Eur J Orthop Surg Traumatol DOI 10.1007/s00590-015-1616-3
ORIGINAL ARTICLE • KNEE - ANESTHESIA
Less incidence of coronary artery disease in general anesthesia compared to spinal–epidural anesthesia after total knee replacement: 90-day follow-up period by a population-based dataset Jui-Yang Hsieh1 • Hui-Wen Lin2
Received: 29 September 2014 / Accepted: 24 February 2015 Springer-Verlag France 2015
Abstract Total knee replacement (TKR) is an effective and safe procedure. However, large-scale study to compare the incidence of coronary artery disease (CAD) after spinal or epidural anesthesia (SA–EA) or general anesthesia (GA) for TKR has not ever been conducted. To do so, we studied a population-based dataset from the Taiwan National Health Research Institute and hypothesized that the incidence of CAD might be different with regional than with general anesthesia. The risk of CAD-related events during a 90-day follow-up period among patients who received TKR under SA–EA or GA was evaluated in the present study. A total of 1500 patients from the Taiwan National Health Insurance claims database who underwent TKR from January 1, 2004, to December 31, 2006, were allocated into two groups. Group 1 included 1012 patients who received SA–EA during TKR procedure. Group 2 included 488 patients who received GA during this procedure. The number of patients who developed CAD during the 90-day follow-up period was 31 (3.1 %) in group 1 and 6 (1.2 %) in group 2. The Kaplan–Meier survival analysis of IHDfree cumulative survival rate during the 90-day follow-up period for patients who underwent TKR was significantly lower in group 1 than in group 2. The hazard ratio for the occurrence of CAD was 2.80 (95 % CI 1.16–6.78), and the
& Jui-Yang Hsieh [email protected] Hui-Wen Lin [email protected] 1
Department of Orthopedics, National Taiwan University Hospital and Jinshan Branch, No. 7, Chung-Shan South Road, Taipei 100, Taiwan, ROC
2
Department of Mathematics, Soochow University, 70 Linshi Road, Shihlin, Taipei 111, Taiwan, ROC
hazard was higher for patients who received SA–EA than for patients who received GA after adjusted potential confounding factors. After the performance of TKR, patients had a potentially increased risk for CAD in SA–EA compared to GA during the 90-day follow-up period. Keywords Coronary artery disease General anesthesia Spinal–epidural anesthesia Total knee replacement
Introduction Primary total knee replacement (TKR) is an effective and safe procedure commonly performed for knee joint failure caused by osteoarthritis, rheumatoid arthritis and other types of inflammatory arthritis. Regional anesthesia of spinal or epidural anesthesia (SA–EA) and general anesthesia (GA) are prevalent methods used for such surgery. SA–EA provides excellent anesthesia for many surgical procedures and is associated with multiple benefits compared to GA when used for orthopedic surgery. But like all powerful techniques, a number of complications of SA–EA have long been recognized, including post dural puncture headache (PDPH), backache, transient neurological symptoms, total spinal anesthesia, spinal or epidural hematoma, epidural abscess, meningitis, intracranial bleeding, cauda equina syndrome, arachnoiditis, cardiac arrest, urinary retention and drug toxicity [1–3]. However, large-scale study to compare the incidence of coronary artery disease (CAD) after SA–EA or GA for TKR has not ever been conducted. The aim of the present study was to evaluate the risk of future CAD development among patients who received TKR under SA–EA or GA during the 90-day post-surgical follow-up period. To do so, we hypothesized that the incidence of CAD might be
123
Eur J Orthop Surg Traumatol
different in regional and GA by using a population-based dataset from the Taiwan National Health Research Institute.
Materials and methods The National Health Insurance program has been implemented in Taiwan since 1995, and covers all medical benefit claims of ambulatory care, offers complete freedom of choice among healthcare providers and covers approximately 98 % of the total population of Taiwan. The Longitudinal Health Insurance Database 2005 (LHID 2005) released by the Taiwan National Health Research Institute in 2006 and the original claims data for reimbursement for one million enrollees under the National Health Insurance program were used as a data source. This cohort study was conducted using the LHID 2005. We identified patients who had primary TKR from January 1, 2004, to December 31, 2006, based on the principal procedure code of 81.54 (TKR). Cohort entry was defined as the date when the patients received primary TKR from January 1, 2004, to December 31, 2006. If a patient received primary TKR twice during the 3 years, the latter one was excluded from the cohort study. All patients were followed for 90 days from the date of cohort entry or followed until they developed CAD. We excluded patients who had been diagnosed with CAD before TKR. CAD was defined as ICD-9-CM 410-414 coding in LHID 2005 which includes 410 acute myocardial infarction, 411 other acute and subacute forms of ischemic heart disease, 412 old myocardial infarction, 413 angina pectoris and 414 other forms of chronic ischemic heart disease. Finally, our study cohort included 1500 patients with TKR. Of the 1500 patients, 488 received GA and 1012 received SA–EA (676 cases of spinal anesthesia and 336 epidural blocks). Since our study used anonymous secondary data recorded and released from the LHID 2005, it was exempt from full review by an independent review board. The study baseline variable was CAD incidence before TKR based on whether a patient received GA or SA–EA. Patient characteristics were obtained for all subjects, including age, sex, operation procedure (unilateral vs. bilateral), and year of surgery. Also recorded was the age of the surgeon and comorbid diseases including hypertension (ICD-9-CM 401), diabetes (ICD-9-CM 250), or hyperlipidemia (ICD-9-CM 272). In this study, the Pearson Chi-square test was used to compare differences between the two cohorts. Time-toevent analysis (Kaplan–Meier method) was used to estimate CAD-free survival rate after the entry date, and the
123
log-rank test was also used to test differences in risk of CAD between patients who received GA and those who received SA–EA. We also used the Cox model to estimate the 90-day CAD-free survival rate and covered the following variables: age, gender, hypertension, hyperlipidemia, diabetes mellitus, cancer, year of surgery, surgical procedure and surgeon’s age. Because these variables wound affect an estimate CAD, we put them together into the model to get the corrected estimate of the hazard ratios (HR) for CAD among patients who received TKR in Taiwan during the 90-day post-surgical follow-up period. All statistical analyses were performed using the SAS statistical package (SAS System for Windows, Version 9.1.3, SAS Institute Inc., Cary, NC, USA). A two-tailed p value of \0.05 was considered statistically significant.
Results There is no significant difference between the gender, hyperlipidemia, diabetes mellitus, cancer, year of surgery, surgical procedure. The patients’ and the surgeons’ mean age are both elder in groups of SA–EA than that of GA (p \ 0.001). Patients who received SA–EA were more likely to have hypertension (p = 0.009) than those receiving GA (Table 1). The SA–EA/GA hazard ratio for CAD for the 90 days after surgery was 2.53 (95 % CI 1.06–6.07). After adjustment for the patient’s age, sex, hypertension, diabetes, cancer, hyperlipidemia, surgical procedure, the surgeon’s age and the year of surgery, this hazard ratio increased to 2.80 (95 % CI 1.16–6.78) (Table 2). The log-rank test in Kaplan–Meier survival curve in this study indicated that patients who received GA had significantly higher CAD-free survival rates than patients who received SA–EA (p = 0.032) (Fig. 1). After adjustment for the multiple coefficients of correlation of the patient’s age, sex, hypertension, diabetes, cancer, hyperlipidemia, surgical procedure, the surgeon’s age and the year of surgery in this study, the 1012 patients under SA– EA for TKR (group 1) and 488 patients under GA for TKR (group 2) were analyzed. The risk of developed CAD during the 90-day follow-up period was significantly higher in group 1 (3.1 %) than that in group 2 (1.2 %).
Discussion Numerous debates still occur about the actual incidence of post-operative deep venous thrombosis (DVT), pulmonary embolism, mortality, nausea, vomiting, pruritus, urinary retention, transfusion requirements, the duration of surgery, and length of hospital stay in patients receiving orthopedic surgery under SA–EA and GA [4–6]. Despite the
Eur J Orthop Surg Traumatol Table 1 Demographic characteristics of patients who received TKR under GA or SA– EA in Taiwan, 2004–2006 (n = 1500)
Baseline variable
General anesthesia (n = 488)
Epidural/spinal anesthesia (n = 1012)
Number
%
Number
%
p value
Patient characteristics Gender
0.497
Female
363
74.4
736
72.7
Male
125
25.6
276
27.3
82
16.8
99
9.8
\0.001
Age (years) B59 60–69
187
38.3
337
33.3
C70
219
44.9
576
56.9
255
52.3
601
59.4
233
47.7
411
40.6
Yes
98
20.1
214
31.4
No
390
79.9
798
68.6
Hypertension Yes No Diabetes
0.009
0.634
Cancer
0.692
Yes
20
4.1
46
4.5
No
468
95.9
966
95.5
Yes
106
21.7
241
23.8
No
382
78.3
771
76.2
Unilateral
63
12.9
140
13.8
Bilateral
425
87.1
872
86.2
Hyperlipidemia
0.368
Surgical procedure
0.624
Surgeon characteristics \0.001
Age (years) B40
102
20.9
166
16.4
41–50 C51
256 130
52.5 26.6
445 401
44.0 39.6
2004
156
32.0
365
36.1
2005
164
33.6
304
30.0
2006
168
34.4
343
33.9
Year of surgery
0.227
Table 2 Hazard ratios for IHD among patients who received TKR in Taiwan during the 90-day post-surgical follow-up period Variable
Total sample (n = 1500)
Epidural or spinal anesthesia (n = 1012)
General anesthesia (n = 488)
No.
%
No.
%
No.
%
Yes
37
2.5
31
3.1
6
1.2
No
1463
97.5
981
96.9
482
98.8
Crude HR (95 % CI)
–
–
2.53 (1.06–6.07)
1.00
Adjusted HR (95 % CI)a
–
–
2.80 (1.16–6.78)
1.00
90-day IHD
HR hazard ratio a
Adjustments made for patient’s age, gender, hypertension, hyperlipidemia, diabetes mellitus, cancer, year of surgery, surgical procedure and surgeon’s age
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Eur J Orthop Surg Traumatol
Fig. 1 Kaplan–Meier survival analysis of CAD—free survival rates during the 90-day post-operative period after TKR. Since our study used anonymous secondary data recorded and released from the LHID 2005, it was exempt from full review by an independent review board
controversies and some reports have claimed that SA–EA in TKR could decrease the prevalence of complications compared to GA, but there is still insufficient evidence to conclude whether anesthetic technique influenced cardiovascular morbidity in TKR [7–9]. In addition, many of these studies have been compromised by the relatively rare occurrence of complications or not focus on the cardiovascular events. It has to be disclosed that there is no significantly higher risk of CAD development among patients who received TKR under SA–EA than that under GA during the 120-day or longer post-surgical follow-up period. However, that is a debatable point, whether it is meaningful to investigate the relation between CAD and the different anesthesia for so long follow-up time. The incidence of CAD during or after SA–EA is quite low even it varies in different studies. In a large-scale 10-month prospective survey, the complication of CAD related to SA occurred in only nine cases in 35,439 SA procedures (2.5/10,000) [2]. The overall incidence of cardiac arrest was 1.5 per 10,000 anesthesia procedures (n = 11/71,816) for patients receiving regional anesthesia in a study of patients undergoing non-cardiac surgery [10]. The incidence of cardiac arrest with an incidence of 2.73 per 10,000 SA in a prospective multicenter study (n = 11/ 40,271) [11]. Incidence of CAD during or after operation under SA–EA is quite low even it varies in different studies; however, statistical tests to compare data cannot be
123
performed because the data are from different studies performed at different times with different surgeries. The incidence of CAD related to SA–EA in our study is higher than that reported in these previous studies. The etiology for possible pathophysiology with higher incidence of CAD following SA–EA in TKR is multifactorial. Theories regarding the mechanism by which neuraxial block contributes to cardiac arrest involve a circulatory etiology [1]. The perfusion pressure of coronary arteries is identical to ascending aortic diastolic pressure and is normally autoregulated [12]. Coronary autoregulatory mechanisms may fail to maintain adequate forward flow during extreme reductions in diastolic pressure, leading to perfusion defects and ischemia [13]. Concerning the reflex bradycardia seen in SA–EA, several pathophysiological mechanisms have been suggested to explain how bradycardia can be elicited from the decrease in preload caused by inhibition of sympathetic efferents during SA–EA [14–17]. In addition to these myocardial reflexes, SA–EA with a sympathetic blockade level of T1 or higher may alter the unopposed cardiac vagal input [18]. Bradycardia or hypotension with a close relationship to CAD is the most common cardiovascular disturbance associated with SA–EA and may result in impairment of coronary perfusion and in CAD [2, 3, 19]. In brief, SA–EA may contribute to cardiac events involve a circulatory etiology with the failed coronary autoregulatory mechanisms by reflex bradycardia. A procedure using a thigh tourniquet is almost always used during TKR surgery in order to minimize surgical bleeding and to keep the surgical field dry. Tourniquetinduced pain develops in patients undergoing surgery after tourniquet inflation and makes an increase in either systolic or diastolic arterial pressure [20]. The possible mechanism of the tourniquet-related hypertension in GA is that Nmethyl-D-aspartic acid (NMDA) receptor activation and central sensitization induced by repeated nociceptive C-fiber afferent input occur [21]. The unmyelinated and slow-conducting C-fibers that traverse the sympathetic trunk before entering the spinal cord above the level of the block cannot be blocked with regular doses of opiates or inhalational agents [22]. This may explain why the tourniquet-related hypertension is more common under GA (53–67 %) than SA (2.7–6.7 %) and occurs more often in lower-limb surgery than in upper-limb surgery [23, 24]. The major postoperative blood loss in unilateral TKR can amount to about 1000 ml [25]. In addition, decreased venous return and consequent decreased cardiac output, due to venous pooling in the lower extremity and vasodilation or myocardial depression caused by metabolites produced during the ischemic period, may contribute to a fall in arterial pressure after tourniquet deflation [26]. Therefore, hypotension due to hypovolemia from
Eur J Orthop Surg Traumatol
hemorrhage is commonly observed after tourniquet deflation and may be associated with occasional circulatory collapse [27, 28]. Hemodynamic changes may fluctuate in GA, with hypertension seen after tourniquet inflation and hypotension after tourniquet deflation. By contrast, the complete blockade of small diameter primary afferent fibers caused by SA may not prevent tourniquet-induced pain with a progressive increase in action potential discharge and a prolonged increase in the excitability of spinal cord neurons following tourniquet inflation [29]. Thus, the smooth blood pressure in SA during TKR surgery can be considered as a relatively prolonged hypotensive status after tourniquet inflation because of the lack of tourniquet-induced pain impulses, which may be a reason of circulation impairment after TKR with SA–EA especially. Relative hypotension due to no tourniquet-induced hypertension during tourniquet inflation and major postoperative blood loss after tourniquet deflation make prolonged circulatory impairment following TKR with SA–EA. The hemodynamic fluctuation may impact on patients following TKR under SA–EA with a higher risk of CAD. The findings of this study need to be interpreted in the context of the following limitations. First, statistical tests to compare data cannot be performed because the data are from different studies performed at different times with different surgeries. Second, diagnoses of CAD or any other comorbid medical condition that are completely dependent on the International Classification of Diseases codes may be less accurate than those obtained through a standardized examinations. Third, because IHD cases were detected by orthopedic surgeons or other physicians, it is difficult to recognize whether all doctors diagnosed using identical criteria for confirmation of CAD inclusive of the ICD-9CM codes 410-414. Fourth, because a claim database was used, study data were not available to investigate some risk factors such as increased body mass index, cigarette smoking, race, dietary habits, and physical exercise in the regression model, and these risk factors might contribute to CAD development and potentially affect the findings. In summary, patients who underwent TKR under SA– EA had an increased risk for CAD compared to those given GA during this procedure during the 90-day follow-up after adjustment for the multiple coefficients of correlation. The purpose of this study is not to suggest abandonment of the practice of SA–EA for TKR, but the anesthesiologists or orthopedic surgeons should not ignore the phenomenon. However, a larger series is required to confirm the conclusion of this article. Acknowledgments We thank the Taiwan National Health Research Institutes for their institutional support.
Conflict of interest There is no conflict of interests in connection with this article and submission.
References 1. Agarwal A, Kishore K (2009) Complications and controversies of regional anaesthesia: a review. Indian J Anaesth 53:543–553 2. Auroy Y, Benhamou D, Bargues L, Ecoffey C, Falissard B, Mercier FJ, Bouaziz H, Samii K (2002) Major complications of regional anesthesia in France: the SOS Regional Anesthesia Hotline Service. Anesthesiology 97:1274–1280 3. Faccenda KA, Finucane BT (2001) Complications of regional anaesthesia Incidence and prevention. Drug Saf 24:413–442 4. Chu CP, Yap JC, Chen PP, Hung HH (2006) Postoperative outcome in Chinese patients having primary total knee arthroplasty under general anaesthesia/intravenous patient-controlled analgesia compared to spinal epidural anaesthesia/analgesia. Hong Kong Med J 12:442–447 5. Williams-Russo P, Sharrock NE, Haas SB, Insall J, Windsor RE, Laskin RS, Ranawat CS, Go G, Ganz SB (1996) Randomized trial of epidural versus general anesthesia: outcomes after primary total knee replacement. Clin Orthop Relat Res 331:199–208 6. Macfarlane AJR, Prasad GA, Chan VWS, Brull R (2009) Does regional anaesthesia improve outcome after total hip arthroplasty? A systematic review. Br J Anaesth 103:335–345 7. Hu S, Zhang ZY, Hua YQ, Li J, Cai ZD (2009) A comparison of regional and general anaesthesia for total replacement of the hip or knee: a meta-analysis. J Bone Joint Surg Br 91(B):935–942 8. Mauermann WJ, Shilling AM, Zuo Z (2006) A comparison of neuraxial block versus general anesthesia for elective total hip replacement: a meta-analysis. Anesth Analg 103:1018–1025 9. Dorr LD (2010) Regional anesthesia improves perioperative events in patients having total hip or knee replacement. J Bone Joint Surg Am 92:1264 10. Sprung J, Warner ME, Contreras MG, Schroeder DR, Beighley CM, Wilson GA, Warner DO (2003) Predictors of survival following cardiac arrest in patients undergoing noncardiac surgery: a study of 518,294 patients at a tertiary referral center. Anesthesiology 99:259–269 11. Charuluxananan S, Thienthong S, Rungreungvanich M, Chanchayanon T, Chinachoti T, Kyokong O, Punjasawadwong Y (2008) Cardiac arrest after spinal anesthesia in Thailand: a prospective multicenter registry of 40,271 anesthetics. Anesth Analg 107:1735–1741 12. Cruickshank JM (1992) The role of coronary perfusion pressure. Eur Heart J 13:39–43 13. Owens P, O’Brien E (1999) Hypotension in patients with coronary disease: Can profound hypotensive events cause myocardial ischaemic events? Heart 82:477–481 14. Liguori GA, Sharrock NE (1997) Asystole and severe bradycardia during epidural anesthesia in orthopedic patients. Anesthesiology 86:250–257 15. Dickinson CJ (1993) Fainting precipitated by collapse-firing of venous baroreceptors. Lancet 342:970–972 16. Pathak CL (1973) Autoregulation of chronotropic response of the heart through pacemaker stretch. Cardiology 58:45–64 17. Kinsella SM, Tuckey JP (2001) Perioperative bradycardia and asystole: relationship to vasovagal syncope and the Bezold–Jarisch reflex. Br J Anaesth 86:859–868 18. Mackey DC, Carpenter RL, Thompson GE, Brown DL, Bodily MN (1989) Bradycardia and asystole during spinal anesthesia: a report of three cases without morbidity. Anesthesiology 70:866–868
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thigh tourniquet in orthopaedic patients. Acta Anaesthesiol Scand 29:142–147 Berman AT, Geissele AE, Bosacco SJ (1988) Blood loss with total knee arthroplasty. Clin Orthop Relat Res 234:137–138 Lotke PA, Faralli VJ, Orenstein EM, Ecker ML (1991) Blood loss after total knee replacement. Effects of tourniquet release and continuous passive motion. J Bone Joint Surg Am 73:1037–1040 Benzon HT, Toleikis JR, Meagher LL, Shapiro BA, Ts’ao CH, Avram MJ (1988) Changes in venous blood lactate, venous blood gases, and somatosensory evoked potentials after tourniquet application. Anesthesiology 69:677–682 Kahn RL, Marino V, Urquhart B, Sharrock NE (1992) Hemodynamic changes associated with tourniquet use under epidural anesthesia for total knee arthroplasty. Reg Anesth 17:228–232 Woolf CJ, Thompson SW (1991) The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain 44:293–299
ORIGINAL ARTICLE • KNEE - ANESTHESIA
Less incidence of coronary artery disease in general anesthesia compared to spinal–epidural anesthesia after total knee replacement: 90-day follow-up period by a population-based dataset Jui-Yang Hsieh1 • Hui-Wen Lin2
Received: 29 September 2014 / Accepted: 24 February 2015 Springer-Verlag France 2015
Abstract Total knee replacement (TKR) is an effective and safe procedure. However, large-scale study to compare the incidence of coronary artery disease (CAD) after spinal or epidural anesthesia (SA–EA) or general anesthesia (GA) for TKR has not ever been conducted. To do so, we studied a population-based dataset from the Taiwan National Health Research Institute and hypothesized that the incidence of CAD might be different with regional than with general anesthesia. The risk of CAD-related events during a 90-day follow-up period among patients who received TKR under SA–EA or GA was evaluated in the present study. A total of 1500 patients from the Taiwan National Health Insurance claims database who underwent TKR from January 1, 2004, to December 31, 2006, were allocated into two groups. Group 1 included 1012 patients who received SA–EA during TKR procedure. Group 2 included 488 patients who received GA during this procedure. The number of patients who developed CAD during the 90-day follow-up period was 31 (3.1 %) in group 1 and 6 (1.2 %) in group 2. The Kaplan–Meier survival analysis of IHDfree cumulative survival rate during the 90-day follow-up period for patients who underwent TKR was significantly lower in group 1 than in group 2. The hazard ratio for the occurrence of CAD was 2.80 (95 % CI 1.16–6.78), and the
& Jui-Yang Hsieh [email protected] Hui-Wen Lin [email protected] 1
Department of Orthopedics, National Taiwan University Hospital and Jinshan Branch, No. 7, Chung-Shan South Road, Taipei 100, Taiwan, ROC
2
Department of Mathematics, Soochow University, 70 Linshi Road, Shihlin, Taipei 111, Taiwan, ROC
hazard was higher for patients who received SA–EA than for patients who received GA after adjusted potential confounding factors. After the performance of TKR, patients had a potentially increased risk for CAD in SA–EA compared to GA during the 90-day follow-up period. Keywords Coronary artery disease General anesthesia Spinal–epidural anesthesia Total knee replacement
Introduction Primary total knee replacement (TKR) is an effective and safe procedure commonly performed for knee joint failure caused by osteoarthritis, rheumatoid arthritis and other types of inflammatory arthritis. Regional anesthesia of spinal or epidural anesthesia (SA–EA) and general anesthesia (GA) are prevalent methods used for such surgery. SA–EA provides excellent anesthesia for many surgical procedures and is associated with multiple benefits compared to GA when used for orthopedic surgery. But like all powerful techniques, a number of complications of SA–EA have long been recognized, including post dural puncture headache (PDPH), backache, transient neurological symptoms, total spinal anesthesia, spinal or epidural hematoma, epidural abscess, meningitis, intracranial bleeding, cauda equina syndrome, arachnoiditis, cardiac arrest, urinary retention and drug toxicity [1–3]. However, large-scale study to compare the incidence of coronary artery disease (CAD) after SA–EA or GA for TKR has not ever been conducted. The aim of the present study was to evaluate the risk of future CAD development among patients who received TKR under SA–EA or GA during the 90-day post-surgical follow-up period. To do so, we hypothesized that the incidence of CAD might be
123
Eur J Orthop Surg Traumatol
different in regional and GA by using a population-based dataset from the Taiwan National Health Research Institute.
Materials and methods The National Health Insurance program has been implemented in Taiwan since 1995, and covers all medical benefit claims of ambulatory care, offers complete freedom of choice among healthcare providers and covers approximately 98 % of the total population of Taiwan. The Longitudinal Health Insurance Database 2005 (LHID 2005) released by the Taiwan National Health Research Institute in 2006 and the original claims data for reimbursement for one million enrollees under the National Health Insurance program were used as a data source. This cohort study was conducted using the LHID 2005. We identified patients who had primary TKR from January 1, 2004, to December 31, 2006, based on the principal procedure code of 81.54 (TKR). Cohort entry was defined as the date when the patients received primary TKR from January 1, 2004, to December 31, 2006. If a patient received primary TKR twice during the 3 years, the latter one was excluded from the cohort study. All patients were followed for 90 days from the date of cohort entry or followed until they developed CAD. We excluded patients who had been diagnosed with CAD before TKR. CAD was defined as ICD-9-CM 410-414 coding in LHID 2005 which includes 410 acute myocardial infarction, 411 other acute and subacute forms of ischemic heart disease, 412 old myocardial infarction, 413 angina pectoris and 414 other forms of chronic ischemic heart disease. Finally, our study cohort included 1500 patients with TKR. Of the 1500 patients, 488 received GA and 1012 received SA–EA (676 cases of spinal anesthesia and 336 epidural blocks). Since our study used anonymous secondary data recorded and released from the LHID 2005, it was exempt from full review by an independent review board. The study baseline variable was CAD incidence before TKR based on whether a patient received GA or SA–EA. Patient characteristics were obtained for all subjects, including age, sex, operation procedure (unilateral vs. bilateral), and year of surgery. Also recorded was the age of the surgeon and comorbid diseases including hypertension (ICD-9-CM 401), diabetes (ICD-9-CM 250), or hyperlipidemia (ICD-9-CM 272). In this study, the Pearson Chi-square test was used to compare differences between the two cohorts. Time-toevent analysis (Kaplan–Meier method) was used to estimate CAD-free survival rate after the entry date, and the
123
log-rank test was also used to test differences in risk of CAD between patients who received GA and those who received SA–EA. We also used the Cox model to estimate the 90-day CAD-free survival rate and covered the following variables: age, gender, hypertension, hyperlipidemia, diabetes mellitus, cancer, year of surgery, surgical procedure and surgeon’s age. Because these variables wound affect an estimate CAD, we put them together into the model to get the corrected estimate of the hazard ratios (HR) for CAD among patients who received TKR in Taiwan during the 90-day post-surgical follow-up period. All statistical analyses were performed using the SAS statistical package (SAS System for Windows, Version 9.1.3, SAS Institute Inc., Cary, NC, USA). A two-tailed p value of \0.05 was considered statistically significant.
Results There is no significant difference between the gender, hyperlipidemia, diabetes mellitus, cancer, year of surgery, surgical procedure. The patients’ and the surgeons’ mean age are both elder in groups of SA–EA than that of GA (p \ 0.001). Patients who received SA–EA were more likely to have hypertension (p = 0.009) than those receiving GA (Table 1). The SA–EA/GA hazard ratio for CAD for the 90 days after surgery was 2.53 (95 % CI 1.06–6.07). After adjustment for the patient’s age, sex, hypertension, diabetes, cancer, hyperlipidemia, surgical procedure, the surgeon’s age and the year of surgery, this hazard ratio increased to 2.80 (95 % CI 1.16–6.78) (Table 2). The log-rank test in Kaplan–Meier survival curve in this study indicated that patients who received GA had significantly higher CAD-free survival rates than patients who received SA–EA (p = 0.032) (Fig. 1). After adjustment for the multiple coefficients of correlation of the patient’s age, sex, hypertension, diabetes, cancer, hyperlipidemia, surgical procedure, the surgeon’s age and the year of surgery in this study, the 1012 patients under SA– EA for TKR (group 1) and 488 patients under GA for TKR (group 2) were analyzed. The risk of developed CAD during the 90-day follow-up period was significantly higher in group 1 (3.1 %) than that in group 2 (1.2 %).
Discussion Numerous debates still occur about the actual incidence of post-operative deep venous thrombosis (DVT), pulmonary embolism, mortality, nausea, vomiting, pruritus, urinary retention, transfusion requirements, the duration of surgery, and length of hospital stay in patients receiving orthopedic surgery under SA–EA and GA [4–6]. Despite the
Eur J Orthop Surg Traumatol Table 1 Demographic characteristics of patients who received TKR under GA or SA– EA in Taiwan, 2004–2006 (n = 1500)
Baseline variable
General anesthesia (n = 488)
Epidural/spinal anesthesia (n = 1012)
Number
%
Number
%
p value
Patient characteristics Gender
0.497
Female
363
74.4
736
72.7
Male
125
25.6
276
27.3
82
16.8
99
9.8
\0.001
Age (years) B59 60–69
187
38.3
337
33.3
C70
219
44.9
576
56.9
255
52.3
601
59.4
233
47.7
411
40.6
Yes
98
20.1
214
31.4
No
390
79.9
798
68.6
Hypertension Yes No Diabetes
0.009
0.634
Cancer
0.692
Yes
20
4.1
46
4.5
No
468
95.9
966
95.5
Yes
106
21.7
241
23.8
No
382
78.3
771
76.2
Unilateral
63
12.9
140
13.8
Bilateral
425
87.1
872
86.2
Hyperlipidemia
0.368
Surgical procedure
0.624
Surgeon characteristics \0.001
Age (years) B40
102
20.9
166
16.4
41–50 C51
256 130
52.5 26.6
445 401
44.0 39.6
2004
156
32.0
365
36.1
2005
164
33.6
304
30.0
2006
168
34.4
343
33.9
Year of surgery
0.227
Table 2 Hazard ratios for IHD among patients who received TKR in Taiwan during the 90-day post-surgical follow-up period Variable
Total sample (n = 1500)
Epidural or spinal anesthesia (n = 1012)
General anesthesia (n = 488)
No.
%
No.
%
No.
%
Yes
37
2.5
31
3.1
6
1.2
No
1463
97.5
981
96.9
482
98.8
Crude HR (95 % CI)
–
–
2.53 (1.06–6.07)
1.00
Adjusted HR (95 % CI)a
–
–
2.80 (1.16–6.78)
1.00
90-day IHD
HR hazard ratio a
Adjustments made for patient’s age, gender, hypertension, hyperlipidemia, diabetes mellitus, cancer, year of surgery, surgical procedure and surgeon’s age
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Fig. 1 Kaplan–Meier survival analysis of CAD—free survival rates during the 90-day post-operative period after TKR. Since our study used anonymous secondary data recorded and released from the LHID 2005, it was exempt from full review by an independent review board
controversies and some reports have claimed that SA–EA in TKR could decrease the prevalence of complications compared to GA, but there is still insufficient evidence to conclude whether anesthetic technique influenced cardiovascular morbidity in TKR [7–9]. In addition, many of these studies have been compromised by the relatively rare occurrence of complications or not focus on the cardiovascular events. It has to be disclosed that there is no significantly higher risk of CAD development among patients who received TKR under SA–EA than that under GA during the 120-day or longer post-surgical follow-up period. However, that is a debatable point, whether it is meaningful to investigate the relation between CAD and the different anesthesia for so long follow-up time. The incidence of CAD during or after SA–EA is quite low even it varies in different studies. In a large-scale 10-month prospective survey, the complication of CAD related to SA occurred in only nine cases in 35,439 SA procedures (2.5/10,000) [2]. The overall incidence of cardiac arrest was 1.5 per 10,000 anesthesia procedures (n = 11/71,816) for patients receiving regional anesthesia in a study of patients undergoing non-cardiac surgery [10]. The incidence of cardiac arrest with an incidence of 2.73 per 10,000 SA in a prospective multicenter study (n = 11/ 40,271) [11]. Incidence of CAD during or after operation under SA–EA is quite low even it varies in different studies; however, statistical tests to compare data cannot be
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performed because the data are from different studies performed at different times with different surgeries. The incidence of CAD related to SA–EA in our study is higher than that reported in these previous studies. The etiology for possible pathophysiology with higher incidence of CAD following SA–EA in TKR is multifactorial. Theories regarding the mechanism by which neuraxial block contributes to cardiac arrest involve a circulatory etiology [1]. The perfusion pressure of coronary arteries is identical to ascending aortic diastolic pressure and is normally autoregulated [12]. Coronary autoregulatory mechanisms may fail to maintain adequate forward flow during extreme reductions in diastolic pressure, leading to perfusion defects and ischemia [13]. Concerning the reflex bradycardia seen in SA–EA, several pathophysiological mechanisms have been suggested to explain how bradycardia can be elicited from the decrease in preload caused by inhibition of sympathetic efferents during SA–EA [14–17]. In addition to these myocardial reflexes, SA–EA with a sympathetic blockade level of T1 or higher may alter the unopposed cardiac vagal input [18]. Bradycardia or hypotension with a close relationship to CAD is the most common cardiovascular disturbance associated with SA–EA and may result in impairment of coronary perfusion and in CAD [2, 3, 19]. In brief, SA–EA may contribute to cardiac events involve a circulatory etiology with the failed coronary autoregulatory mechanisms by reflex bradycardia. A procedure using a thigh tourniquet is almost always used during TKR surgery in order to minimize surgical bleeding and to keep the surgical field dry. Tourniquetinduced pain develops in patients undergoing surgery after tourniquet inflation and makes an increase in either systolic or diastolic arterial pressure [20]. The possible mechanism of the tourniquet-related hypertension in GA is that Nmethyl-D-aspartic acid (NMDA) receptor activation and central sensitization induced by repeated nociceptive C-fiber afferent input occur [21]. The unmyelinated and slow-conducting C-fibers that traverse the sympathetic trunk before entering the spinal cord above the level of the block cannot be blocked with regular doses of opiates or inhalational agents [22]. This may explain why the tourniquet-related hypertension is more common under GA (53–67 %) than SA (2.7–6.7 %) and occurs more often in lower-limb surgery than in upper-limb surgery [23, 24]. The major postoperative blood loss in unilateral TKR can amount to about 1000 ml [25]. In addition, decreased venous return and consequent decreased cardiac output, due to venous pooling in the lower extremity and vasodilation or myocardial depression caused by metabolites produced during the ischemic period, may contribute to a fall in arterial pressure after tourniquet deflation [26]. Therefore, hypotension due to hypovolemia from
Eur J Orthop Surg Traumatol
hemorrhage is commonly observed after tourniquet deflation and may be associated with occasional circulatory collapse [27, 28]. Hemodynamic changes may fluctuate in GA, with hypertension seen after tourniquet inflation and hypotension after tourniquet deflation. By contrast, the complete blockade of small diameter primary afferent fibers caused by SA may not prevent tourniquet-induced pain with a progressive increase in action potential discharge and a prolonged increase in the excitability of spinal cord neurons following tourniquet inflation [29]. Thus, the smooth blood pressure in SA during TKR surgery can be considered as a relatively prolonged hypotensive status after tourniquet inflation because of the lack of tourniquet-induced pain impulses, which may be a reason of circulation impairment after TKR with SA–EA especially. Relative hypotension due to no tourniquet-induced hypertension during tourniquet inflation and major postoperative blood loss after tourniquet deflation make prolonged circulatory impairment following TKR with SA–EA. The hemodynamic fluctuation may impact on patients following TKR under SA–EA with a higher risk of CAD. The findings of this study need to be interpreted in the context of the following limitations. First, statistical tests to compare data cannot be performed because the data are from different studies performed at different times with different surgeries. Second, diagnoses of CAD or any other comorbid medical condition that are completely dependent on the International Classification of Diseases codes may be less accurate than those obtained through a standardized examinations. Third, because IHD cases were detected by orthopedic surgeons or other physicians, it is difficult to recognize whether all doctors diagnosed using identical criteria for confirmation of CAD inclusive of the ICD-9CM codes 410-414. Fourth, because a claim database was used, study data were not available to investigate some risk factors such as increased body mass index, cigarette smoking, race, dietary habits, and physical exercise in the regression model, and these risk factors might contribute to CAD development and potentially affect the findings. In summary, patients who underwent TKR under SA– EA had an increased risk for CAD compared to those given GA during this procedure during the 90-day follow-up after adjustment for the multiple coefficients of correlation. The purpose of this study is not to suggest abandonment of the practice of SA–EA for TKR, but the anesthesiologists or orthopedic surgeons should not ignore the phenomenon. However, a larger series is required to confirm the conclusion of this article. Acknowledgments We thank the Taiwan National Health Research Institutes for their institutional support.
Conflict of interest There is no conflict of interests in connection with this article and submission.
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