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Influence of Dexmedetomidine on the Tourniquet Related Responses in Hypertension Patients Receiving Unilateral Knee Arthroplasty under General Anesthesia
The Journal of Arthroplasty xxx (2015) xxx–xxx
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The Journal of Arthroplasty journal homepage: www.arthroplastyjournal.org
Influence of Dexmedetomidine on the Tourniquet Related Responses in Hypertension Patients Receiving Unilateral Knee Arthroplasty under General Anesthesia Yong-Hua Y. Li, MD a,1, Yong-Qiang Y. Wang, MD b,1, Yi-Jie Y. Zhang, MD c,1, Dong-Yu D. Zheng, MD a, Liu Hu H., MD a, Mou-Li M. Tian, MD a a b c
Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, China Department of Anesthesiology, Shuguang Hospital, Traditional Chinese Medicine University, Shanghai, China Department of Anesthesiology, Qilu Hospital of Tsingdao City, Tsingdao, Shandong, China
a r t i c l e
i n f o
Article history: Received 6 November 2014 Accepted 24 February 2015 Available online xxxx Keywords: dexmedetomidine unilateral knee arthroplasty hemodynamic lung function hypertension
a b s t r a c t This study aimed to investigate the influence of dexmedetomidine (DEX) on the tourniquet related responses in hypertension patients receiving unilateral knee arthroplasty (UKA) under general anesthesia. Results showed that the incidence of tourniquet induced hypertension (TIH), hemodynamics, MAC and EtSEV in DEX group were significantly lower than those in control group, regardless of hypertension. However, significant differences in TIH, hemodynamics, minimum alveolar concentration (MAC) and end-tidal sevoflurane (EtSEV) were not observed between hypertension patients and non-hypertension patients in both control group and DEX group. Moreover, oxygen index (OI) and respiratory index (RI) remained unchanged after deflation and DEX failed to affect OI and RI within 30 min after deflation, regardless of hypertension. Taken together, DEX may significantly improve the hemodynamics, which is independent of pre-existing hypertension. © 2015 Elsevier Inc. All rights reserved.
Surgery of the extremities is frequently performed after exsanguination of the limb followed by inflation of a tourniquet, aiming to obtain bloodless operating conditions and to prevent unnecessary blood loss. However, prolonged tourniquet inflation may cause a gradual rise in blood pressure, which is also known as tourniquet induced hypertension (TIH). TIH occurs more frequently in patients receiving general anesthesia and/or lower limb surgery [1]. There is no consensus on the definition of TIH. In previous studies, TIH was defined as a rise of more than 30% in systolic or diastolic blood pressure [2,3]. According to this definition, the incidence of TIH in general anesthesia varies among studies and patients receiving different types of anesthesia. Kaufman and Walts reported that the frequency of TIH was 11% in a group of 500 patients whose operations involved the use of a tourniquet in lower limbs surgery [2]. In a retrospective study on 699 patients receiving orthopedic surgery using prolonged tourniquet inflation with a minimum of one hour of anesthesia, hypertension was found in 67% of patients receiving general anesthesia, 18.6% of the patients receiving intravenous regional anesthesia (IVRA), 2.7% of the patients operated under spinal anesthesia and 2.5% of the patients receiving a brachial plexus anesthetic [4]. 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 http://dx.doi.org/10.1016/j.arth.2015.02.034 Reprint requests: Mou-Li Tian, MD, and Liu Hu, MD, Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, Huangpu District, 200003, Shanghai, China. 1 All contribute to this work equally.
TIH during the surgery may increase the risk for cardiovascular events (such as coronary ischemia and arrhythmia), especially in patients with advanced age, concomitant hypertension, ischemic heart disease and atherosclerosis [5]. Moreover, tourniquet inflation–deflation induced ischemia and reperfusion may cause damage to the lung, leading to the impairment to the gas exchange of the lung [6]. Thus, to deeply investigate the tourniquet related hemodynamic responses and ischemia–reperfusion injury is important for patients receiving limb surgery under general anesthesia. Dexmedetomidine (DEX), an imidazole compound, is the pharmacologically active dextroisomer of medetomidine [7], which displays specific and selective α2-adrenoceptor agonism. Since its release in the US market in late 1999, it has gained remarkable attention in the adult, pediatric and geriatric populations, predominantly because of its minimal respiratory depression. Besides the sedative, analgesic and anxiolytic properties [8], studies in recent years also reveal that DEX has its potential in many other clinical scenarios, including neuroprotection, cardioprotection and renoprotection, with promising results [9]. Theoretically, DEX may exert significant effects on attenuating tourniquet-induced hyperdynamic responses including TIH, which has been confirmed in several studies [10,11]. In addition, pre-operative use of DEX is also helpful to reduce the dose of anesthetics [12]. However, in hypertension patients, the impact of DEX is still unclear because hypertension patients were usually excluded from some studies [10,11]. In the present study, patients with or without hypertension receiving elective unilateral knee arthroplasty (UKA) were recruited to investigate
http://dx.doi.org/10.1016/j.arth.2015.02.034 0883-5403/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Li Y-HY, et al, Influence of Dexmedetomidine on the Tourniquet Related Responses in Hypertension Patients Receiving Unilateral Knee Arthroplasty under General Anesthesia, J Arthroplasty (2015), http://dx.doi.org/10.1016/j.arth.2015.02.034
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Y-H.Y. Li et al. / The Journal of Arthroplasty xxx (2015) xxx–xxx
Table 1 Demographic Data in Control Group and DEX Group.
Table 3 Incidence of TIH in Different Groups (n, %).
Variable
Control Group (n = 39) DEX Group (n = 41)
Group
Control
DEX
Total
Age (years) Height (cm) Body weight (kg) BMI (kg/cm2) Gender (M/F) Tourniquet time (min) History of hypertension (yes/no)
66.1 ± 7.5 160.3 ± 6.9 65.2 ± 10.2 25.3 ± 3.4 10/29 76.3 ± 13.8 18/21
Non-hypertension Hypertension Total
14 (66.7%) 14 (77.8%) 28 (71.8%)
2 (12.5%) 12 (48.0%) 14 (34.1%)
16 (43.2%) 26 (60.5%)
65.0 ± 7.9 159.7 ± 6.6 67.7 ± 11.0 26.4 ± 3.5 9/32 79.7 ± 11.3 25/16
whether hypertension may influence the hemodynamics and inhaled anesthesia related parameters following pre-operative use of DEX. Materials and methods
Following anesthesia induction, DEX at a loading dose of 1 μg/kg was injected via a pump within 20 min, and maintenance was done with DEX at 0.4 μg/kg/h until tourniquet deflation. In control group, normal saline of equal volume was injected. Adequate muscle relaxation was maintained during surgery to avoid the changes in BP and HR. TIH was defined as invasive SBP higher than 160 mmHg for at least 1 min at 20 min after tourniquet inflation. In addition, the rate pressure product (RPP) was also calculated.
Inclusion of patients A total of 80 patients (ASA grade I-III) receiving elective unilateral knee arthroplasty were recruited from the Department of Joint Surgery from July 2011 to January 2012. The mean age was 65.4 ± 7.8 years (range: 46–75 years). There were 19 males and 61 females. In addition, 43 patients had a history of doctor diagnosed hypertension. Hypertension was diagnosed according to the Guideline for the Prevention and Treatment of Hypertension in China [13]. Exclusion criteria: (1) Patients were allergic to DEX or other drugs used in the present study; (2) patients had respiratory infections recently, chronic cough, asthma and chronic obstructive lung disease; (3) patients had severe liver and/or kidney dysfunction; (4) patients had severe sinus bradycardia (b50 beats/min); (5) patients had type II second-degree atrioventricular block. This study was registered in Chinese Clinical Trial Register (ChiCTRTRC-11001714) and informed consent was obtained from each patient before study. The whole protocol was approved by the Ethics Committee of Chinese Clinical Trial Register (ChiECRCT-2011044). Treatments Patients were randomly divided into control group and DEX group. All the patients received food and water deprivation for 8 h before surgery. Before anesthesia, an access to the upper limb vein was prepared for the fluid infusion and detection of bispectral index (BIS). The heart rate (HR) was routinely monitored and the blood pressure (BP; systolic blood pressure, SBP) was measured invasively via the left radial artery. End-tidal concentration of sevoflurane (EtSEV) and minimal alveolar concentration (MAC) were recorded during anesthesia. Before anesthesia induction, Ringer's acetate was infused at 5 ml/kg. For anesthesia induction, midazolam at 0.05 mg/kg, propofol at 1 mg/kg, fentanyl at 3 μg/kg and cis-atracurium at 0.3 mg/kg were injected, followed by tracheal intubation and subsequent mechanical ventilation via an anesthesia machine when the BIS reduced to lower than 60. The tidal volume was 10 ml/kg and respiratory rate was 12 breaths/min. Anesthesia was maintained with sevoflurane, and all patients' lungs were mechanically ventilated with 1 L/min fresh gas. The anesthesia depth was adjusted to maintain the BIS at 40–60. The liquid crystal was infused at 6 ml/kg/h via a micropump during surgery. Table 2 Demographics of Hypertension Patients and Non-Hypertension Patients. Variable
Hypertension (n = 43)
Non-Hypertension (n = 37)
Age (years) Height (cm) Body weight (kg) BMI (kg/cm2) Gender (M/F) Tourniquet time (min)
66.0 ± 6.8 160.4 ± 6.4 69.2 ± 11.6 26.7 ± 3.4 11/32 78.7 ± 12.8
64.8 ± 8.8 159.7 ± 7.4 68.1 ± 9.0 26.9 ± 3.3 8/29 77.2 ± 12.9
Application of tourniquet ZJ-1 numerical control pneumatic tourniquet (width: 71 mm) was used. Following anesthesia, the tourniquet was wrapped at the root of thigh. Mechanical limb exsanguination was performed with an elastic bandage prior to commencing surgery, followed by inflation.
Observations Demographics including age, gender, height and body weight as well as the history of doctor diagnosed hypertension were recorded. The hemodynamic parameters (HR, SBP, mean arterial pressure [MAP], cardiac index [CI], stroke volume index [SVI] and systemic vascular resistance index [SVRI]) were detected or calculated before anesthesia induction (T0) and at different time points (0 [T1], 20 [T2], 30 [T3], 40 [T4], 50 [T5] and 60 min [T6]) after inflation. In addition, the EtSEV and MAC of sevoflurane were also recorded. One minute before and within 30 min after deflation (5, 15 and 30 min), the arterial partial pressure of oxygen (PaO2), fraction of inspired oxygen (FiO2) and alveolo-arterial oxygen partial pressure difference (P(A-a)O2) were measured, followed by calculation of oxygenation index (OI) and respiratory index (RI).
Statistical analysis Quantitative data are expressed as mean ± standard deviation (SD). Comparisons were done with repeated-measures analysis of variance of variance for data collected at different time points and with analysis of variance for those in a specific group. Qualitative data were compared with chi square test. Statistical analysis was performed with SPSS version 18.0, and a value of P b 0.05 was considered statistically significant.
Results General information There were no marked differences in the gender, age, body weight, height, BMI, tourniquet time and history of hypertension between control group and DEX group (P N 0.05; Table 1), and hypertension patients and non-hypertension also matched in the gender, age, body weight, height, BMI and tourniquet time (P N 0.05; Table 2). There were no marked differences in the use of Ringer's acetate and liquid crystal. Loading dose (1 μg/kg) of DEX was injected via a pump for 20 min, and no patients had the heart rate of b 45 bpm. Patients were closely monitored, and there were no complications related to hypertension.
Please cite this article as: Li Y-HY, et al, Influence of Dexmedetomidine on the Tourniquet Related Responses in Hypertension Patients Receiving Unilateral Knee Arthroplasty under General Anesthesia, J Arthroplasty (2015), http://dx.doi.org/10.1016/j.arth.2015.02.034
Y-H.Y. Li et al. / The Journal of Arthroplasty xxx (2015) xxx–xxx
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Table 4 Hemodynamic Parameters of Patients in Control Group (x ± s). Variables
Group
T0
T1
T2
T3
T4
T5
T6
HR (bpm)
Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P
71.8 ± 8.0 74.9 ± 11.1 0.323 157.1 ± 16.2 165.7 ± 18.9 0.133 105.0 ± 11.2 108.6 ± 11.4 0.326 11,259 ± 1586 12,336 ± 2294 0.093 3.30 ± 0.78 3.18 ± 0.75 0.612 46.4 ± 10.9 44.4 ± 10.2 0.563 2690 ± 693 2700 ± 476 0.960
59.4 ± 9.7 58.0 ± 8.0 0.622 116.0 ± 19.2 117.2 ± 25.0 0.864 82.7 ± 15.9 81.2 ± 18.3 0.786 6999 ± 2339 6885 ± 2120 0.842 2.48 ± 0.59 2.43 ± 0.58 0.818 42.0 ± 9.0 42.6 ± 9.0 0.864 2587 ± 503 2635 ± 342 0.746
67.0 ± 9.2 65.0 ± 11.7 0.565 153.4 ± 22.1 155.5 ± 21.9 0.771 109.6 ± 13.8 109.5 ± 17.0 0.988 10,284 ± 2111 10,258 ± 2509 0.964 2.90 ± 0.40 2.79 ± 0.49 0.473 44.3 ± 7.3 45.3 ± 9.0 0.703 2915 ± 512 2958 ± 551 0.810
67.6 ± 9.6 72.8 ± 20.8 0.311 152.4 ± 22.4 155.2 ± 28.2 0.732 109.0 ± 14.7 111.8 ± 14.9 0.553 10,331 ± 2265 11,145 ± 3082 0.973 3.00 ± 0.70 2.94 ± 0.60 0.777 44.9 ± 9.1 45.4 ± 10.5 0.885 2799 ± 604 2909 ± 585 0.582
65.7 ± 8.6 67.3 ± 13.1 0.646 149.2 ± 17.1 151.6 ± 19.8 0.691 106.6 ± 12.0 106.7 ± 14.5 0.981 9840 ± 1882 10,330 ± 2703 0.349 2.96 ± 0.46 2.85 ± 0.38 0.453 45.3 ± 6.7 44.3 ± 8.4 0.696 2787 ± 449 2849 ± 511 0.698
65.2 ± 10.5 68.4 ± 15.3 0.445 146.9 ± 20.4 149.4 ± 22.0 0.717 104.3 ± 15.1 105.8 ± 17.2 0.774 9687 ± 2574 10,356 ± 3504 0.511 3.02 ± 0.65 2.84 ± 0.45 0.365 46.4 ± 6.9 43.9 ± 9.0 0.356 2591 ± 734 2796 ± 468 0.337
64.7 ± 10.0 65.2 ± 10.7 0.879 142.0 ± 19.1 144.8 ± 20.4 0.651 102.2 ± 14.2 103.0 ± 12.8 0.854 9276 ± 2306 9481 ± 2130 0.504 3.04 ± 0.68 2.71 ± 0.44 0.103 47.2 ± 7.1 43.6 ± 9.8 0.195 2629 ± 459 2932 ± 601 0.091
SBP (mmHg) MAP (mmHg) RPP (bpm × mmHg) CI (L/min/m2) SVI (ml/b/m2) SVRI (kPa-s-m2/cmL)
Incidence of TIH BIS, EtSEV and MAC at different time points The incidence of TIH was 71.8% and 34.1% in control group and DEX group, respectively, showing marked difference (P b 0.01, Table 3). In control group, the incidence of TIH was 66.7% and 77.8% in nonhypertension patients and hypertension patients, respectively, suggesting no significant difference (P N 0.05). However, marked difference was observed in the incidence of TIH between non-hypertension patients and hypertension patients in DEX group (12.5% and 48.0%; P b 0.05).
In DEX patients, EtSEV at T4-T6 and MAC at T3-T6 were significantly lower than those in control patients in both hypertension and nonhypertension groups (P b 0.05). No marked differences in EtSEV at T2-T6 were observed between hypertension patients and non-hypertension patients in both control group and DEX group (P N 0.05) (Tables 6 and 7). In addition, BIS remained stable after anesthesia, and was comparable between control group and DEX group as well as between hypertension patients and non-hypertension patients (P N 0.05) (Tables 6 and 7).
Hemodynamic data at different time points The HR, SBP, RPP and CI at T2-T6 increased significantly in control group and DEX group when compared with those at T0 (P b 0.01). In addition, the HR, SBP, RPP and CI at T2-T6 in DEX patients reduced markedly when compared with control patients (P b 0.05 or b 0.01), in both hypertension and non-hypertension groups. However, the HR, SBP, RPP and CI at T2-T6 were comparable between hypertension patients and non-hypertension patients in both control group and DEX group (P N 0.05; Tables 4 and 5).
OI and RI after deflation The OI and RI remained unchanged after deflation. In addition, there were no significant differences in the OI and RI between control patients and DEX patients as well as between hypertension patients and nonhypertension patients (P N 0.05; Tables 8 and 9).
Table 5 Hemodynamic Parameters of Patients in DEX Group (x ± s). Variable
Group
T0
T1
T2
T3
T4
T5
T6
HR (bpm)
Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P
73.4 ± 12.7 76.1 ± 12.4 0.514 147.9 ± 17.3 176.9 ± 26.9 0.000 101.6 ± 13.9 114.3 ± 15.3 0.010 10,849 ± 2328 13,534 ± 3411 0.009 3.33 ± 0.75 3.44 ± 0.63 0.611 46.5 ± 7.9 47.5 ± 11.4 0.753 2391 ± 502 2773 ± 530 0.031⁎
54.8 ± 7.7 54.2 ± 7.4 0.814 130.8 ± 23.7 139.8 ± 29.9 0.314 93.2 ± 16.8 94.3 ± 20.9 0.861 7168 ± 8379 7569 ± 1965 0.517 2.61 ± 0.58 2.67 ± 0.89 0.813 47.6 ± 6.3 49.8 ± 13.9 0.572 2814 ± 511 2951 ± 508 0.418
59.8 ± 7.1 59.7 ± 10.3 0.992 139.7 ± 14.4 147.8 ± 23.3 0.218 102.7 ± 9.1 105.8 ± 15.6 0.469 8379 ± 1525 8901 ± 2415 0.445 2.69 ± 0.55 2.77 ± 0.64 0.674 43.1 ± 5.0 46.6 ± 7.8 0.124 3064 ± 484 3045 ± 522 0.910
60.1 ± 8.4 58.0 ± 6.5 0.392 137.0 ± 15.4 137.8 ± 22.5 0.906 100.4 ± 10.8 98.4 ± 15.6 0.654 8282 ± 1714 8007 ± 1630 0.609 2.73 ± 0.62 2.64 ± 0.59 0.632 43.2 ± 5.0 44.7 ± 7.8 0.505 2984 ± 570 3020 ± 444 0.830
60.3 ± 9.0 58.2 ± 8.6 0.455 137.8 ± 18.4 141.3 ± 23.5 0.615 101.7 ± 12.5 102.5 ± 16.2 0.869 8391 ± 2078 8294 ± 2206 0.890 2.74 ± 0.85 2.56 ± 0.46 0.375 43.4 ± 6.8 45.7 ± 9.2 0.403 3010 ± 584 3061 ± 552 0.786
57.8 ± 7.0 58.1 ± 8.2 0.915 133.0 ± 16.1 139.9 ± 25.4 0.340 97.1 ± 11.2 96.5 ± 18.4 0.916 7735 ± 1587 8211 ± 2348 0.481 2.63 ± 0.68 2.57 ± 0.55 0.782 43.2 ± 4.2 44.9 ± 9.1 0.491 2972 ± 507 2943 ± 475 0.858
56.9 ± 7.7 57.0 ± 8.9 0.975 124.5 ± 15.7 137.3 ± 26.1 0.085 93.3. ± 11.2 96.8 ± 19.9 0.520 7141 ± 1684 7873 ± 2222 0.267 2.69 ± 0.68 2.55 ± 0.42 0.435 46.9 ± 11.8 45.6 ± 7.0 0.675 2800 ± 395 2932 ± 523 0.400
SBP (mmHg) MAP (mmHg) RPP (bpm × mmHg) CI (L/min/m2) SVI (ml/b/m2) SVRI (kPa-s-m2/cmL)
Please cite this article as: Li Y-HY, et al, Influence of Dexmedetomidine on the Tourniquet Related Responses in Hypertension Patients Receiving Unilateral Knee Arthroplasty under General Anesthesia, J Arthroplasty (2015), http://dx.doi.org/10.1016/j.arth.2015.02.034
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Y-H.Y. Li et al. / The Journal of Arthroplasty xxx (2015) xxx–xxx
Table 6 BIS, EtSEV and MAC of Patients in Control Group (x ± s). Variable
Group
T0
T1
BIS
Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P
91.5 ± 4.2 91.2 ± 6.0 0.863
55.9 ± 54.5 ± 0.725 1.01 ± 1.16 ± 0.357 0.67 ± 0.78 ± 0.326
EtSEV (%) MAC
T2 10.0 10.3 0.47 0.49 0.30 0.34
44.9 ± 46.6 ± 0.643 1.64 ± 1.59 ± 0.435 1.06 ± 1.04 ± 0.851
Discussion Arterial tourniquets are used for extremity surgery to reduce blood loss and provide good operating conditions. However, prolong tourniquet inflation during general anesthesia causes increases in heart rate and blood pressure, which commonly lead the anesthetists to increase the depth of anesthesia. This clinical syndrome is commonly referred to as “tourniquet pain” [14]. DEX is a potent α2-adrenoceptor agonist with 8 times higher affinity for the α2-adrenoceptor than clonidine [9]. DEX has shown sedative, analgesic and anxiolytic effects in healthy volunteers or postsurgical patients in the intensive care unit [9]. Theoretically, DEX is able to attenuate the “tourniquet pain” according to its pathogenesis, which has been confirmed in previous studies [10,11,15]. However, hypertension was used as an exclusion criterion in previous studies [10,11], and thus patients with hypertension were often not recruited. In the present study, we investigated whether the pre-existing hypertension affects the protective effects of DEX on the “tourniquet pain”. Theoretically, the anti-hypertensive effect of DEX may continue for about 2 h (half-life). However, the tourniquet time was no longer than 90 min for patients receiving UKA in our hospital. So this study focused on the hemodynamics within 60 min after inflation. Our results showed that the incidence of TIH was 66.7% in non-hypertension patients of control group, which was consistent with a previous study [4]. In addition, pre-operative treatment with DEX was helpful to reduce the incidence of TIH, which was independent of hypertension. This suggests that hypertension has no influence on the protective effect of DEX on the TIH. In addition, in control group, the incidence of TIH was comparable between hypertension patients and non-hypertension patients, indicating that pre-existing hypertension is not associated with TIH. Of note, the reduction in the incidence of TIH was higher in nonhypertension patients than in hypertension patients following DEX therapy, indicating that hypertension has influence on the incidence of TIH after DEX. The HR, SBP, RPP and CI increased after tourniquet inflation. In addition, these parameters after tourniquet inflation in control group were significantly higher than those in DEX group, regardless of hypertension, suggesting that DEX is able to reduce hemodynamic parameters, which has been confirmed in previous studies [15–17]. However, there were no marked differences between hypertension and non-
T3 9.2 9.1 0.18 0.24 0.11 0.18
43.3 ± 48.0 ± 0.174 1.66 ± 1.57 ± 0.323 1.08 ± 1.06 ± 0.712
T4 8.7 8.9 0.20 0.27 0.12 0.17
45.5 ± 47.5 ± 0.450 1.66 ± 1.66 ± 0.919 1.07 ± 1.09 ± 0.733
T5 6.7 7.0 0.21 0.27 0.16 0.18
45.9 ± 45.1 ± 0.742 1.66 ± 1.64 ± 0.798 1.07 ± 1.07 ± 0.989
T6 6.9 6.4 0.17 0.26 0.13 0.19
43.9 ± 46.3 ± 0.390 1.59 ± 1.66 ± 0.445 1.04 ± 1.10 ± 0.382
6.8 7.6 0.22 0.29 0.15 0.20
hypertension groups, indicating that hypertension has no impact on the effects of DEX on the hemodynamic parameters. Largely, the EtSEV and MAC of sevoflurane in DEX patients were significantly lower than those in control patients in both hypertension and non-hypertension groups, suggesting that DEX may reduce the anesthetic requirements during surgery, which is consistent with previously reported [12]. Subgroup analysis showed that no significant differences were observed in the EtSEV and MAC between hypertension patients and non-hypertension patients in both DEX group and control group. BIS is a factor reflecting the anesthesia depth. In the present study, BIS was controlled at 40–60. Analysis showed that BIS was comparable between control group and DEX group as well as between hypertension patients and non-hypertension patients. This avoids the influence of anesthesia depth on the hemodynamic parameters and TIH. IO and RI are parameters used to reflect the lung function and gas exchange. However, our results showed that both IO and RI remained unchanged after anesthesia and stable after tourniquet deflation. This implies that DEX has no influence on the lung function and gas exchange. Of note, we did not compare the recovery room time between two groups. Our experience showed that the DEX treated patients had a longer recovery room time as compared to DEX naïve patients if anesthesia was discontinued immediately after surgery. However, for patients receiving UKA in our study, the anesthesia is usually maintained for more than 30 min when arterial blood was collected for the detection of OI and RI and the subsequent evaluation of influence of DEX on the gas exchange. The DEX will be further metabolized and excreted. Thus, the DEX reduces gradually after surgery. Moreover, the EtSEV in DEX group was lower than that in control group. Thus, we speculate that the recovery room time in DEX group might be slightly longer than that in control group. There were still limitations in this study. There is no consensus on the TIH currently. In previous studies, a rise of more than 30% in SBP or DBP was used to define TIH. However, in these studies, BP was measured non-invasively. In the present study, BP was measured with an invasive method. Generally, non-invasive BP higher than 140 mmHg is a criterion for hypertension, and invasive BP is usually 15–20% higher than the non-invasive one. Thus, the threshold for hypertension might be 160 mmHg when invasive BP is measured. In addition, the BP usually reduces after general anesthesia. Although skin incision may slightly
Table 7 BIS, EtSEV and MAC of Patients in DEX Group (x ± s). Variable
Group
T0
T1
BIS
Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P
93.6 ± 3.9 93.6 ± 4.0 0.996
52.2 ± 49.3 ± 0.510 1.21 ± 1.19 ± 0.883 0.78 ± 0.78 ± 0.998
EtSEV (%) MAC
T2 12.9 12.0 0.48 0.45 0.32 0.29
41.4 ± 41.0 ± 0.885 1.61 ± 1.51 ± 0.168 1.03 ± 0.98 ± 0.376
T3 9.3 8.0 0.22 0.20 0.18 0.13
41.5 ± 39.8 ± 0.554 1.60 ± 1.52 ± 0.366 1.01 ± 0.99 ± 0.776
T4 10.1 7.4 0.28 0.26 0.18 0.15
42.8 ± 42.6 ± 0.936 1.57 ± 1.48 ± 0.256 1.01 ± 0.97 ± 0.507
T5 7.9 8.8 0.23 0.23 0.18 0.16
43.7 ± 41.5 ± 0.444 1.61 ± 1.48 ± 0.123 1.03 ± 0.97 ± 0.290
T6 6.8 8.9 0.27 0.22 0.20 0.16
42.4 ± 41.9 ± 0.867 1.52 ± 1.39 ± 0.107 0.97 ± 0.90 ± 0.180
7.9 8.1 0.23 0.25 0.15 0.16
Please cite this article as: Li Y-HY, et al, Influence of Dexmedetomidine on the Tourniquet Related Responses in Hypertension Patients Receiving Unilateral Knee Arthroplasty under General Anesthesia, J Arthroplasty (2015), http://dx.doi.org/10.1016/j.arth.2015.02.034
Y-H.Y. Li et al. / The Journal of Arthroplasty xxx (2015) xxx–xxx
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Table 8 OI and RI of Patients in Control Group (x ± s). Variable
Group
T1
RI
Non-hypertension Hypertension P Non-hypertension Hypertension P
0.546 0.525 0.832 464.6 444.9 0.783
OI
T2 ± 0.170 ± 0.150 ± 54.8 ± 64.6
0.503 0.497 0.904 441.7 421.6 0.823
T3 ± 0.164 ± 0.185 ± 55.2 ± 57.5
0.553 0.567 0.893 455.9 445.8 0.758
T4 ± 0.158 ± 0.160 ± 47.2 ± 53.3
0.598 0.603 0.915 463.5 454.2 0.812
± 0.202 ± 0.211 ± 61.2 ± 59.1
Table 9 OI and RI of Patients in DEX Group (x ± s). Variable
Group
T1
RI
Non-hypertension Hypertension P Non-hypertension Hypertension P
0.586 0.566 0.883 441.8 421.9 0.835
OI
T2 ± 0.142 ± 0.132 ± 69.8 ± 73.8
increase the BP, we measure the BP 20 min later. In this case, the increased blood pressure is mainly ascribed to tourniquet. In the present study, invasive blood pressure higher than about 160 mmHg at 20 min after inflation was used to define TIH. Moreover, Valli et al also found a positive correlation between the incidence of hypertension and age, duration of surgery and operative site [4]. In this study, we did not evaluate the correlation of TIH with duration of surgery, blood loss and other information. In addition, only one loading dose of DEX was used. Although the incidence of TIH in DEX patients was significantly lower than that in control patients, the incidence of TIH among hypertension patients was still as high as 48.0%. However, there were no marked differences in the hemodynamic parameters between hypertension group and non-hypertension group. Thus, whether it is required to adjust the dose of DEX in hypertension patients should be investigated in future studies. Furthermore, the sample size in the present study was relatively small, and future studies with large sample size are required to confirm our findings. Acknowledgements This study was partially supported by the Shanghai Natural Science Foundation (No. 15ZR1414200) and the Nursery Program of the Second Military Medical University (No. 2014QN16). We also thank Professors Wu YL, Qian QR and Li XH in the Department of Orthopedics in Changzheng Hospital for their kind help in the surgery. References 1. Gielen MJ, Stienstra R. Tourniquet hypertension and its prevention: a review. Reg Anaesth 1991;16:191. 2. Kaufman RD, Walts LF. Tourniquet-induced hypertension. Br J Anaesth 1982;54:333.
0.540 0.530 0.852 423.4 403.4 0.832
T3 ± 0.116 ± 0.106 ± 70.3 ± 81.7
0.674 0.644 0.813 454.4 444,4 0.914
T4 ± 0.206 ± 0.185 ± 59.8 ± 59.5
0.681 0.652 0.808 475.6 465.0 0.907
± 0.219 ± 0.182 ± 58.5 ± 55.4
3. Valli H, Rosenberg PH. Effects of three anaesthesia methods on haemodynamic responses connected with the use of thigh tourniquet in orthopaedic patients. Acta Anaesthesiol Scand 1985;29:142. 4. Valli H, Rosenberg PH, Kytta J, et al. Arterial hypertension associated with the use of a tourniquet with either general or regional anesthesia. Acta Anaesthesiol Scand 1987; 31:279. 5. Kam PC, Kavanagh R, Yoong FF. The arterial tourniquet: pathophysiological consequences and anaesthetic implications. Anaesthesia 2001;56:534. 6. Bostankolu E, Ayoglu H, Yurtlu S, et al. Dexmedetomidine did not reduce the effects of tourniquet-induced ischemia-reperfusion injury during general anesthesia. Kaohsiung J Med Sci 2013;29:75. 7. Savola J-M, Virtanen R. Central alpha2-adrenoceptors are highly stereoselective for dexmedetomidine, the dextro enantiomer of medetomidine. Eur J Pharmacol 1991; 195:193. 8. Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia 1999;54:146. 9. Chrysostomou C, Schmitt CG. Dexmedetomidine: sedation, analgesia and beyond. Expert Opin Drug Metab Toxicol 2008;4:619. 10. Lu Y, Zhang Y, Dong CS, et al. Preoperative dexmedetomidine prevents tourniquetinduced hypertension in orthopedic operation during general anesthesia. Kaohsiung J Med Sci 2013;29:271. 11. Lao HC, Tsai PS, Su JY, et al. Dexmedetomidine attenuates tourniquet-induced hyperdynamic response in patients undergoing lower limb surgeries: a randomized controlled study. J Surg Res 2013;179:e99. 12. Aho M, Erkola O, Kallio A, et al. Dexmedetomidine infusion for maintenance of anesthesia in patients undergoing abdominal hysterectomy. Anesth Analg 1992;75:940. 13. Working group of 2010 Guideline for the Prevention and Treatment of Hypertension in China. Guideline for the Prevention and Treatment of Hypertension in China. Chin J Hypertens 2011;19:701. 14. Hagenouw RR, Bridenbaugh PO, van Egmond J, et al. Tourniquet pain: a volunteer study. Anesth Analg 1986;65:1175. 15. Allee J, Muzaffar AR, Tobias JD. Dexmedetomidine controls the hemodynamic manifestations of tourniquet pain. Am J Ther 2011;18:e35. 16. Grounds M. Dexmedetomidine: phase III results. Proceedings from the 19th International Symposium on Intensive Care and Emergency Medicine; 1999; Brussels; 1999. p. 15. 17. Belleville JP, Ward DS, Bloor BC, et al. Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and metabolic rate. Anesthesiology 1992;77:1125.
Please cite this article as: Li Y-HY, et al, Influence of Dexmedetomidine on the Tourniquet Related Responses in Hypertension Patients Receiving Unilateral Knee Arthroplasty under General Anesthesia, J Arthroplasty (2015), http://dx.doi.org/10.1016/j.arth.2015.02.034
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Influence of Dexmedetomidine on the Tourniquet Related Responses in Hypertension Patients Receiving Unilateral Knee Arthroplasty under General Anesthesia Yong-Hua Y. Li, MD a,1, Yong-Qiang Y. Wang, MD b,1, Yi-Jie Y. Zhang, MD c,1, Dong-Yu D. Zheng, MD a, Liu Hu H., MD a, Mou-Li M. Tian, MD a a b c
Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, China Department of Anesthesiology, Shuguang Hospital, Traditional Chinese Medicine University, Shanghai, China Department of Anesthesiology, Qilu Hospital of Tsingdao City, Tsingdao, Shandong, China
a r t i c l e
i n f o
Article history: Received 6 November 2014 Accepted 24 February 2015 Available online xxxx Keywords: dexmedetomidine unilateral knee arthroplasty hemodynamic lung function hypertension
a b s t r a c t This study aimed to investigate the influence of dexmedetomidine (DEX) on the tourniquet related responses in hypertension patients receiving unilateral knee arthroplasty (UKA) under general anesthesia. Results showed that the incidence of tourniquet induced hypertension (TIH), hemodynamics, MAC and EtSEV in DEX group were significantly lower than those in control group, regardless of hypertension. However, significant differences in TIH, hemodynamics, minimum alveolar concentration (MAC) and end-tidal sevoflurane (EtSEV) were not observed between hypertension patients and non-hypertension patients in both control group and DEX group. Moreover, oxygen index (OI) and respiratory index (RI) remained unchanged after deflation and DEX failed to affect OI and RI within 30 min after deflation, regardless of hypertension. Taken together, DEX may significantly improve the hemodynamics, which is independent of pre-existing hypertension. © 2015 Elsevier Inc. All rights reserved.
Surgery of the extremities is frequently performed after exsanguination of the limb followed by inflation of a tourniquet, aiming to obtain bloodless operating conditions and to prevent unnecessary blood loss. However, prolonged tourniquet inflation may cause a gradual rise in blood pressure, which is also known as tourniquet induced hypertension (TIH). TIH occurs more frequently in patients receiving general anesthesia and/or lower limb surgery [1]. There is no consensus on the definition of TIH. In previous studies, TIH was defined as a rise of more than 30% in systolic or diastolic blood pressure [2,3]. According to this definition, the incidence of TIH in general anesthesia varies among studies and patients receiving different types of anesthesia. Kaufman and Walts reported that the frequency of TIH was 11% in a group of 500 patients whose operations involved the use of a tourniquet in lower limbs surgery [2]. In a retrospective study on 699 patients receiving orthopedic surgery using prolonged tourniquet inflation with a minimum of one hour of anesthesia, hypertension was found in 67% of patients receiving general anesthesia, 18.6% of the patients receiving intravenous regional anesthesia (IVRA), 2.7% of the patients operated under spinal anesthesia and 2.5% of the patients receiving a brachial plexus anesthetic [4]. 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 http://dx.doi.org/10.1016/j.arth.2015.02.034 Reprint requests: Mou-Li Tian, MD, and Liu Hu, MD, Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, Huangpu District, 200003, Shanghai, China. 1 All contribute to this work equally.
TIH during the surgery may increase the risk for cardiovascular events (such as coronary ischemia and arrhythmia), especially in patients with advanced age, concomitant hypertension, ischemic heart disease and atherosclerosis [5]. Moreover, tourniquet inflation–deflation induced ischemia and reperfusion may cause damage to the lung, leading to the impairment to the gas exchange of the lung [6]. Thus, to deeply investigate the tourniquet related hemodynamic responses and ischemia–reperfusion injury is important for patients receiving limb surgery under general anesthesia. Dexmedetomidine (DEX), an imidazole compound, is the pharmacologically active dextroisomer of medetomidine [7], which displays specific and selective α2-adrenoceptor agonism. Since its release in the US market in late 1999, it has gained remarkable attention in the adult, pediatric and geriatric populations, predominantly because of its minimal respiratory depression. Besides the sedative, analgesic and anxiolytic properties [8], studies in recent years also reveal that DEX has its potential in many other clinical scenarios, including neuroprotection, cardioprotection and renoprotection, with promising results [9]. Theoretically, DEX may exert significant effects on attenuating tourniquet-induced hyperdynamic responses including TIH, which has been confirmed in several studies [10,11]. In addition, pre-operative use of DEX is also helpful to reduce the dose of anesthetics [12]. However, in hypertension patients, the impact of DEX is still unclear because hypertension patients were usually excluded from some studies [10,11]. In the present study, patients with or without hypertension receiving elective unilateral knee arthroplasty (UKA) were recruited to investigate
http://dx.doi.org/10.1016/j.arth.2015.02.034 0883-5403/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Li Y-HY, et al, Influence of Dexmedetomidine on the Tourniquet Related Responses in Hypertension Patients Receiving Unilateral Knee Arthroplasty under General Anesthesia, J Arthroplasty (2015), http://dx.doi.org/10.1016/j.arth.2015.02.034
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Table 1 Demographic Data in Control Group and DEX Group.
Table 3 Incidence of TIH in Different Groups (n, %).
Variable
Control Group (n = 39) DEX Group (n = 41)
Group
Control
DEX
Total
Age (years) Height (cm) Body weight (kg) BMI (kg/cm2) Gender (M/F) Tourniquet time (min) History of hypertension (yes/no)
66.1 ± 7.5 160.3 ± 6.9 65.2 ± 10.2 25.3 ± 3.4 10/29 76.3 ± 13.8 18/21
Non-hypertension Hypertension Total
14 (66.7%) 14 (77.8%) 28 (71.8%)
2 (12.5%) 12 (48.0%) 14 (34.1%)
16 (43.2%) 26 (60.5%)
65.0 ± 7.9 159.7 ± 6.6 67.7 ± 11.0 26.4 ± 3.5 9/32 79.7 ± 11.3 25/16
whether hypertension may influence the hemodynamics and inhaled anesthesia related parameters following pre-operative use of DEX. Materials and methods
Following anesthesia induction, DEX at a loading dose of 1 μg/kg was injected via a pump within 20 min, and maintenance was done with DEX at 0.4 μg/kg/h until tourniquet deflation. In control group, normal saline of equal volume was injected. Adequate muscle relaxation was maintained during surgery to avoid the changes in BP and HR. TIH was defined as invasive SBP higher than 160 mmHg for at least 1 min at 20 min after tourniquet inflation. In addition, the rate pressure product (RPP) was also calculated.
Inclusion of patients A total of 80 patients (ASA grade I-III) receiving elective unilateral knee arthroplasty were recruited from the Department of Joint Surgery from July 2011 to January 2012. The mean age was 65.4 ± 7.8 years (range: 46–75 years). There were 19 males and 61 females. In addition, 43 patients had a history of doctor diagnosed hypertension. Hypertension was diagnosed according to the Guideline for the Prevention and Treatment of Hypertension in China [13]. Exclusion criteria: (1) Patients were allergic to DEX or other drugs used in the present study; (2) patients had respiratory infections recently, chronic cough, asthma and chronic obstructive lung disease; (3) patients had severe liver and/or kidney dysfunction; (4) patients had severe sinus bradycardia (b50 beats/min); (5) patients had type II second-degree atrioventricular block. This study was registered in Chinese Clinical Trial Register (ChiCTRTRC-11001714) and informed consent was obtained from each patient before study. The whole protocol was approved by the Ethics Committee of Chinese Clinical Trial Register (ChiECRCT-2011044). Treatments Patients were randomly divided into control group and DEX group. All the patients received food and water deprivation for 8 h before surgery. Before anesthesia, an access to the upper limb vein was prepared for the fluid infusion and detection of bispectral index (BIS). The heart rate (HR) was routinely monitored and the blood pressure (BP; systolic blood pressure, SBP) was measured invasively via the left radial artery. End-tidal concentration of sevoflurane (EtSEV) and minimal alveolar concentration (MAC) were recorded during anesthesia. Before anesthesia induction, Ringer's acetate was infused at 5 ml/kg. For anesthesia induction, midazolam at 0.05 mg/kg, propofol at 1 mg/kg, fentanyl at 3 μg/kg and cis-atracurium at 0.3 mg/kg were injected, followed by tracheal intubation and subsequent mechanical ventilation via an anesthesia machine when the BIS reduced to lower than 60. The tidal volume was 10 ml/kg and respiratory rate was 12 breaths/min. Anesthesia was maintained with sevoflurane, and all patients' lungs were mechanically ventilated with 1 L/min fresh gas. The anesthesia depth was adjusted to maintain the BIS at 40–60. The liquid crystal was infused at 6 ml/kg/h via a micropump during surgery. Table 2 Demographics of Hypertension Patients and Non-Hypertension Patients. Variable
Hypertension (n = 43)
Non-Hypertension (n = 37)
Age (years) Height (cm) Body weight (kg) BMI (kg/cm2) Gender (M/F) Tourniquet time (min)
66.0 ± 6.8 160.4 ± 6.4 69.2 ± 11.6 26.7 ± 3.4 11/32 78.7 ± 12.8
64.8 ± 8.8 159.7 ± 7.4 68.1 ± 9.0 26.9 ± 3.3 8/29 77.2 ± 12.9
Application of tourniquet ZJ-1 numerical control pneumatic tourniquet (width: 71 mm) was used. Following anesthesia, the tourniquet was wrapped at the root of thigh. Mechanical limb exsanguination was performed with an elastic bandage prior to commencing surgery, followed by inflation.
Observations Demographics including age, gender, height and body weight as well as the history of doctor diagnosed hypertension were recorded. The hemodynamic parameters (HR, SBP, mean arterial pressure [MAP], cardiac index [CI], stroke volume index [SVI] and systemic vascular resistance index [SVRI]) were detected or calculated before anesthesia induction (T0) and at different time points (0 [T1], 20 [T2], 30 [T3], 40 [T4], 50 [T5] and 60 min [T6]) after inflation. In addition, the EtSEV and MAC of sevoflurane were also recorded. One minute before and within 30 min after deflation (5, 15 and 30 min), the arterial partial pressure of oxygen (PaO2), fraction of inspired oxygen (FiO2) and alveolo-arterial oxygen partial pressure difference (P(A-a)O2) were measured, followed by calculation of oxygenation index (OI) and respiratory index (RI).
Statistical analysis Quantitative data are expressed as mean ± standard deviation (SD). Comparisons were done with repeated-measures analysis of variance of variance for data collected at different time points and with analysis of variance for those in a specific group. Qualitative data were compared with chi square test. Statistical analysis was performed with SPSS version 18.0, and a value of P b 0.05 was considered statistically significant.
Results General information There were no marked differences in the gender, age, body weight, height, BMI, tourniquet time and history of hypertension between control group and DEX group (P N 0.05; Table 1), and hypertension patients and non-hypertension also matched in the gender, age, body weight, height, BMI and tourniquet time (P N 0.05; Table 2). There were no marked differences in the use of Ringer's acetate and liquid crystal. Loading dose (1 μg/kg) of DEX was injected via a pump for 20 min, and no patients had the heart rate of b 45 bpm. Patients were closely monitored, and there were no complications related to hypertension.
Please cite this article as: Li Y-HY, et al, Influence of Dexmedetomidine on the Tourniquet Related Responses in Hypertension Patients Receiving Unilateral Knee Arthroplasty under General Anesthesia, J Arthroplasty (2015), http://dx.doi.org/10.1016/j.arth.2015.02.034
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Table 4 Hemodynamic Parameters of Patients in Control Group (x ± s). Variables
Group
T0
T1
T2
T3
T4
T5
T6
HR (bpm)
Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P
71.8 ± 8.0 74.9 ± 11.1 0.323 157.1 ± 16.2 165.7 ± 18.9 0.133 105.0 ± 11.2 108.6 ± 11.4 0.326 11,259 ± 1586 12,336 ± 2294 0.093 3.30 ± 0.78 3.18 ± 0.75 0.612 46.4 ± 10.9 44.4 ± 10.2 0.563 2690 ± 693 2700 ± 476 0.960
59.4 ± 9.7 58.0 ± 8.0 0.622 116.0 ± 19.2 117.2 ± 25.0 0.864 82.7 ± 15.9 81.2 ± 18.3 0.786 6999 ± 2339 6885 ± 2120 0.842 2.48 ± 0.59 2.43 ± 0.58 0.818 42.0 ± 9.0 42.6 ± 9.0 0.864 2587 ± 503 2635 ± 342 0.746
67.0 ± 9.2 65.0 ± 11.7 0.565 153.4 ± 22.1 155.5 ± 21.9 0.771 109.6 ± 13.8 109.5 ± 17.0 0.988 10,284 ± 2111 10,258 ± 2509 0.964 2.90 ± 0.40 2.79 ± 0.49 0.473 44.3 ± 7.3 45.3 ± 9.0 0.703 2915 ± 512 2958 ± 551 0.810
67.6 ± 9.6 72.8 ± 20.8 0.311 152.4 ± 22.4 155.2 ± 28.2 0.732 109.0 ± 14.7 111.8 ± 14.9 0.553 10,331 ± 2265 11,145 ± 3082 0.973 3.00 ± 0.70 2.94 ± 0.60 0.777 44.9 ± 9.1 45.4 ± 10.5 0.885 2799 ± 604 2909 ± 585 0.582
65.7 ± 8.6 67.3 ± 13.1 0.646 149.2 ± 17.1 151.6 ± 19.8 0.691 106.6 ± 12.0 106.7 ± 14.5 0.981 9840 ± 1882 10,330 ± 2703 0.349 2.96 ± 0.46 2.85 ± 0.38 0.453 45.3 ± 6.7 44.3 ± 8.4 0.696 2787 ± 449 2849 ± 511 0.698
65.2 ± 10.5 68.4 ± 15.3 0.445 146.9 ± 20.4 149.4 ± 22.0 0.717 104.3 ± 15.1 105.8 ± 17.2 0.774 9687 ± 2574 10,356 ± 3504 0.511 3.02 ± 0.65 2.84 ± 0.45 0.365 46.4 ± 6.9 43.9 ± 9.0 0.356 2591 ± 734 2796 ± 468 0.337
64.7 ± 10.0 65.2 ± 10.7 0.879 142.0 ± 19.1 144.8 ± 20.4 0.651 102.2 ± 14.2 103.0 ± 12.8 0.854 9276 ± 2306 9481 ± 2130 0.504 3.04 ± 0.68 2.71 ± 0.44 0.103 47.2 ± 7.1 43.6 ± 9.8 0.195 2629 ± 459 2932 ± 601 0.091
SBP (mmHg) MAP (mmHg) RPP (bpm × mmHg) CI (L/min/m2) SVI (ml/b/m2) SVRI (kPa-s-m2/cmL)
Incidence of TIH BIS, EtSEV and MAC at different time points The incidence of TIH was 71.8% and 34.1% in control group and DEX group, respectively, showing marked difference (P b 0.01, Table 3). In control group, the incidence of TIH was 66.7% and 77.8% in nonhypertension patients and hypertension patients, respectively, suggesting no significant difference (P N 0.05). However, marked difference was observed in the incidence of TIH between non-hypertension patients and hypertension patients in DEX group (12.5% and 48.0%; P b 0.05).
In DEX patients, EtSEV at T4-T6 and MAC at T3-T6 were significantly lower than those in control patients in both hypertension and nonhypertension groups (P b 0.05). No marked differences in EtSEV at T2-T6 were observed between hypertension patients and non-hypertension patients in both control group and DEX group (P N 0.05) (Tables 6 and 7). In addition, BIS remained stable after anesthesia, and was comparable between control group and DEX group as well as between hypertension patients and non-hypertension patients (P N 0.05) (Tables 6 and 7).
Hemodynamic data at different time points The HR, SBP, RPP and CI at T2-T6 increased significantly in control group and DEX group when compared with those at T0 (P b 0.01). In addition, the HR, SBP, RPP and CI at T2-T6 in DEX patients reduced markedly when compared with control patients (P b 0.05 or b 0.01), in both hypertension and non-hypertension groups. However, the HR, SBP, RPP and CI at T2-T6 were comparable between hypertension patients and non-hypertension patients in both control group and DEX group (P N 0.05; Tables 4 and 5).
OI and RI after deflation The OI and RI remained unchanged after deflation. In addition, there were no significant differences in the OI and RI between control patients and DEX patients as well as between hypertension patients and nonhypertension patients (P N 0.05; Tables 8 and 9).
Table 5 Hemodynamic Parameters of Patients in DEX Group (x ± s). Variable
Group
T0
T1
T2
T3
T4
T5
T6
HR (bpm)
Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P
73.4 ± 12.7 76.1 ± 12.4 0.514 147.9 ± 17.3 176.9 ± 26.9 0.000 101.6 ± 13.9 114.3 ± 15.3 0.010 10,849 ± 2328 13,534 ± 3411 0.009 3.33 ± 0.75 3.44 ± 0.63 0.611 46.5 ± 7.9 47.5 ± 11.4 0.753 2391 ± 502 2773 ± 530 0.031⁎
54.8 ± 7.7 54.2 ± 7.4 0.814 130.8 ± 23.7 139.8 ± 29.9 0.314 93.2 ± 16.8 94.3 ± 20.9 0.861 7168 ± 8379 7569 ± 1965 0.517 2.61 ± 0.58 2.67 ± 0.89 0.813 47.6 ± 6.3 49.8 ± 13.9 0.572 2814 ± 511 2951 ± 508 0.418
59.8 ± 7.1 59.7 ± 10.3 0.992 139.7 ± 14.4 147.8 ± 23.3 0.218 102.7 ± 9.1 105.8 ± 15.6 0.469 8379 ± 1525 8901 ± 2415 0.445 2.69 ± 0.55 2.77 ± 0.64 0.674 43.1 ± 5.0 46.6 ± 7.8 0.124 3064 ± 484 3045 ± 522 0.910
60.1 ± 8.4 58.0 ± 6.5 0.392 137.0 ± 15.4 137.8 ± 22.5 0.906 100.4 ± 10.8 98.4 ± 15.6 0.654 8282 ± 1714 8007 ± 1630 0.609 2.73 ± 0.62 2.64 ± 0.59 0.632 43.2 ± 5.0 44.7 ± 7.8 0.505 2984 ± 570 3020 ± 444 0.830
60.3 ± 9.0 58.2 ± 8.6 0.455 137.8 ± 18.4 141.3 ± 23.5 0.615 101.7 ± 12.5 102.5 ± 16.2 0.869 8391 ± 2078 8294 ± 2206 0.890 2.74 ± 0.85 2.56 ± 0.46 0.375 43.4 ± 6.8 45.7 ± 9.2 0.403 3010 ± 584 3061 ± 552 0.786
57.8 ± 7.0 58.1 ± 8.2 0.915 133.0 ± 16.1 139.9 ± 25.4 0.340 97.1 ± 11.2 96.5 ± 18.4 0.916 7735 ± 1587 8211 ± 2348 0.481 2.63 ± 0.68 2.57 ± 0.55 0.782 43.2 ± 4.2 44.9 ± 9.1 0.491 2972 ± 507 2943 ± 475 0.858
56.9 ± 7.7 57.0 ± 8.9 0.975 124.5 ± 15.7 137.3 ± 26.1 0.085 93.3. ± 11.2 96.8 ± 19.9 0.520 7141 ± 1684 7873 ± 2222 0.267 2.69 ± 0.68 2.55 ± 0.42 0.435 46.9 ± 11.8 45.6 ± 7.0 0.675 2800 ± 395 2932 ± 523 0.400
SBP (mmHg) MAP (mmHg) RPP (bpm × mmHg) CI (L/min/m2) SVI (ml/b/m2) SVRI (kPa-s-m2/cmL)
Please cite this article as: Li Y-HY, et al, Influence of Dexmedetomidine on the Tourniquet Related Responses in Hypertension Patients Receiving Unilateral Knee Arthroplasty under General Anesthesia, J Arthroplasty (2015), http://dx.doi.org/10.1016/j.arth.2015.02.034
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Table 6 BIS, EtSEV and MAC of Patients in Control Group (x ± s). Variable
Group
T0
T1
BIS
Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P
91.5 ± 4.2 91.2 ± 6.0 0.863
55.9 ± 54.5 ± 0.725 1.01 ± 1.16 ± 0.357 0.67 ± 0.78 ± 0.326
EtSEV (%) MAC
T2 10.0 10.3 0.47 0.49 0.30 0.34
44.9 ± 46.6 ± 0.643 1.64 ± 1.59 ± 0.435 1.06 ± 1.04 ± 0.851
Discussion Arterial tourniquets are used for extremity surgery to reduce blood loss and provide good operating conditions. However, prolong tourniquet inflation during general anesthesia causes increases in heart rate and blood pressure, which commonly lead the anesthetists to increase the depth of anesthesia. This clinical syndrome is commonly referred to as “tourniquet pain” [14]. DEX is a potent α2-adrenoceptor agonist with 8 times higher affinity for the α2-adrenoceptor than clonidine [9]. DEX has shown sedative, analgesic and anxiolytic effects in healthy volunteers or postsurgical patients in the intensive care unit [9]. Theoretically, DEX is able to attenuate the “tourniquet pain” according to its pathogenesis, which has been confirmed in previous studies [10,11,15]. However, hypertension was used as an exclusion criterion in previous studies [10,11], and thus patients with hypertension were often not recruited. In the present study, we investigated whether the pre-existing hypertension affects the protective effects of DEX on the “tourniquet pain”. Theoretically, the anti-hypertensive effect of DEX may continue for about 2 h (half-life). However, the tourniquet time was no longer than 90 min for patients receiving UKA in our hospital. So this study focused on the hemodynamics within 60 min after inflation. Our results showed that the incidence of TIH was 66.7% in non-hypertension patients of control group, which was consistent with a previous study [4]. In addition, pre-operative treatment with DEX was helpful to reduce the incidence of TIH, which was independent of hypertension. This suggests that hypertension has no influence on the protective effect of DEX on the TIH. In addition, in control group, the incidence of TIH was comparable between hypertension patients and non-hypertension patients, indicating that pre-existing hypertension is not associated with TIH. Of note, the reduction in the incidence of TIH was higher in nonhypertension patients than in hypertension patients following DEX therapy, indicating that hypertension has influence on the incidence of TIH after DEX. The HR, SBP, RPP and CI increased after tourniquet inflation. In addition, these parameters after tourniquet inflation in control group were significantly higher than those in DEX group, regardless of hypertension, suggesting that DEX is able to reduce hemodynamic parameters, which has been confirmed in previous studies [15–17]. However, there were no marked differences between hypertension and non-
T3 9.2 9.1 0.18 0.24 0.11 0.18
43.3 ± 48.0 ± 0.174 1.66 ± 1.57 ± 0.323 1.08 ± 1.06 ± 0.712
T4 8.7 8.9 0.20 0.27 0.12 0.17
45.5 ± 47.5 ± 0.450 1.66 ± 1.66 ± 0.919 1.07 ± 1.09 ± 0.733
T5 6.7 7.0 0.21 0.27 0.16 0.18
45.9 ± 45.1 ± 0.742 1.66 ± 1.64 ± 0.798 1.07 ± 1.07 ± 0.989
T6 6.9 6.4 0.17 0.26 0.13 0.19
43.9 ± 46.3 ± 0.390 1.59 ± 1.66 ± 0.445 1.04 ± 1.10 ± 0.382
6.8 7.6 0.22 0.29 0.15 0.20
hypertension groups, indicating that hypertension has no impact on the effects of DEX on the hemodynamic parameters. Largely, the EtSEV and MAC of sevoflurane in DEX patients were significantly lower than those in control patients in both hypertension and non-hypertension groups, suggesting that DEX may reduce the anesthetic requirements during surgery, which is consistent with previously reported [12]. Subgroup analysis showed that no significant differences were observed in the EtSEV and MAC between hypertension patients and non-hypertension patients in both DEX group and control group. BIS is a factor reflecting the anesthesia depth. In the present study, BIS was controlled at 40–60. Analysis showed that BIS was comparable between control group and DEX group as well as between hypertension patients and non-hypertension patients. This avoids the influence of anesthesia depth on the hemodynamic parameters and TIH. IO and RI are parameters used to reflect the lung function and gas exchange. However, our results showed that both IO and RI remained unchanged after anesthesia and stable after tourniquet deflation. This implies that DEX has no influence on the lung function and gas exchange. Of note, we did not compare the recovery room time between two groups. Our experience showed that the DEX treated patients had a longer recovery room time as compared to DEX naïve patients if anesthesia was discontinued immediately after surgery. However, for patients receiving UKA in our study, the anesthesia is usually maintained for more than 30 min when arterial blood was collected for the detection of OI and RI and the subsequent evaluation of influence of DEX on the gas exchange. The DEX will be further metabolized and excreted. Thus, the DEX reduces gradually after surgery. Moreover, the EtSEV in DEX group was lower than that in control group. Thus, we speculate that the recovery room time in DEX group might be slightly longer than that in control group. There were still limitations in this study. There is no consensus on the TIH currently. In previous studies, a rise of more than 30% in SBP or DBP was used to define TIH. However, in these studies, BP was measured non-invasively. In the present study, BP was measured with an invasive method. Generally, non-invasive BP higher than 140 mmHg is a criterion for hypertension, and invasive BP is usually 15–20% higher than the non-invasive one. Thus, the threshold for hypertension might be 160 mmHg when invasive BP is measured. In addition, the BP usually reduces after general anesthesia. Although skin incision may slightly
Table 7 BIS, EtSEV and MAC of Patients in DEX Group (x ± s). Variable
Group
T0
T1
BIS
Non-hypertension Hypertension P Non-hypertension Hypertension P Non-hypertension Hypertension P
93.6 ± 3.9 93.6 ± 4.0 0.996
52.2 ± 49.3 ± 0.510 1.21 ± 1.19 ± 0.883 0.78 ± 0.78 ± 0.998
EtSEV (%) MAC
T2 12.9 12.0 0.48 0.45 0.32 0.29
41.4 ± 41.0 ± 0.885 1.61 ± 1.51 ± 0.168 1.03 ± 0.98 ± 0.376
T3 9.3 8.0 0.22 0.20 0.18 0.13
41.5 ± 39.8 ± 0.554 1.60 ± 1.52 ± 0.366 1.01 ± 0.99 ± 0.776
T4 10.1 7.4 0.28 0.26 0.18 0.15
42.8 ± 42.6 ± 0.936 1.57 ± 1.48 ± 0.256 1.01 ± 0.97 ± 0.507
T5 7.9 8.8 0.23 0.23 0.18 0.16
43.7 ± 41.5 ± 0.444 1.61 ± 1.48 ± 0.123 1.03 ± 0.97 ± 0.290
T6 6.8 8.9 0.27 0.22 0.20 0.16
42.4 ± 41.9 ± 0.867 1.52 ± 1.39 ± 0.107 0.97 ± 0.90 ± 0.180
7.9 8.1 0.23 0.25 0.15 0.16
Please cite this article as: Li Y-HY, et al, Influence of Dexmedetomidine on the Tourniquet Related Responses in Hypertension Patients Receiving Unilateral Knee Arthroplasty under General Anesthesia, J Arthroplasty (2015), http://dx.doi.org/10.1016/j.arth.2015.02.034
Y-H.Y. Li et al. / The Journal of Arthroplasty xxx (2015) xxx–xxx
5
Table 8 OI and RI of Patients in Control Group (x ± s). Variable
Group
T1
RI
Non-hypertension Hypertension P Non-hypertension Hypertension P
0.546 0.525 0.832 464.6 444.9 0.783
OI
T2 ± 0.170 ± 0.150 ± 54.8 ± 64.6
0.503 0.497 0.904 441.7 421.6 0.823
T3 ± 0.164 ± 0.185 ± 55.2 ± 57.5
0.553 0.567 0.893 455.9 445.8 0.758
T4 ± 0.158 ± 0.160 ± 47.2 ± 53.3
0.598 0.603 0.915 463.5 454.2 0.812
± 0.202 ± 0.211 ± 61.2 ± 59.1
Table 9 OI and RI of Patients in DEX Group (x ± s). Variable
Group
T1
RI
Non-hypertension Hypertension P Non-hypertension Hypertension P
0.586 0.566 0.883 441.8 421.9 0.835
OI
T2 ± 0.142 ± 0.132 ± 69.8 ± 73.8
increase the BP, we measure the BP 20 min later. In this case, the increased blood pressure is mainly ascribed to tourniquet. In the present study, invasive blood pressure higher than about 160 mmHg at 20 min after inflation was used to define TIH. Moreover, Valli et al also found a positive correlation between the incidence of hypertension and age, duration of surgery and operative site [4]. In this study, we did not evaluate the correlation of TIH with duration of surgery, blood loss and other information. In addition, only one loading dose of DEX was used. Although the incidence of TIH in DEX patients was significantly lower than that in control patients, the incidence of TIH among hypertension patients was still as high as 48.0%. However, there were no marked differences in the hemodynamic parameters between hypertension group and non-hypertension group. Thus, whether it is required to adjust the dose of DEX in hypertension patients should be investigated in future studies. Furthermore, the sample size in the present study was relatively small, and future studies with large sample size are required to confirm our findings. Acknowledgements This study was partially supported by the Shanghai Natural Science Foundation (No. 15ZR1414200) and the Nursery Program of the Second Military Medical University (No. 2014QN16). We also thank Professors Wu YL, Qian QR and Li XH in the Department of Orthopedics in Changzheng Hospital for their kind help in the surgery. References 1. Gielen MJ, Stienstra R. Tourniquet hypertension and its prevention: a review. Reg Anaesth 1991;16:191. 2. Kaufman RD, Walts LF. Tourniquet-induced hypertension. Br J Anaesth 1982;54:333.
0.540 0.530 0.852 423.4 403.4 0.832
T3 ± 0.116 ± 0.106 ± 70.3 ± 81.7
0.674 0.644 0.813 454.4 444,4 0.914
T4 ± 0.206 ± 0.185 ± 59.8 ± 59.5
0.681 0.652 0.808 475.6 465.0 0.907
± 0.219 ± 0.182 ± 58.5 ± 55.4
3. Valli H, Rosenberg PH. Effects of three anaesthesia methods on haemodynamic responses connected with the use of thigh tourniquet in orthopaedic patients. Acta Anaesthesiol Scand 1985;29:142. 4. Valli H, Rosenberg PH, Kytta J, et al. Arterial hypertension associated with the use of a tourniquet with either general or regional anesthesia. Acta Anaesthesiol Scand 1987; 31:279. 5. Kam PC, Kavanagh R, Yoong FF. The arterial tourniquet: pathophysiological consequences and anaesthetic implications. Anaesthesia 2001;56:534. 6. Bostankolu E, Ayoglu H, Yurtlu S, et al. Dexmedetomidine did not reduce the effects of tourniquet-induced ischemia-reperfusion injury during general anesthesia. Kaohsiung J Med Sci 2013;29:75. 7. Savola J-M, Virtanen R. Central alpha2-adrenoceptors are highly stereoselective for dexmedetomidine, the dextro enantiomer of medetomidine. Eur J Pharmacol 1991; 195:193. 8. Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia 1999;54:146. 9. Chrysostomou C, Schmitt CG. Dexmedetomidine: sedation, analgesia and beyond. Expert Opin Drug Metab Toxicol 2008;4:619. 10. Lu Y, Zhang Y, Dong CS, et al. Preoperative dexmedetomidine prevents tourniquetinduced hypertension in orthopedic operation during general anesthesia. Kaohsiung J Med Sci 2013;29:271. 11. Lao HC, Tsai PS, Su JY, et al. Dexmedetomidine attenuates tourniquet-induced hyperdynamic response in patients undergoing lower limb surgeries: a randomized controlled study. J Surg Res 2013;179:e99. 12. Aho M, Erkola O, Kallio A, et al. Dexmedetomidine infusion for maintenance of anesthesia in patients undergoing abdominal hysterectomy. Anesth Analg 1992;75:940. 13. Working group of 2010 Guideline for the Prevention and Treatment of Hypertension in China. Guideline for the Prevention and Treatment of Hypertension in China. Chin J Hypertens 2011;19:701. 14. Hagenouw RR, Bridenbaugh PO, van Egmond J, et al. Tourniquet pain: a volunteer study. Anesth Analg 1986;65:1175. 15. Allee J, Muzaffar AR, Tobias JD. Dexmedetomidine controls the hemodynamic manifestations of tourniquet pain. Am J Ther 2011;18:e35. 16. Grounds M. Dexmedetomidine: phase III results. Proceedings from the 19th International Symposium on Intensive Care and Emergency Medicine; 1999; Brussels; 1999. p. 15. 17. Belleville JP, Ward DS, Bloor BC, et al. Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and metabolic rate. Anesthesiology 1992;77:1125.
Please cite this article as: Li Y-HY, et al, Influence of Dexmedetomidine on the Tourniquet Related Responses in Hypertension Patients Receiving Unilateral Knee Arthroplasty under General Anesthesia, J Arthroplasty (2015), http://dx.doi.org/10.1016/j.arth.2015.02.034