Yılmaz F 1 Günüşen İ 1 Çertuğ A 1 Önen Sertöz Ö 2. Summary - PDF

Araştırma Makalesi / Research Paper Ege Tıp Dergisi / Ege Journal of Medicine 51(1): 1-8, 2012 The effect of dexmedetomidine on cognitive function and anxiety in middle-ear surgery Orta kulak cerrahisinde

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Araştırma Makalesi / Research Paper Ege Tıp Dergisi / Ege Journal of Medicine 51(1): 1-8, 2012 The effect of dexmedetomidine on cognitive function and anxiety in middle-ear surgery Orta kulak cerrahisinde uygulanan deksmedetomidinin kognitif fonksiyonlar ve anksiyete üzerine etkisi Yılmaz F 1 Günüşen İ 1 Çertuğ A 1 Önen Sertöz Ö 2 1 Ege Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, İzmir, Türkiye 2 Ege Üniversitesi Tıp Fakültesi, Psikiyatri Anabilim Dalı, İzmir, Türkiye Summary Aim: Controlled hypotension has been used commonly during surgical procedures to reduce intraoperative hemorrhage. However, it can be detrimental to cognitive functions. This study is a prospective trial conducted to compare the effects of remifentanil alone and dexmedetomidine supplemented with remifentanil infusions on cognitive function and anxiety. Materials and Methods: Forty patients scheduled for tympanoplasty were allocated randomly into groups to receive either remifentanil (1μg kg -1 loading; maintenance, µg kg -1 min -1 ) or dexmedetomidine combined with remifentanil infusion (1 μg kg -1 dexmedetomidine loading; maintenance, 0.5 μg kg -1 h -1 dexmedetomidine and µg kg -1 min -1 remifentanil). Hemodynamic changes, opioid requirement, bleeding, recovery time, cognitive functions and anxiety scores were recorded. Results: Dexmedetomidine combined with remifentanil was found to have the same effect as remifentanil alone on hemodynamics. The remifentanil group was associated with significantly shorter recovery time. A mini-mental status test at 30 and 120 min and the Trieger dot test at 30 and 60 min in the remifentanil group were better than the other group whereas the Digit symbol substitution test and anxiety scores were similar in both postoperatively. The patients in the dexmedetomidine group had only lower anxiety scores postoperatively according to baseline values. Conclusion: Remifentanil was more advantageous in middle ear surgery as it was associated with a shorter recovery time and earlier recovery of cognitive functions compared with the dexmedetomidine group. Key Words: Controlled hypotension, remifentanil, dexmedetomidine, cognitive function, anxiety. Özet Amaç: Kontrollü hipotansiyon, intraoperatif kanamayı azaltmak amacıyla cerrahi operasyonlar sırasında sıklıkla kullanılır. Ancak, kontrollü hipotansiyon kognitif fonksiyonlar üzerine zararlı olabilir. Bu prospektif çalışma, sadece remifentanil infüzyonu ile deksmedetomidin ve remifentanilin birlikte infüzyonlarının kognitif fonksiyonlar ve anksiyete üzerine etkilerini karşılaştırmak amacıyla yapıldı. Gereç ve Yöntem: Timpanoplasti uygulanacak 40 hasta, remifentanil (1μg kg-1 yükleme; µg kg-1 dk-1 infüzyon) ya da deksmedetomidin ile remifentanil infüzyonlarının birlikte uygulandığı (1 μg kg-1 deksmedetomidin yükleme ve bunu takiben 0.5 μg kg-1 sa-1 deksmedetomidin ve µg kg-1 dk-1 remifentanil infüzyonu) 2 gruptan birisine randomize edildi. Hastaların operasyon süresince hemodinamik değişimleri, opiyat gereksinimi, kanama, operasyon sonrası derlenme zamanı, kognitif fonksiyonlar ve anksiyete skorları kaydedildi. Bulgular: Hemodinamik değişimler açısından deksmedetomidine ile remifentanil infüzyonu uygulanan grup ile sadece remifentanil infüzyonu uygulanan grupların benzer etkiye sahip oldukları bulundu. Derlenme zamanı remifentanil grubunda belirgin olarak kısaydı. Yine bu grup hastalarda operasyon sonrası 30 ve 120.dk da Minimental test, 30 ve 60.dk da ise Trieger dot testi sonuçları daha iyi bulunurken Digit symbol substitution testi ve anksiyete skorları açısından her iki grupta benzer sonuçlar elde edildi. Deksmedetomidin uygulanan hastaların anksiyete skorları sadece bazal değerlere göre daha düşüktü. Yazışma Adresi: İlkben GÜNÜŞEN Ege Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, İzmir, Türkiye Makalenin Geliş Tarihi: Kabul Tarihi: Sonuç: Orta kulak cerrahisinde, deksmedetomidin ile karşılaştırıldığında kısa derlenme zamanı ve kognitif fonksiyonların erken düzelmesi nedeniyle remifentanil daha avantajlı bulundu. Anahtar Sözcükler: Kontrollü hipotansiyon, remifentanil, deksmedetomidin, kognitif fonksiyonlar, anksiyete. Introduction Controlled hypotension, which reduces bleeding, has been used for a long time to obtain better exposure during operations performed under microscope (1, 2). It is defined as a reduction of the systolic blood pressure to mmhg, a reduction of mean arterial pressure (MAP) to mmhg or a 30% reduction of baseline MAP (3). Several pharmacological agents, including beta-adrenergic receptor antagonists, calcium channel blockers, volatile anesthetics, esmolol, propofol, remifentanil and dexmedetomidine are used for controlled hypotension (1-4). Particularly, dexmedetomidine and remifentanil are rapidly acting drugs with a short duration of action that can be titrated to obtain a moment-tomoment control of arterial pressure (1). Hypotension may cause cognitive deficits, and such changes have been used to investigate the role of cerebral perfusion (5). Cognitive functions are also affected after general anesthesia to a varying degree. The brain as a whole is not affected to the same degree by anesthetics, but those specific brain regions (and particular cognitive processes mediated by these regions) are more sensitive to anesthesia and sedation than others (6). Delayed physical and emotional rehabilitation may postpone hospital discharge and return to work (7). In ambulatory surgery, it is important to use drugs with short onset and duration of effect, resulting in quick recovery and the possibility of earlier discharge from the day surgical unit (8). Moreover, patients who await surgery usually suffer from varying degrees of fear and anxiety. This anxiety is influenced by the uncertainty of the impending anesthetic and surgical procedures, past experience, patient s personality, intra and postoperative pain. It also may adversely influence anesthetic induction and patient recovery, as well as decrease patient satisfaction with the perioperative experience (9). In this study, we also investigated patients anxiety levels as well as cognitive and psychomotor functions since dexmedetomidine has an anxiety relieving effect. In the literature, there are few studies in which dexmedetomidine is compared to remifentanil for controlled hypotension and the effects of these drugs on cognitive function are not evaluated (1,10,11). In our clinic, we routinely use remifentanil for providing hypotension during middle-ear surgery in order to benefit both from its analgesic effect and also from the middle ear blood flow decrease (3). While planning this study, 2 we determined that in studies using dexmedetomidine infusion for controlled hypotension in order to reach a target MAP level, the level was higher than ours (2), this drug was used in higher doses (1) or required additional opioid (2, 11). Therefore, our study protocol was intended to give the dexmedetomidine applied group easily titrated remifentanil infusion instead of bolus dosing for better hemodynamic stability. This study tested the hypothesis of whether dexmedetomine or remifentanil, used as adjunctions for controlled hypotension, can affect cognitive function recovery characteristic and anxiety postoperatively. Materials and Methods After the ethics committee approval and informed consent, 40 healthy high-school-graduate male and female ASA physical status I and II patients, aged years, scheduled to undergo elective tympanoplasty were included in this study. Exclusion criteria for potential subjects were a history of a significant cardiac, pulmonary, hepatic or renal disease, chronic drug or alcohol abuse, disabling neuropsychiatric disorders, morbid obesity, pregnancy, hypersensitivity to anesthetic drugs, hypertension (systolic blood pressure 150 mmhg) and bradycardia (heart rate 50 beats min -1 ). The day before surgery, psychomotor state and cognitive function were evaluated with MMST (Mini- Mental State Test), DSST (Digit symbol substitution Test) and TDT (Trieger Dot Test). In addition, State-Trait Anxiety Inventory scale (STAI) was performed to measure the level of anxiety (12,13). The MMST is a screening test to quantitatively assess cognitive deterioration by questions on orientation, memory, attention, verbal recall and learning, visual-constructive ability (4). The DSST is the most sensitive of the tests for residual cortical depression by anesthetics, in particular, impairment of information processing performance and the ability to concentrate. The DSST is a timed test that presents the subject with a chart of eight rows of digits in random sequence. A key of the nine numerical digits and their corresponding symbols is provided. The subject s task is to replace the digit with its corresponding symbol. The number of correct substitutions within a 60s period is tallied. In the TDT, patients are asked to connect dots within 60s; missed dots and the distance line-dot (mm) are noted (13, 14). The STAI consists of 20 questions that determine how the respondents feel right now. The score may vary from a minimum of 20 to a maximum of 80 (12). Ege Tıp Dergisi / Ege Journal of Medicine Premedication was not prescribed to any patients. Prior to being transferred to the operation room, baseline MAP and heart rate (HR) were calculated as the mean of the three recordings in the ward. On arrival in the operating room, the patients heart rate, blood pressure (systolic, diastolic and mean arterial blood pressure), and oxygen saturation were monitored by electrocardiography (ECG), non-invasive blood pressure monitor and pulse oximetry (Datex-Ohmeda, Helsinki, Finland), respectively. Using a computerized random generation program, patients were randomized to receive either remifentanil (, n=20) or dexmedetomidine combined with remifentanil (D, n=20). Lactated Ringer s solution, with a rate of 10 ml kg -1 h -1, was started through an 18-gauge (G) intravenous (i.v.) cannula which was inserted in the right hand. The patients in received an infusion of 1 μg kg -1 over 1 min before anesthesia induction followed by µg kg - 1 min -1 continuous infusion throughout the operation. D received a loading dose of dexmedetomidine 1 μg kg -1 over 10 min before anesthesia induction followed by a continuous infusion at a rate of 0.5 μg kg -1 hr -1 dexmedetomidine and μg kg -1 min -1 remifentanil. Anesthesia was induced with propofol 2 mg kg -1 and atropine 0.01 mg kg -1, and endotracheal intubation was facilitated with vecuronium 0.1 mg kg -1 and then maintained in both groups with sevoflurane at MAC (end-tidal) in 50% oxygen/air. Patients were mechanically ventilated, adjusted to provide an end-tidal CO 2 ( ETCO 2) pressure of mmhg, while the body temperatures of the patients were maintained at C. After anesthesia induction, arterial blood pressures of all the patients were continuously monitored invasively throughout the surgery due to controlled hypotension via a 20 G catheter inserted into the radial artery of the left hand. Lactate concentration was measured by arterial blood gas analyzer after induction, at 60 min and at the end of surgery. The remifentanil infusion rates were then titrated to maintain mean arterial pressure of 55 to 65 mmhg during operation in both groups. Sevoflurane concentration and dexmedetomidine infusion rate were kept unchanged throughout the course. In both groups, signs of inadequate anesthesia (increase in MAP or HR 20%) were treated by increasing remifentanil infusion rate. Esmolol (bolus, i.v) was planned to be administered if these target limits could not be achieved. A heart rate of less than 50 beats min -1 was treated by decreasing the dosage of remifentanil and administering atropine of 10 μg kg -1. If necessary, while a MAP of less than 55 mmhg was treated with intravenous fluids, decreasing the remifentanil infusion and administering ephedrine 5 mg intravenously. Patient and surgical characteristics, remifentanil and dexmedetomidine consumption were recorded at the end of surgery. HR and MAP were measured continually during surgery but were recorded before and after intubation and at 10-min intervals. The amount of bleeding during the operation was assessed by a 6-point scale (0=no bleeding, 1=mild bleeding-no need of blood aspiration, 2=mild bleeding-occasional aspiration necessary. Clear surgical field, 3=moderate bleedingfrequent aspiration necessary. Bleeding closes surgical field a few seconds following aspiration, 4=moderate bleeding-frequent aspiration necessary. Bleeding closes surgical field right after aspiration, 5= excessive bleeding-continuous aspiration necessary. Bleeding appears faster than aspiration. Surgical field is closed and surgery is not possible). Scores 2 were considered to be an optimal surgical condition (4). Dexmedetomidine and remifentanil infusions were stopped 5-10 minutes before the end of surgery. Sevoflurane was discontinued before the completion of surgical suturing and patients were ventilated with 100% oxygen at 5 L min -1. Following a spontaneous recovery, a combination of atropine 0.02 mg kg -1 and neostigmine 0.04 mg kg -1 was administered i.v. to reverse the neuromuscular block. Recovery time was evaluated with the Aldrete score (a scale of 0-10) in the operating room. Patients who scored or =9 were discharged from the operating room to post-anesthesia care unit (PACU) (15). The patients were monitored in the PACU for 4 hours. All the patients were given 75 mg of intramuscular diclophenac sodium to serve as an analgesic drug. If the visual analogue pain score (VAS, mm) was greater than 40 mm, 50 mg of i.v. meperidine was administered. Patients suffering from nausea or vomiting were treated with 4 mg of i.v. ondansetron. MMS, DSST, TDT and STAI were repeated in the post anesthesia care unit (PACU) at 30 th, 60 th and 120 th min after discontinuation of anesthesia. Before and after surgery, all of the tests related to cognitive and psychomotor performance and level of anxiety were performed by an anesthesiologist. Statistical analysis Statistical analyses were performed with the SPSS (SPSS for Windows Release 13.0) Statistical Package and data were shown as a mean and standard deviation (SD), or percentage. Age, weight, height, duration of anesthesia and surgery, time to complete recovery from anesthesia, lactate concentration in arterial blood, cognitive functions and anxiety scores were compared using the Student s t-test. The amount of blood, sex and bradycardia were compared in two groups using Chi- Square test and Fisher s exact test. Intraoperative opioid Cilt 51 Sayı 1 Mart 2012 / Volume 51 Issue: 1 March Heart rate (beats/min) consumption was compared using the Mann- Whitney U test. MAP and HR were compared using repeatedmeasures analysis of variance. All post hoc comparisons were performed using Bonferroni. P 0.05 was considered statistically significant p=0.016 p=0.004 *ƒ *ƒ p=0.008 D Results There was no significant difference between the groups regarding age, weight, height and gender. Durations of anesthesia and operation were similar in both groups (Table-1). patients received a total of ±357 μg of remifentanil, whereas those in Group RD received 269.7±243.7 μg of remifentanil and 131.3±31.1μg of dexmedetomidine Baseline After intubation *ƒ ƒ ƒ Time (min) ƒ ƒ ƒ ƒ ƒ Table-1. Demographic data, duration of anesthesia and surgery D (n:20) (n:20) P values Age (years) 36.5± ± Weight (kg) 70.8± ± Height (cm) 167.5± ± Duration of anesthesia (min) Duration of surgery (min) 109.2± ± ± ± Gender (M/F) 11/9 12/8 0.7 Data are mean ±SD, M:male, F:female, RD:dexmedetomidine plus remifentanil, R:remifentanil, no statistically differences between groups HR and MAP are presented in (Figure-1). Both HR and MAP were similar in baseline measurements between groups. In an intergroup comparison, HR was significantly lower in D compared with before intubation, after intubation and at 10 th min. One patient in D received atropine because of bradycardia. MAP was lower in D than in Group R only before intubation while it was higher at 70 th and 80 th min (p 0.05). No patients required ephedrine. In an intragroup comparison, HR and MAP significantly decreased in both groups at all time measurements when compared with baseline values, except for HR in after and before intubation and for MAP in D after intubation (p 0.05). Hypotension was effectively obtained in the two groups with a bloodless surgical field, and there was no need for additional use of a potent hypotensive agent. Figure-1. Changes of heart rate and mean arterial pressure in two groups. RD: dexmedetomidine plus remifentanil group, R:remifentanil group, *p 0.05 difference between groups, ƒ p 0.05 within D versus baseline value and p 0.05 within versus baseline value. Table-2. Intraoperative lactate concentration in arterial blood. D P value After induction 1.12± ± at 60 min 0.94± ± End of surgery 0.95± ± Data are mean ±SD, RD:dexmedetomidine plus remifentanil, R:remifentanil. Lactate concentration in arterial blood (Table-2) and intraoperative bleeding were similar in both groups (Bleeding scores, D:0.9±1.5, :0.4±1, p=0.3). The recovery time (Aldrete score 9) was faster in than in D (5.7±1.2 versus 12.7±1.7, p 0.001). There were no differences in MMST, TDT, DSST and STAI before anesthesia between the groups. In postoperative period, the MMST scores at 30 th and 120 th min were statistically better in than in Group RD. The mean STAI score was similar between the groups. However, the scores of patients in D were statistically lower in all measurements compared with preoperative values. There was no difference between the groups for anxiety scores but all the values in D decreased according to baseline (Figure-2) 4 Ege Tıp Dergisi / Ege Journal of Medicine STAI Score Percent of baseline (%) Missed Dots (n) *ƒ p=0.038 Group D 15 *ƒ p= ƒ 5 0 Baseline 30 min 60 min 120 min Time D 100 Group D ƒ ƒ ƒ ƒ ƒ Baseline 30 min 60 min 120 min Time 25 0 ƒ Baseline 30 min 60 min 120 min Time Figure-2. Changes of MMST and anxiety scores. RD: dexmedetomidine plus remifentanil, R:remifentanil.*p 0.05 difference between groups, ƒ p 0.05 within D versus baseline value. Figure-3. Psychomotor test results. Change in the TDT as number of missed dots and change in the DSST expressed according to percent of baseline. RD:dexmedetomidine plus remifentanil, R:remifentanil, *p 0.05 difference between groups, ƒ p 0.05 within D versus baseline values and p 0.05 within versus baseline. In the TDT, a significantly lower error (missed dots) score was recorded in patients receiving remifentanil alone compared with dexmedetomidin supplemented with remifentanil at the 30 th and 60 th min postoperatively but there was no difference at the 120 th min between two groups. When compared with the baseline values, TDT scores in at the 30 th and 60 th min and all measurements in D were significantly lower. The mean TDT score in reached baseline value at the 120 th min. For DSST, there were no differences between the groups and DSST scores at all time in both groups were low compared with baseline values (Figure-3). There were no postoperative complications (respiratory or cardiovascular) in the first 24 hours. At no time did oxygen saturation decrease below 97% in any group in PACU. Two patients in each group complained of nausea and one patient in suffered from vomiting. All five patients were successfully treated with ondansetron. Discussion The results of this study have shown that both groups provided controlled hypotension (target MAP) with a low rate of bleeding without the need for additional use of a potent hypotensive agent. However, recovery from anesthesia was significantly fast
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