incidence of hypotension was not significantly different between the groups receiving LIA with or without epinephrine. LIA has been shown to be effective for relieving early postoperative pain after TKA [2]. It has been reported that LIA provides a superior analgesia compared with placebo [17,18]. In addition, there might be an additive analgesic effect even when LIA was added to a standardized multimodal regimen including adductor canal block [19]. Given that multimodal analgesia has become the standard of care for patients undergoing joint arthroplasty [20], use of LIA is expected to increase in these patients. Furthermore, LIA appears to be preferred because it is an analgesic modality that can be administered by the surgeon intraoperatively. Since introduction of LIA [21], most of the LIA protocols have included epinephrine to minimize systemic absorption of local anesthetics and to prolong the duration of analgesic effect [2,4]. However, in addition to the risk of a hypertensive response after deflation of the tourniquet, use of epinephrine may increase the risk of tissue ischemia and infection [22e24]. Skin necrosis after infiltration of epinephrine has been reported in previous literature,
4
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Table 3 Factors Associated With a Hypertensive Response After Deflation of the Tourniquet in Patients Who Received LIA. Crude
LIA containing epinephrine Age (per 10 y) Male BMI (per 1 kg/m2) ASA physical status I II III Comorbidities Hypertension Diabetes Cerebrovascular disease Coronary artery disease Preoperative medication ARB/ACE inhibitor b-Blocker Calcium channel blocker Type of anesthesia General anesthesia Neuraxial anesthesia Sedation using dexmedetomidine Tourniquet time (per 10 min) Estimated blood loss (per 100 mL) Intraoperative urine output (per 100 mL) Staged bilateral TKA
Adjusted
Odds Ratio
95% Confidence Interval
P
Odds Ratio
95% Confidence Interval
P
5.14 0.96 1.40 1.01
2.71-9.73 0.63-1.46 0.62-3.17 0.93-1.10
<.001 .851 .413 .730
8.09 1.02 1.58 1.03
3.74-17.5 0.63-1.64 0.61-4.05 0.93-1.13
<.001 .947 .345 .602
Reference 0.80 2.11
0.40-1.60 0.70-6.38
.523 .186
Reference 1.36 3.54
0.57-3.24 0.84-14.9
.494 .085
0.88 0.83 0.91 0.50
0.50-1.54 0.41-1.67 0.37-2.25 0.15-1.69
.646 .604 .843 .266
0.87 0.71 0.86 0.33
0.38-1.97 0.32-1.60 0.31-2.37 0.08-1.39
.737 .413 .768 .132
1.12 1.33 0.40
0.64-1.96 0.59-3.00 0.20-0.82
.699 .487 .012
1.65 1.99 0.32
0.74-0.67 0.74-5.35 0.14-0.74
.221 .173 .008
Reference 2.13 2.26 1.01 0.86 1.03 0.66
0.49-9.20 0.68-7.55 0.83-1.22 0.71-1.05 0.94-1.12 0.36-1.19
.309 .183 .950 .147 .539 .166
Reference 1.64 1.62 0.72 0.86 1.08 0.86
0.12-23.2 0.19-13.7 0.53-0.97 0.69-1.07 0.97-1.20 0.44-1.68
.713 .660 .030 .180 .181 .659
ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; ASA, American Society of Anesthesiologists; BMI, body mass index; LIA, local infiltration analgesia; TKA, total knee arthroplasty.
even requiring skin graft surgery in 1 case [22]. Another study demonstrated that addition of epinephrine to the LIA mixture did not improve analgesia when compared to use of LIA alone [25]. Therefore, addition of epinephrine should be considered carefully in terms of the risks and benefits on a case-by-case basis. In a previous study comparing hemodynamic parameters after injection of LIA with and without epinephrine, there were significant differences in heart rate and mean arterial pressure at 5 minutes after injection but not at 15 minutes [26]. In contrast, SBP and heart rate were significantly higher even at 15 minutes after deflation of the tourniquet in our study. This may reflect the different dose of injected epinephrine and use of a tourniquet. Although we did not investigate hemodynamic changes for more than 15 minutes after deflation of the tourniquet, vigilant hemodynamic monitoring should be maintained for at least 15 minutes, considering that epinephrine has a half-life of a few minutes. The systemic response to epinephrine has been well described in patients undergoing endoscopic nasal and dental surgery, in whom epinephrine is administered via highly vascular mucosa [27,28]. However, epinephrine included in LIA is injected into paraarticular spaces with relatively low blood flow. Nevertheless, the hypertensive response occurs more frequently in patients receiving LIA containing epinephrine. This may be attributed not only to the high dose of epinephrine (600 mg) administered but also to inadvertent intramuscular injection of the LIA solution. LIA should be injected only into the subcutaneous tissue and periarticular space, but some of the solution may be administered intramuscularly. Blood flow in muscle is greater than that in subcutaneous tissue, so intramuscular injection promotes systemic absorption of injected epinephrine. A previous study that compared plasma concentration of epinephrine after subcutaneous and intramuscular injection reported that the time to peak plasma concentration was significantly shorter after intramuscular injection (8 ± 2 minutes) than after subcutaneous injection (34 ± 14 minutes) [29]. Moreover, epinephrine is mainly inactivated in the liver [30], so locally
injected epinephrine remains unmetabolized in the injected tissue when using a pneumatic tourniquet. Systemic uptake of epinephrine after deflation of the tourniquet can also contribute to abrupt elevation of blood pressure. This phenomenon can complicate anesthetic management. Epinephrine did not reduce the incidence of hypotension after deflation of the tourniquet in this study, indicating that use of epinephrine for LIA has hemodynamic disadvantages in patients undergoing TKA. There are some limitations to be considered when interpreting the results from this study. First, the decision to use epinephrine was made by the surgeon, and there may have been confounding factors that we could not adjust for, for example, technical variations when injecting LIA, such as the depth or direction of needle insertion. Second, the incidence of hemodynamic instability may have been underestimated because we investigated hemodynamic parameters at 5-minute intervals only for 20 minutes around deflation of the tourniquet. However, it is impractical to perform continuous invasive blood pressure monitoring in all patients. Third, the data on the analgesic efficacy of adding epinephrine in LIA, including postoperative pain scores and the duration of analgesia, were unavailable due to the retrospective nature of this study. Without an investigation for analgesic benefits of epinephrine, our findings are still insufficient to suggest omitting epinephrine from LIA in these patients. Lastly, we failed to find any differences in the incidence of postoperative complications, despite the significant differences in hemodynamic change after the administration of LIA. This might be due to a relatively small sample size or lack of clinical implication of the brief hypertensive response to epinephrine-containing LIA. Further large-scale studies on highrisk patients are needed to evaluate the association between the use of epinephrine in LIA and postoperative cardiovascular complications. The literature regarding the association between intraoperative hypertension and postoperative outcomes is mixed [16,31]. However, administration of epinephrine accompanied with deflation of
S. Yoo et al. / The Journal of Arthroplasty xxx (2019) 1e6
Change in SBP (mmHg)
80
*
LIA without epinephrine LIA with epinephrine
40
infiltrated epinephrine on clinical outcomes was not found in this study, clinicians should be aware of intraoperative hemodynamic changes when using LIA containing epinephrine.
* *
Conclusions
0
LIA containing epinephrine can result in a hypertensive response after deflation of the tourniquet during TKA, while the incidence of hypotension after deflation of the tourniquet was not decreased. Although the analgesic efficacy of adding epinephrine in LIA was not evaluated in this study, the use of epinephrinecontaining LIA seems to have a disadvantage in terms of hemodynamics, regardless of potential benefits such as prolonged duration of analgesia. Considering that patients undergoing TKA are usually elderly and may have multiple cardiovascular comorbidities, LIA containing epinephrine should be injected with care and vigilant hemodynamic monitoring.
−40
Change in MBP (mmHg)
−80
Change in HR (bpm)
5
40
**
20 0 −20
References
−40
*
20
10
*
**
*
0
−10
−5 min Tourniquet off +5 min
+10 min
+15 min
Fig. 1. Hemodynamic parameters before and after tourniquet deflation during total knee arthroplasty. *, P < .001 between the 2 groups; **, P < .01 between the 2 groups. HR, heart rate; LIA, local infiltration analgesia; MBP, mean blood pressure; SBP, systolic blood pressure.
a tourniquet can cause abrupt elevation of blood pressure, which may be different from intraoperative hypertension in terms of its effect on perioperative outcomes. Although adverse effect of locally
Table 4 Postoperative Outcomes in Patients Who Received LIA During Total Knee Arthroplasty. LIA Without Epinephrine (N ¼ 264) Composite outcomes Dysrhythmia Postoperative myocardial injury Postoperative delirium Postoperative pulmonary edema Cerebrovascular accidenta Wound infection Inhospital mortality ICU admission Hospital length of stay
LIA With Epinephrine (N ¼ 188)
P
4 (1.5) 1 (0.4) 1 (0.4)
4 (2.1) 0 (0) 2 (1.1)
.724 >.999 .573
0 (0) 1 (0.4)
1 (0.5) 0 (0)
.416 >.999
1 1 0 1 13
(0.4) (0.4) (0) (0.4) (9-16)
2 0 1 5 11
(1.1) (0.0) (0.5) (2.7) (9-17)
.573 >.999 .416 .086 .841
Data are presented as number (%) or median (interquartile range), and Fisher exact test was performed to compare categorical variables. ICU, intensive care unit; LIA, local infiltration analgesia. a Cerebrovascular accident included postoperative ischemic stroke and cerebral hemorrhage.
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