Intraoperative sedation with dexmedetomidine is

The Clinical Journal of Pain Publish Ahead of Print DOI:10.1097/AJP.0000000000000605

Intraoperative sedation with dexmedetomidine is superior to propofol for elderly patients undergoing hip arthroplasty: A prospective randomized controlled study. 1.

Bin Mei, M.D. Institution Address: Department of anesthesiology, the second affiliated hospital of Anhui medical university, No. 678 Furong road, Hefei city, Anhui province, China.

2. Gaige Meng, M.D. Institution Address: Department of anesthesiology, the first affiliated hospital of Anhui medical university, No. 218 Jixi road, Hefei city, Anhui province, China. 3.

Guanghong Xu, M.D. Ph.D. Institution Address: Department of anesthesiology, the first affiliated hospital of Anhui medical university, No. 218 Jixi road, Hefei city, Anhui province, China.

4.

Xinqi Cheng, M.D. Institution Address: Department of anesthesiology, the first affiliated hospital of Anhui

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medical university, No. 218 Jixi road, Hefei city, Anhui province, China. 5. Shishou Chen, M.D. Institution Address: Department of anesthesiology, the first affiliated hospital of Anhui medical university, No. 218 Jixi road, Hefei city, Anhui province, China. 6. Ye Zhang, M.D. Ph.D. Institution Address: Department of anesthesiology, the second affiliated hospital of Anhui medical university, No. 678 Furong road, Hefei city, Anhui province, China. 7. Ming Zhang, M.MED. Ph.D. Institution Address: Department of Anatomy, Otago School of Biomedical Sciences, P.O. Box 913, 270 Great King Street, Dunedin 9054, New Zealand. 8. Xuesheng Liu, M.D. Ph.D. Institution Address: Department of anesthesiology, the first affiliated hospital of Anhui medical university, No. 218 Jixi road, Hefei city, Anhui province, China. 9. Erwei Gu, M.D. Institution Address: Department of anesthesiology, the first affiliated hospital of Anhui medical university, No. 218 Jixi road, Hefei city, Anhui province, China. Corresponding Author Ye Zhang, Department of anesthesiology, the second affiliated hospital of Anhui medical university, Hefei city, Anhui province, China.


No. 678 Furong road, Hefei city, Anhui province, China. Postcode: 230601 Phone: +8655162922057 FAX: +8655163869480 Email: [email protected] Conflicts of interest Dr. Bin Mei and Dr. Gaige Meng contributed equally to this study. No other conflicts of interest. Sources of support that require acknowledgment: This work was supported by the National Natural Science Foundation of China (81171031, 81571039).


ABSTRACT Background: Peripheral nerve block is a preferable method for elderly patients receiving hip arthroplasty. Sedation with dexmedetomidine may reduce postoperative delirium. The aim of this study was to investigate whether intraoperative sedation with dexmedetomidine, as a supplementary to peripheral nerve block for elderly patients receiving total hip arthroplasty, can decrease the prevalence of postoperative delirium. Methods: A prospective, randomized controlled study was conducted with patients 65 years of age or older who underwent total hip arthroplasty between June 2016 and June 2017. The patients were randomly assigned to receive a lumbosacral plexus plus T12 paravertebral block supplemented with propofol or dexmedetomidine for sedation. Incidence of postoperative delirium was the primary endpoint and was determined with the Confusion Assessment Method, and incidence of postoperative cognitive dysfunction was assessed with the Mini-Mental State Examination. The time of ambulation, discharge time, and complications over a 30-day postsurgery period were also recorded. Results: 296 patients were randomly assigned to two groups. The patients sedated with dexmedetomidine had lower incidences of postoperative delirium and postoperative cognitive dysfunction and were out of bed and discharged sooner than the patients sedated with propofol. There was no difference in complications between the two groups. Conclusion: As a supplementary to peripheral nerve block, intraoperative sedation with dexmedetomidine could be associated with a lower incidence of POD, which may have benefits on reducing the incidence of early postoperative cognitive dysfunction and offering a better short-term recovery for elderly patients receiving hip arthroplasty. Keywords: total hip arthroplasty / peripheral nerve block /sedation / dexmedetomidine /patient care


INTRODUCTION The increasing incidence of postoperative delirium (POD) in the elderly patients receiving hip arthroplasty is a risk to deteriorate outcomes of these patients. The prevalence of POD ranges from 16% to 62% in the elderly patients receiving hip fracture repair, and is related to poor function recovery, increased length of stay in hospital, increased frequency of early postoperative cognitive dysfunction (POCD) and mortality.1 Regional anesthesia (RA) was considered as the preferable method for elderly and contraindicated patients for the advantage of avoidance of general anesthesia (GA) drugs, especially opioids, which may be related to POD.2 Also, RA may also facilitate the restoration of oral intake and functional training in patients, both of which are vital to recovery.3, 4 Unfortunately, however, complications, contraindications and the difficulty of puncture in some elderly patients limited the application of neuraxial anesthesia.5, 6 Lumbosacral plexus plus T12 paravertebral block was reported to be a satisfied anesthesia method for total hip arthroplasty.7 As a supplement to RA, intraoperative sedation has benefits of avoiding postural discomfort, preventing intraoperative recall, and reducing sympathetic and parasympathetic reflexes, thus is necessary for the patients received hip arthroplasty. Although there was lack of evidence to prove the relationship between propofol and incidence of POD, the results from one previous study indicated that intraoperative deep sedation with propofol was related to a higher incidence of POD.8 Recently, several studies recommend another sedative drug, dexmedetomidine, be potentially helped reduce occurrence of POD.9, 10 For the patients received hip arthroplasty, we hypothesized that intraoperative sedation with dexmedetomidine, as a supplement to RA, would be associated with a lower incidence of POD and positive postoperative outcomes compared to intraoperative sedation with propofol.


In this study, a prospective randomized controlled trial was conducted to compare the influence of two supplemental intraoperative sedative drugs (dexmedetomidine and propofol) to peripheral nerve block (lumbosacral plexus plus T12 paravertebral block) on the incidence of POD in elderly patients undergoing hip arthroplasty. Also the influence of these two sedative drugs on the incidence of early POCD and the short-term recovery of patients was investigated. METHODS Ethical approval and patient eligibility criteria Ethical approval for this study (PJ2015-07-12) was provided by the Ethical Committee of The First Affiliated Hospital of Anhui Medical University (Hefei, Anhui Province, China) on August 7, 2015. Patients or their relatives provided written informed consent to be included in this study. The patients included in this study were 65 years or older, were undergoing total hip arthroplasty, and were classified as American Society of Anesthesiologists (ASA) physical health class I–IV. For patients received anticoagulants, clopidogrel were required to replace by subcutaneous low molecular heparin for 7 days before surgery. And lumbosacral plexus and T12 paravertebral block was performed 24 hours after the last use of therapeutic dose of low molecular heparin and 12 hours after the last use of prophylactic dose of low molecular heparin. Low molecular heparin was reused 24 hours after surgery. For patients who used aspirin, there was no contraindication to receive lumbosacral plexus and T12 paravertebral block. Also the international normalized ration of prothrombin time (PT-INR) of patients was required less than 1.4 and the platelet count was required more than 80×109. Exclusion criteria included: contraindications to lumbosacral plexus and T12 paravertebral block (i.e., coagulopathy, infection at puncture site, and refusal of lumbosacral plexus and T12 paravertebral block),


patients with mental or language barriers, patients who had been anesthetized within the past 30 days, severe congestive heart failure (New York Heart Association, class IV) and/or severe chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease Guidelines, stages III–IV), sick sinus syndrome, severe sinus bradycardia (< 50 beats per min), and second or greater atrioventricular block without pacemaker. In addition, patients exhibiting cognitive impairment (i.e., a Mini-Mental State Examination (MMSE) score < 24) and/or preoperative delirium (i.e., positive Confusion Assessment Method (CAM) result) were excluded. As described in one previous study, the MMSE score was determined from these following aspects: orientation, registration, attention and calculation, recall and language.11 As described in another study, the diagnosis of delirium by CAM was base on four following features: acute onset and fluctuating course, inattention, disorganized thinking, altered level of consciousness.12 Study protocol Information regarding demography, medications, and comorbidities were collected for each patient prior to surgery. An Inouye risk assessment was completed for each patient to determine risk of delirium.13 All of the patients were scheduled to receive peripheral nerve block, while computer-generated assignments determined whether supplemental sedation would be induced with propofol (Group P) or dexmedetomidine (Group D). The following vital signs were established upon arrival into the operation room and were subsequently monitored: invasive arterial pressure, pulse oximetry, and 5-lead electrocardiography. In addition, bispectral index (BIS) monitoring (Vista, Aspect Medical System Inc., USA) was used to determine the depth of sedation for all of the patients. Oxygen supplementation was applied to all of the patients through a non-rebreathing mask before


patients were sedated. For patients in Group P, sedation was achieved with a target-controlled infusion of propofol, and the effect site concentration was set to 0.8-1.0 μg/ml. For patients in Group D, sedation were achieved with a bolus of dexmedetomidine at 0.8-1.0 μg/kg that was administered over 15–20 min and this was followed by an infusion of dexmedetomidine at 0.10.5 μg·kg-1·h-1. One anesthesiologist in our department assessed the depth of sedation every 10 minutes after sedative drugs infused, and the depth of sedation was maintained to achieve observer’s assessment of alertness/sedation (OAA/S) score 3 or 4 by adjusting the infusion rates.14 Peripheral nerve block was performed 30 min after the infusion of sedative drugs. Patients were placed in a lateral position with the operated side facing up. The limb to be blocked was flexed at both the hip and knee. An electrically isolated 12-cm 22G needle (Stimuplex D, B. Braun Medical, Germany) and peripheral nerve stimulator (Stimuplex HNS 12, B. Braun Medical) were used to perform lumbosacral plexus blocking. As described in previous study,15 the point of lumbar plexus puncture was the intersection between a vertical line parallel to the spinous processes and passing through the posterior superior iliac spine and a transverse line passing the cephalad borders of both iliac crests. After a local infiltration performed by 1% lidocaine, the needle was inserted directly to reach the transverse process of the fourth lumbar vertebra. Then the needle was redirected caudally and advanced 1–2 cm until the lumbar plexus was stimulated. To identify the puncture point of the sacral plexus,16 a line was drawn between the posterior superior iliac spine and the lowest point of the ischial tuberosity. The puncture point was made 6 cm inferior to the posterior superior iliac spine. After a local infiltration performed by 1% lidocaine, the needle was inserted perpendicularly to the skin and advanced until the sacral plexus was stimulated. The lumbar plexus and sacral plexus were identified using the


motor response of the femoral quadriceps and the gluteus maximus plus gastrocnemius, respectively. Stimulation was initially assessed at an intensity of 1.5 mA for duration of 50 μs and with a frequency of 2 Hz. After measuring the motor response of the target muscles, the final postion of the needle was based on the best response to stimulation between 0.5 mA and 0.35 mA to provide an effective block and prevent nerve injury. 25 ml of 0.4% ropivacaine was administered for lumbar plexus blocking, and 15 ml of 0.4% ropivacaine was given for sacral plexus blocking. After lumbosacral plexus block completed, an ultrasound-guided T12 paravertebral block was performed with an Edge ultrasound medicine (FUJIFILM SonoSite, inc. Bothell, USA) and a 2 to 5 MHz convex transducer (FUJIFILM SonoSite, inc. Bothell, USA). According to previous study,7 the transducer was placed on the patient in a transverse and partial oblique position to the vertebral column, parallel to the rib at the T12-L1 intervertebral space, to obtain a view of the lateral apex of the thoracic paravertebral space (TPVS)(Fig.1A). After a local infiltration performed by 1% lidocaine, a 9-cm 22G needle (KDL medical company, Zhejiang, China) was inserted and advanced in plane with the transducer, in a lateral-to-medial direction. After the needle reach the TPVS, 10 ml of 0.4% ropivacaine was injected (Fig.1B). Additional confirmation of successful block was provided if the patients displayed no pain from the pinprick test before surgery. Surgeries were started 20 min after blocking was performed. If patients exhibited any indications of pain or discomfort from skin incisions or any of the surgical procedures, the patients were excluded from the study and GA was immediately administered. Spontaneous respiration of each patient was maintained during surgery. A restrictive infusion strategy (i.e., 3–4 ml/kg/h) was applied to all of the patients. Intraoperative hypotension was defined as a decrease > 30% in systolic blood pressure from preoperative values and/or systolic blood pressure < 90 mmHg. If observed, these conditions were immediately


treated with an infusion of phenylephrine or ephedrine by bolus depending on the patient’s heart rate and anesthesiologist’s preference. Intraoperative bradycardia was defined as heart rate (HR) < 60 beats per minute. As elderly patient were included in this study, the bradycardia was treated with ephedrine by bolus when HR < 55 beats per minute. A group of experienced arthroplasty surgeons performed all of the operations and a posterior approach was used each time. Consumption of propofol, dexmedetomidine, sufentanil, phenylephrine, and ephedrine was recorded. Intraoperative HR, mean artery pressure (MAP), and BIS values were also recorded at different time intervals. Upon completion of surgery, the infusion of sedative drug for each group was discontinued. All of the patients were transferred to a post-anesthesia unit for recovery until they received a Steward score of at least 4 which was assessed from following aspects: consciousness, airway and movement.17 Patient controlled analgesia (PCA) was available post-surgery and it consisted of sufentanil (2.5 μg/kg) and flurbiprofen axetil (150 mg) diluted in saline to 150 mL. Both the loading dose and the first bolus had volumes of 3 ml. No background infusion was included and the lockout time was 15 min. Consumption of PCA boluses and postoperative analgesics were both recorded. The primary endpoint was the incidence of POD, which was assessed using CAM from the first postoperative day to the third postoperative day. Early POCD was assessed on the third and seventh postoperative days according to scores from the MMSE. Postoperative pain was assessed on the first and third postoperative days according to visual analog scale (VAS) scores. Two trained individuals in our department conducted the POD and POCD assessments, respectively. They were also blinded to this study. The length of stay and time of ambulation after surgery were recorded. Also, postoperative complications within 30 days of surgery were recorded.


Sample size and statistical Analyses To achieve a power of 0.9 at a level of significance of 0.05 for analyzing incidence of POD as the primary endpoint, the following considerations were included. First, a failure rate of nearly 15% was assumed for peripheral nerve block. Second, in previous studies, the incidence of POD was reported to be 19% in elderly patients that received light sedation by propofol8 and 3% for patients receiving dexmedetomidine.18 Therefore, the prevalence of POD following administration of dexmedetomidine for the elderly patients of the present cohort was estimated to be double the rate reported for younger patients.10 As a result, there were 148 patients included in Group P and 148 patients included in Group D. Statistical analyses were performed by using SPSS 21.0 software (SPSS, IBM, USA). Numerical values are presented as the mean ± standard deviation. Continuous normally distributed data (e.g. time of ambulation and the length of stay after surgery) were analyzed using a two-tailed unpaired t test. Hemodynamic and BIS data were analyzed using two-way analysis of variance (ANOVA) with Bonferroni correction for multiple comparisons as significant F ratios were obtained. The Mann-Whitney U-test was used to analyses nonparametric data (e.g. MMSE scores and difference between the preoperative and postoperative MMSE scores). Frequency data (e.g. incidence of POD) were analyzed using the chi-square test for differences in probabilities of a 2×2 contingency table. Odds ratio and confidence intervals (CIs) for proportions were calculated at 95%. A P-value of less than 0.05 was considered to indicate a statistically significant difference. RESULTS A total of 392 patients were assessed for eligibility for this study between June 2016 and June


2017. Fifty-six patients were excluded based on the inclusion criteria established for this study or because they declined to participate. The remaining 336 patients were randomly assigned to Group D or Group P. Among these patients, data for 34 patients were not analyzed due to failed peripheral nerve block (n = 23) or cancellation of surgery (n = 11). However, the success rate of lumbosacral plexus plus T12 paravertebral block for the patients that underwent surgery was 93% (302/325). After 6 patients were lost to follow-up, there were 296 patients that were analyzed, including 148 patients in each group (Fig. 2). There were no significant differences in gender, age, body mass index (BMI), or ASA physical status scores between Group D and Group P. There were also no differences in preoperative MMSE scores, medication intake, incidence of comorbidities, and risk of delirium (according to the Inouye risk assessment) between the two groups (Table 1). Regarding the intraoperative data, there were no significant differences in the duration of surgery or in the consumption of sufentanil, phenylephrine, and ephedrine between the two groups. The consumption of propofol in Group P and dexmedetomidine in Group D were 262 ± 94 mg and 105 ± 43 μg, respectively. As shown in Figure 3, there were no differences in intraoperative HR, MAP, and BIS among the various time intervals. As shown in Table 3, patients in Group D were out of bed earlier than patients in Group P (mean ± SD: 1.7 ± 0.3 days in propofol group versus 1.4 ± 0.2 days in dexmedetomidine group, P = 0.026) Also, patients in Group D obtained a shorter length of stay after surgery than patients in Group P (mean ± SD: 6.8 ± 2.0 days in Group P versus 6.3 ± 1.6 days in Group D, P = 0.021). Between Group P and Group D, there were no significant differences in boluses of PCA (P = 0.627) and postoperative consumption of analgesics (all P > 0.99). The VAS scores in two groups were similar in the first postoperative day (P = 0.156) and third postoperative day (P =


0.306). Also as shown in Table 3, compared to Group P, there were a smaller proportion of patients in Group D exhibited POD (odds ratio [OR]: 0.41; 95% CI: 0.20-0.88; P = 0.03). Patients in Group D had higher MMSE scores than patients in Group P on both the third postoperative day (mean ± SD: 25.2 ± 3.3 in Group D versus 21.3 ± 4.0 in Group P, P < 0.001) and on the seventh (mean ± SD: 24.9 ± 3.6 in Group D versus 23.1 ± 3.2 in Group P, P < 0.001). The difference between the preoperative and postoperative MMSE scores was less pronounced in Group D than Group P (P < 0.001 of the third postoperative day and P = 0.025 of the seventh postoperative day). DISCUSSION In this study, we found different recovery outcomes between patients received two different sedative drugs as the supplement to peripheral nerve block. Sedation with dexmedetomidine was associated with a lower incidence of POD and early POCD compared to sedation with propofol. Sedation with dexmedetomidine also facilitated patients to be out of bed and discharged early after surgery. POD is a common postoperative complication within elderly patients. As described by others, this fluctuating mental status was most commonly found between postoperative days 1 and 3.19 As mentioned above, the occurrence of POD in elderly patients can lead to early POCD and numerous negative effects on patients’ recovery and patients’ survival in some cases. Results of our previous study also indicated the increasing incidence of POD was related to an increasing incidence of early POCD, which was detected on the 3rd and 7th postoperative day.20 So in this study, for POD, the primary endpoint, we recorded it daily from the first postoperative day to the third postoperative day. For the incidence of POCD, we recorded the MMSE on the 3rd and 7th


postoperative day. There have been increasing concerns regarding the relationship between anesthetic technique and POD. For example, perioperative use of opioids is recognized to be an important risk for POD.21 With the application of RA, this risk can be reduced or avoided. It continues to be debated whether RA reduces the incidence of POD compared with GA.22 With RA, intraoperative sedative level or the type of drug applied can represent potential risk factors for POD.8 In our previous study, patients received RA were sedated by propofol with different sedative level during operation, the result of our study indicated deep sedation was related to higher incidence of POD and early POCD.20 Although there is no direct evidence that an infusion of propofol contributes to the occurrence of POD, we have to realize that the deep sedation was accomplished by larger amount of propofol in our previous study, and also animal studies have indicated that propofol may have neurotoxic properties.23 More recently, another sedative drug, dexmedetomidine, was reported to prevent POD in elderly patients following its use in intensive care units.9, 10 Possible mechanisms included improved quality of sleep and an inhibitory effect on inflammation24, 25 In the present study, an intraoperative infusion of propofol or dexmedetomidine as a supplement to peripheral nerve block resulted in a consistent sedation level in both groups. However, the incidence rates of POD and early POCD in the patients that received dexmedetomidine were lower compared with the rates for the patients that received propofol. The patients that received dexmedetomidine were also out of bed sooner, had a quicker return to functional training, and had a shorter hospitalization stay following surgery compared to the patients that received propofol. These results are inconsistent with those of a recent study where intraoperative infusions of dexmedetomidine did not prevent the occurrence of POD and POCD in elderly patients who were undergoing major elective noncardiac surgery.26 An


important difference between this study and our present study is that there were no other general anesthetics used in our study. Additionally, we only included patients received hip surgery. Results of our study indicated that as a supplement to RA, intraoperative sedation with dexmedetomidine has more advantages than propofol to reduce the incidence of POD and early POCD, and facilitates a quicker return to functional training and probably shorten length of stay in hospital for elderly patients receiving hip surgeries. Unstable hemodynamics have also been associated with the occurrence of POD.27 A sedative dose of dexmedetomidine, a highly selective α2-adrenoreceptor agonist, has been reported to cause hypotension and bradycardia.28, 29 In the present study, to reach a sedation level which satisfies the requirement for an invasive procedure involving puncture and surgery, a larger dose of dexmedetomidine was applied (0.8–1.0 μg/kg per bolus and 0.1–0.5 μg/kg/h for subsequent infusions) compared with the dose reported in another study.9 There were no differences in the hemodynamics for Groups D and P, or in the application of vasoactive agents. Therefore, we can exclude the possibility that hemodynamics influence the incidence of POD and other outcomes in the present study. In our study, lumbosacral plexus plus T12 paravertebral block was used as the anesthesia method, rather than neuraxial anesthesia, which is the most common method performed in patients receiving hip surgeries.30, 31 In our clinical anesthetic work, lumbosacral plexus plus T12 paravertebral block was routinely used due to large proportion of patients with ankylosing spondylitis. For these patients, the application of neuraxial anesthesia was limited because of the difficult puncture. As reported by Dr Ke and his colleagues, in four cases of hip replacement for patients with ankylosing spondylitis, T12 paravertebral block plus lumbosacral plexus block could fully meet the need of surgical analgesia requirement.7 Also, a prospective study reported


that lumbosacral plexus block can satisfy the requirement of hip surgeries, and have less influence on hemodynamics compared with spinal anesthesia.32 Most important, with the guidance of ultrasound and nerve stimulator, the safety and effectiveness of this combined blocking was guaranteed. In the present study, we reported a high success rate (93%) of this combined blocking. There were several limitations associated with this study. First, the present results do not completely exclude the possibility that dexmedetomidine prevents the occurrence of POD and early POCD. Ideally, future studies should include a group of patients that only receive peripheral nerve block without any sedation to address this consideration. However, there is an ethical consideration for submitting patients to a surgery during which they may be anxious and/or experience postural discomfort. Secondly, patients with preoperative cognitive impairment were excluded from this study. This condition may restrict the generalizability of the results obtained to patients with preoperative dementia. Moreover, preoperative dementia is considered a major risk factor for the occurrence of POD.33, 34 However, without the probable development of POD in the patients of our cohort, the benefits of our intervention could be more clearly observed. Indeed, based on the results of the present study, a prospective multicenter randomized controlled trial should be conducted to confirm whether the benefits of dexmedetomidine observed in the present study would be extended to patients with preoperative dementia. CONCLUSIONS In the present study, lumbosacral plexus plus T12 paravertebral block was applied to elderly patients undergoing total hip arthroplasty. Supplementation of this block with sedation provided by propofol or dexmedetomidine resulted in successful surgeries for > 90% of the present cohort.


The most important finding of our study is intraoperative sedation with dexmedetomidine was associated with a lower incidence of POD, which may have benefits on reducing the incidence of early postoperative cognitive dysfunction and offering a better short-term recovery for elderly patients receiving hip arthroplasty. Based on these findings, we recommend that lumbosacral plexus plus T12 paravertebral block and sedation with dexmedetomidine represent a promising anesthetic regimen for elderly patients undergoing hip surgeries, especially patients who are constrained to general and neuraxial anesthesia. ACKNOWLEDGEMENTS This work was supported by National Natural Science Foundation of China (Grant number: 81171031 and 81571039)


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26. Deiner S, Luo X, Lin HM, et al. Intraoperative Infusion of Dexmedetomidine for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective Noncardiac Surgery: A Randomized Clinical Trial. JAMA Surg. 2017; 152(8): e171505. 27. Yang L, Sun DF, Han J, Liu R, Wang LJ, Zhang ZZ. Effects of Intraoperative Hemodynamics on Incidence of Postoperative Delirium in Elderly Patients: A Retrospective Study. Med Sci Monit. 2016; 22: 1093-100. 28. Pandharipande PP, Pun BT, Herr DL, et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA. 2007; 298(22): 2644-2653. 29. Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009; 301(5): 489-499. 30. Basques BA, Toy JO, Bohl DD, Golinvaux NS, Grauer JN. General compared with spinal anesthesia for total hip arthroplasty. J Bone Joint Surg Am. 2015; 97(6): 455-461. 31. Hunt LP, Ben-Shlomo Y, Clark EM, et al. 90-day mortality after 409,096 total hip replacements for osteoarthritis, from the National Joint Registry for England and Wales: a retrospective analysis. Lancet. 2013; 382(9898): 1097-1104. 32. Visme V, Picart F, Jouan RL, Legrand A, Savry C, Morin V. Combined lumbar and sacral plexus block compared with plain bupivacaine spinal anesthesia for hip fractures in the elderly. Region Anesth Pain M. 2000; 25(2): 158-162. 33. Marcantonio ER, Flacker JM, Michaels M, Resnick NM. Delirium is independently associated with poor functional recovery after hip fracture. J Am Geriatr Soc. 2000; 48(6): 618-624. 34. Edlund A, Lundström M, Brännström B, Bucht G, Gustafson Y. Delirium before and after operation for femoral neck fracture. J Am Geriatr Soc. 2001; 49(10): 1335-1340.


Figure Legends Figure 1: Ultrasonography of paravertebral block. Ultrasonography of the T12 thoracic paravertebral space prior to (A) and following (B) the injection of regional anesthetic. SP = spinous process; TP = transverse process; TPVS = thoracic paravertebral space. Figure 2: Flow chart of patient selection. Patients in Group P underwent peripheral nerve block plus propofol sedation; patients in Group D underwent peripheral nerve block plus dexmedetomidine sedation. Figure 3: Intraoperative BIS values and hemodynamics. BIS = bispectral index; HR = heart rate; MAP = mean artery pressure.


TABLE 1. Demographic Characteristics of the Participating Patientsa Characteristic

Group P

Group D

P value

Gender (n) male/female

71/77

64/84

0.484

Age (y), mean ± SD

74±6

76±7

0.065

Body mass index (BMI), mean ± SD

24.9±4.4

23.7±6.2

0.546

3 (2–3)

3 (2–3)

0.899

25.7±1.7

26.2±2.1

0.105

Benzodiazepine use

18 (12)

24 (16)

0.405

Opioid use

37 (25)

44 (30)

0.434

Hypertension

92 (62)

84(57)

0.407

Coronary disease

29 (20)

17 (11)

0.077

Arrhythmia

66 (45)

56 (39)

0.288

Chronic obstructive pulmonary disease

26 (18)

39 (26)

0.092

Cerebrovascular disease

21 (14)

14 (9)

0.280

ASA physical status score, median (lower-upper quartile) Mini-mental state examination score, mean ± SD

Comorbidities:


Inouye risk, median (lower-upper quartile) (range, 1- 2 (1–2)

2 (2–2)

0.694

3)b a

Data are No. (percentage) unless indicated otherwise.

b

For Inouye risk, 1 indicates low risk (0 points); 2 indicates intermediate risk (1–2 points);

and 3 indicates high risk (3–4 points), in which 1 point is assigned for each of the 4 risk factors (visual impairment, severe illness, cognitive impairment, high blood urea nitrogencreatinine ratio).


TABLE 2. Intraoperative Data for the experimental Groupsa Group P

Group D

P value

Duration of surgery (min), mean ± SD

79.5±20.6

75.9±26.7

0.101

Propofol dose (mg), mean ± SD

262±94

-

-

Dexmedetomidine dose (μg), mean ± SD

-

105±43

-

Sufentanil dose (μg), mean ± SD

11.7±3.4

11.0±5.2

0.082

Phenylephrine dose (μg), mean ± SD

51.7±22.9

46.4±27.3

0.192

Ephedrine dose (mg), mean ± SD

9.4±3.8

10.6±4.5

0.524


TABLE 3. Postoperative Data for the Experimental Groups

Group P

Group D

P value

Postoperative deliriuma

24 (16)

11 (7)

0.030

Time of ambulationb (d), mean ± SD

1.7±0.3

1.4±0.2

0.026

The length of stay after surgery (d), mean ± SD

6.8±2.0

6.3±1.6

0.021

Boluses of PCAd, mean ± SD

6±2

5±3

0.627

Sufentanil (μg)

16.3±8.1

17.5±8.9

>0.99

Flurbiprofen axetil (mg)

12.6±5.1

13.2±6.4

>0.99

Day 1

1.7±1.2

1.9±1.3

0.156

Day 3

1.8±0.8

2.1±1.4

0.306

Postoperative analgesic dose, mean ± SD

Postoperative VASe score, mean ± SD


Postoperative MMSEf score, mean ± SD

Day 3

21.3±4.0

25.2±3.3