504082 research-article2013
AOP471110.1177/1060028013504082Annals of PharmacotherapyShen et al
Research Report
Comparison of Dexmedetomidine and Propofol for Conscious Sedation in Awake Craniotomy: A Prospective, Double-Blind, Randomized, and Controlled Clinical Trial
Annals of Pharmacotherapy 47(11) 1391–1399 © The Author(s) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028013504082 aop.sagepub.com
She-liang Shen, MD1, Jia-yin Zheng, PhD2, Jun Zhang, MD1, Wen-yuan Wang, MD1, Tao Jin, PhD1, Jing Zhu, MD1, and Qi Zhang, MD1
Abstract Background: It has been reported that dexmedetomidine (DEX) can be used for conscious sedation in awake craniotomy, but few data exist to compare DEX versus propofol (PRO). Objective: To compare the efficacy and safety of DEX versus PRO for conscious sedation in awake craniotomy. Methods: Thirty patients of American Society of Anesthesiologists grade I-II scheduled for awake craniotomy, were randomized into 2 groups each containing 15 subjects. Group D received DEX and group P received PRO. Two minutes after tracheal intubation (T1), PRO (target plasma concentration) was titrated down to 1 to 4 µg/mL in group P. In group D, PRO was discontinued and DEX was administered 1.0 µg/kg followed by a maintenance dose of 0.2 to 0.7 µg/kg/h. The surgeon preset the anticipated awake point-in-time (T0) preoperatively. Ten minutes before T0 (T3), DEX was titrated down to 0.2 µg/kg/h in group D, PRO was discontinued and normal saline (placebo) 5 mL/h was infused in group P. Arousal time, quality of revival and adverse events during the awake period, degree of satisfaction from surgeons and patients were recorded. Results: Arousal time was significantly shorter in group D than in group P (P < .001). The quality of revival during the awake period in group D was similar to that of group P (P = .68). The degree of satisfaction of surgeons was significantly higher in group D than in group P (P < .001), but no difference was found between the 2 groups with respect to patient satisfaction (P = .80). There was no difference between the 2 groups in the incidence of adverse events during the awake period (P > .05). Conclusions: Either DEX or PRO can be effectively and safely used for conscious sedation in awake craniotomy. Comparing the two, DEX produced a shorter arousal time and a higher degree of surgeon satisfaction. Keywords dexmedetomidine, propofol, conscious sedation, awake craniotomy
Awake craniotomy is a reliable method of ensuring neural integrity during the excision of lesions located within or near eloquent areas.1 Currently, the “asleep–awake–asleep” technique using general anesthesia with intraoperative wake-up is considered to be the most popular pattern for awake craniotomy.2-4 Although a variety of medications have been used in awake craniotomy over the past few decades, the ideal medication for conscious sedation in this specific procedure is yet to be proven by appropriate prospective randomized, double-blind clinical trials.5 Propofol (PRO), a γ-amino-butyric acid A (GABAA) agonist, the medication commonly used for conscious sedation in awake craniotomy,6 has the advantages of rapid onset and antiemetic and antiepileptic properties.3 However, numerous studies have demonstrated the shortcomings of
PRO, including longer arousal time (39 minutes), higher total incidence of intraoperative complications/complaints (64%), and interference with the monitoring of intraoperative mapping.6-11 Dexmedetomidine (DEX), a highly selective agonist of α2-adrenergic receptors, produces dose-titrated sedation, which resembles natural sleep, decreases anxiety, pain3,12,13 1
Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, China Peking University, Beijing, China
2
Corresponding Author: Jun Zhang, MD, Department of Orthopaedics, Zhejiang Provincial People’s Hospital, Shangtang Road 158, Hangzhou, Zhejiang, 310014, China. Email: [email protected]
Downloaded from aop.sagepub.com at MCGILL UNIVERSITY LIBRARY on March 18, 2015
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Figure 1. Timeline of events and medications.
Abbreviations: RF, remifentanil; PRO, propofol; DEX, dexmedetomidine; CIS, cisatracurium besylate. Asleep (on left of the above map), initial induction of anesthesia; T0, anticipated point in time that patient is awake, set by the surgeon preoperatively; T1, 2 minutes after intubation; T2, 40 minutes before T0; T3, 10 minutes before T0; T4, actual point in time that patient is awake and can respond to commands; T5, 15 minutes after T4; T6, asleep (on right of the above map), final induction of anesthesia.
and cerebral blood flow.14 These properties make DEX a potentially advantageous sedative agent in awake craniotomy.12 Ard et al15 reported the first use of DEX as an adjunct to an asleep–awake–asleep technique in awake craniotomy. Subsequent patient series have also reported on the successful use of DEX in different age-groups, in varied airway management techniques, and combined with different anesthetics. All previous studies have indicated that DEX appears to be a useful sedative agent for conscious sedation in awake craniotomy.5,7,16-18 The advantage of remifentanil (RF) is a rapid reversal of narcosis when intraoperative consciousness is required, it appears to have emerged as the most appropriate narcotic in awake craniotomy. 5,6 Other medication in conjunction with RF for conscious sedation in awake craniotomy is common.5,6 Till date, little research has been conducted comparing DEX and PRO for conscious sedation in awake craniotomy. To compare the efficacy and safety of DEX versus PRO, we performed a prospective, double-blind, randomized, and controlled study. We hypothesized that DEX would be a more suitable sedative agent in awake craniotomy, both in efficacy and safety. Efficacy was measured by arousal time, quality of revival during the awake period and degree of satisfaction of surgeons and patients. Safety measurements included the incidence of adverse events during the awake period and vital signs immediately before, during, and after the awake period.
Methods Design and Participants The study was approved by the Ethics Committee of the Zhejiang Provincial People’s Hospital and conducted in the
operating room of Zhejiang Provincial People’s Hospital. Patients were enrolled in the study after they provided written informed consent. All patients scheduled for awake craniotomy were diagnosed with brain glioma near or within the motor cortex areas (some with secondary seizure). Exclusion criteria included known history of cardiovascular, pulmonary, or renal disease, psychiatric illness, communication difficulties, known allergies to the drugs being used, chronic exposure to opioids, women with body mass index (BMI) >35 kg/m2, men with BMI >42 kg/m2, and American Society of Anesthesiologists (ASA) physical status of III to V.19 Thirty eligible patients were randomly assigned to 2 groups (D or P) according to a randomization list. All anesthetic procedures were performed by the same anesthesiologist. All surgical procedures were performed by the same surgical team, and all data were collected by the same investigator. Patients, surgeons, and the investigator were blinded to group assignment.
Study Intervention All patients underwent “asleep–awake–asleep” technique and received detailed instruction about the technique prior to being anesthetized (Figure 1). No premedication was used. Patients’ vital signs were continuously monitored (S/5TM Entropy Module Datex-Ohmeda Division) in the perioperative period. These included heart rate (HR), electrocardiogram, pulse oxygen saturation (SpO2), noninvasive blood pressure (BP), response entropy index (RE), central venous pressure (CVP, from right internal jugular vein), and mean arterial pressure (MAP, from left radial artery). The Observer Assessment of Alertness/Sedation (OAA/S) score of patients also was observed and recorded.20
Downloaded from aop.sagepub.com at MCGILL UNIVERSITY LIBRARY on March 18, 2015
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Shen et al Preoperative baseline values of the aforementioned vital signs were recorded 5 minutes after patients were brought to the operating room. General anesthesia was induced in both groups with PRO (target-controlled infusion [TCI] Marsh modal, target plasma concentration [Cp] 4 µg/mL), cisatracurium besylate (CIS, 0.2 mg/kg, followed by a maintenance dose of 0.1 mg/kg/h), RF (TCI, Minto modal, Cp 3 ng/mL). Following adequate neuromuscular relaxation, laryngoscopy was performed and 2% tetracaine was used for topical anesthesia of glottis and subglottic region. The trachea was intubated with a cuffed endotracheal tube (lidocaine gel was put on the first one third of the tube), and the lungs were mechanically ventilated, using tidal volumes of 8 to 10 mL/kg at a rate of 10 to 12 per minute, to maintain end tidal CO2 (PETCO2) of 35 to 40 mm Hg. Two minutes after intubation (T1), RF was titrated down to 2 ng/mL (Cp) in both groups; PRO was also titrated down to 1 to 4 µg/mL (Cp) in group P but was discontinued in group D, where DEX was then administered using a loading dose of 1.0 µg/kg over 10 minutes followed by a maintenance dose of 0.2 to 0.7 µg/kg/h. The rates of infusion of DEX and PRO were adjusted accordingly to maintain RE between 40 and 60.21 Combination of 3 methods (scalp nerve block, infiltration of incision, and superficial anesthesia of dural) of local anesthesia was used with 0.25% 60mL ropivacaine hydrochloride by the surgeon. The surgeon preset the anticipated awake point in time preoperatively (T0). CIS was discontinued 40 minutes before T0 (T2) in both groups. RF was titrated down to 0.5 ng/mL (Cp) 10 minutes before T0 (T3) in both groups. At the same time (T3), DEX was titrated down to 0.2 µg/kg/h in group D. In group P, PRO was discontinued and normal saline (placebo) 5 mL/h was infused. The anesthesia ventilator rate was reduced to permit return of spontaneous ventilation at T3. After spontaneous ventilation returned and sedative level diminished as measured by RE >80, the patient’s name was shouted and repeated every 30 seconds followed by the request to open and close their fingers. When the patients moved their fingers, they were asked to move both feet. Actual awake point was defined as a patient’s ability to respond to all commands (T4). T5 was measured 15 minutes after T4. Anesthesia was again induced (T6) when the surgeon decided to stop monitoring the intraoperative mapping. PRO 0.5 mg/kg was administered intravenously for rescue sedation when cough or spontaneous movement occurred during T3–T6. Patients were transferred to postanesthetic care unit after surgery. Following the surgery, the surgeon was questioned about his degree of satisfaction with the awake period by the investigator. All patients, regardless of whether they were eligible or excluded, were interviewed 24 hours postoperatively. They were asked about their degree of satisfaction with the sedation technique, their recollection of the intraoperative
Table 1. Definition of Quality of Revival During the Awake Period. Grade I II III
IV
Definition Quiet awakening, patient can move limbs quickly and accurately according to the orders, without any spontaneous movement. Quiet awakening, patient can move limbs according to the orders, somewhat slowly and confused, without any spontaneous movement. Sudden awakening, patient can move limbs according to the orders, somewhat slowly and confused, with spontaneous movement of extremities not endangering. Dramatic awakening, patient is agitated, violent limb movements threatening stability of the device.
events, and any sensations of pain that were felt during the awake period. Adverse hemodynamic responses were recorded and classified as “hypertension” (MAP >20% above preoperative baseline value) or “hypotension” (MAP 20% above preoperative baseline values) or “bradycardia” (HR .05; Table 2). Arousal time was significantly shorter in group D than in group P (P < .001). The quality of revival in group D was similar to that in group P (P = .68 for Fisher’s exact test of 4 × 2 contingency table, P = .33 for 2 × 2 contingency table). The degree of satisfaction of surgeons was significantly higher in group D than in group P (P < .001), but no difference was found between the 2 groups with respect to the degree of satisfaction of the patients (P = .80; Table 3). The distribution of adverse events is shown in Table 4. The incidences of all adverse events during the awake period were not different between the 2 groups (P > .05; Table 5). Heart rate was significantly slower at times T2, T3, T4, T5, and T6 compared with baseline (T1) in group D (ANOVA with Dunnett’s post hoc test). HR was significantly slower at times T4, T5, and T6 in group D compared with group P (ANOVA with Student–Newman–Keuls post hoc test). RE, PETCO2, and OAA/S were significantly higher at T4–T6 than T1 in both groups (from Student–Newman–Keuls test and Dunnett’s test; Figure 3). No patients from group D required rescue sedation with PRO boluses during T3–T6, whereas group P yielded 4 such
cases. Three cases from group D and 1 case from group P required treatment for bradycardia or hypotension.
Discussion During the past decade, PRO was commonly used for conscious sedation in awake craniotomy.6 However, accumulating literature showed that patients with PRO conscious sedation usually had relative longer arousal time and higher incidence of adverse events.6-11 In our study, arousal time for group P was 16.2 minutes, incidence of quality of revival (ASA III + IV) was 26.7%, and total incidence of adverse events was 10.67%, consistent with the aforementioned reports.6-11 Recent studies have indicated that DEX appears to be a useful sedative agent in this type of neurosurgery procedure.13-16 Our aim was to compare the efficacy and safety of DEX versus PRO for conscious sedation in awake craniotomy. In our study, significant difference of arousal time was found between the patients in the DEX and PRO groups (11 vs 16.2 minutes), which is consistent with our hypothesis. The major site of noradrenergic innervation in the brain with the highest concentration of presynaptic α2-adrenergic receptors is the locus ceruleus, which is responsible for arousal, sleep, and anxiety. DEX acts at the locus ceruleus areas but does not involve the GABA receptors. Consequently, DEX provides a sedation that resembles natural sleep without cognitive impairment.12 As a result, despite the 120-minute elimination half-life of DEX,12 patients may be easily awakened by verbal stimulation without having to stop the drug infusion.24 PRO is a GABAA agonist and provides a sedation that affects recall and verbal
Downloaded from aop.sagepub.com at MCGILL UNIVERSITY LIBRARY on March 18, 2015
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Annals of Pharmacotherapy 47(11)
Table 3. Comparison of Arousal Time and Quality of Revival and the Degree of Satisfaction. Parameter
Group D (n = 15)
Arousal time in minutes, mean ± SD Quality of revival, n (%) I II III IV I + II III + IV Degree of satisfaction, median (25th/75th percentiles) Surgeons Patients
Group P (n = 15)
11.0 ± 2.3
16.2 ± 3.4
9 (60.0) 5 (33.3) 1 (6.7) 0 (0) 14 (93.3) 1 (6.7)
7 (46.7) 4 (26.7) 3 (20.0) 1 (6.7) 11 (73.3) 4 (26.7)
97 (94/98) 92 (90/95)
92 (85/93) 92 (91/94)
Test Statistics −4.88 (28)
P a
AOP471110.1177/1060028013504082Annals of PharmacotherapyShen et al
Research Report
Comparison of Dexmedetomidine and Propofol for Conscious Sedation in Awake Craniotomy: A Prospective, Double-Blind, Randomized, and Controlled Clinical Trial
Annals of Pharmacotherapy 47(11) 1391–1399 © The Author(s) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028013504082 aop.sagepub.com
She-liang Shen, MD1, Jia-yin Zheng, PhD2, Jun Zhang, MD1, Wen-yuan Wang, MD1, Tao Jin, PhD1, Jing Zhu, MD1, and Qi Zhang, MD1
Abstract Background: It has been reported that dexmedetomidine (DEX) can be used for conscious sedation in awake craniotomy, but few data exist to compare DEX versus propofol (PRO). Objective: To compare the efficacy and safety of DEX versus PRO for conscious sedation in awake craniotomy. Methods: Thirty patients of American Society of Anesthesiologists grade I-II scheduled for awake craniotomy, were randomized into 2 groups each containing 15 subjects. Group D received DEX and group P received PRO. Two minutes after tracheal intubation (T1), PRO (target plasma concentration) was titrated down to 1 to 4 µg/mL in group P. In group D, PRO was discontinued and DEX was administered 1.0 µg/kg followed by a maintenance dose of 0.2 to 0.7 µg/kg/h. The surgeon preset the anticipated awake point-in-time (T0) preoperatively. Ten minutes before T0 (T3), DEX was titrated down to 0.2 µg/kg/h in group D, PRO was discontinued and normal saline (placebo) 5 mL/h was infused in group P. Arousal time, quality of revival and adverse events during the awake period, degree of satisfaction from surgeons and patients were recorded. Results: Arousal time was significantly shorter in group D than in group P (P < .001). The quality of revival during the awake period in group D was similar to that of group P (P = .68). The degree of satisfaction of surgeons was significantly higher in group D than in group P (P < .001), but no difference was found between the 2 groups with respect to patient satisfaction (P = .80). There was no difference between the 2 groups in the incidence of adverse events during the awake period (P > .05). Conclusions: Either DEX or PRO can be effectively and safely used for conscious sedation in awake craniotomy. Comparing the two, DEX produced a shorter arousal time and a higher degree of surgeon satisfaction. Keywords dexmedetomidine, propofol, conscious sedation, awake craniotomy
Awake craniotomy is a reliable method of ensuring neural integrity during the excision of lesions located within or near eloquent areas.1 Currently, the “asleep–awake–asleep” technique using general anesthesia with intraoperative wake-up is considered to be the most popular pattern for awake craniotomy.2-4 Although a variety of medications have been used in awake craniotomy over the past few decades, the ideal medication for conscious sedation in this specific procedure is yet to be proven by appropriate prospective randomized, double-blind clinical trials.5 Propofol (PRO), a γ-amino-butyric acid A (GABAA) agonist, the medication commonly used for conscious sedation in awake craniotomy,6 has the advantages of rapid onset and antiemetic and antiepileptic properties.3 However, numerous studies have demonstrated the shortcomings of
PRO, including longer arousal time (39 minutes), higher total incidence of intraoperative complications/complaints (64%), and interference with the monitoring of intraoperative mapping.6-11 Dexmedetomidine (DEX), a highly selective agonist of α2-adrenergic receptors, produces dose-titrated sedation, which resembles natural sleep, decreases anxiety, pain3,12,13 1
Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, China Peking University, Beijing, China
2
Corresponding Author: Jun Zhang, MD, Department of Orthopaedics, Zhejiang Provincial People’s Hospital, Shangtang Road 158, Hangzhou, Zhejiang, 310014, China. Email: [email protected]
Downloaded from aop.sagepub.com at MCGILL UNIVERSITY LIBRARY on March 18, 2015
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Annals of Pharmacotherapy 47(11)
Figure 1. Timeline of events and medications.
Abbreviations: RF, remifentanil; PRO, propofol; DEX, dexmedetomidine; CIS, cisatracurium besylate. Asleep (on left of the above map), initial induction of anesthesia; T0, anticipated point in time that patient is awake, set by the surgeon preoperatively; T1, 2 minutes after intubation; T2, 40 minutes before T0; T3, 10 minutes before T0; T4, actual point in time that patient is awake and can respond to commands; T5, 15 minutes after T4; T6, asleep (on right of the above map), final induction of anesthesia.
and cerebral blood flow.14 These properties make DEX a potentially advantageous sedative agent in awake craniotomy.12 Ard et al15 reported the first use of DEX as an adjunct to an asleep–awake–asleep technique in awake craniotomy. Subsequent patient series have also reported on the successful use of DEX in different age-groups, in varied airway management techniques, and combined with different anesthetics. All previous studies have indicated that DEX appears to be a useful sedative agent for conscious sedation in awake craniotomy.5,7,16-18 The advantage of remifentanil (RF) is a rapid reversal of narcosis when intraoperative consciousness is required, it appears to have emerged as the most appropriate narcotic in awake craniotomy. 5,6 Other medication in conjunction with RF for conscious sedation in awake craniotomy is common.5,6 Till date, little research has been conducted comparing DEX and PRO for conscious sedation in awake craniotomy. To compare the efficacy and safety of DEX versus PRO, we performed a prospective, double-blind, randomized, and controlled study. We hypothesized that DEX would be a more suitable sedative agent in awake craniotomy, both in efficacy and safety. Efficacy was measured by arousal time, quality of revival during the awake period and degree of satisfaction of surgeons and patients. Safety measurements included the incidence of adverse events during the awake period and vital signs immediately before, during, and after the awake period.
Methods Design and Participants The study was approved by the Ethics Committee of the Zhejiang Provincial People’s Hospital and conducted in the
operating room of Zhejiang Provincial People’s Hospital. Patients were enrolled in the study after they provided written informed consent. All patients scheduled for awake craniotomy were diagnosed with brain glioma near or within the motor cortex areas (some with secondary seizure). Exclusion criteria included known history of cardiovascular, pulmonary, or renal disease, psychiatric illness, communication difficulties, known allergies to the drugs being used, chronic exposure to opioids, women with body mass index (BMI) >35 kg/m2, men with BMI >42 kg/m2, and American Society of Anesthesiologists (ASA) physical status of III to V.19 Thirty eligible patients were randomly assigned to 2 groups (D or P) according to a randomization list. All anesthetic procedures were performed by the same anesthesiologist. All surgical procedures were performed by the same surgical team, and all data were collected by the same investigator. Patients, surgeons, and the investigator were blinded to group assignment.
Study Intervention All patients underwent “asleep–awake–asleep” technique and received detailed instruction about the technique prior to being anesthetized (Figure 1). No premedication was used. Patients’ vital signs were continuously monitored (S/5TM Entropy Module Datex-Ohmeda Division) in the perioperative period. These included heart rate (HR), electrocardiogram, pulse oxygen saturation (SpO2), noninvasive blood pressure (BP), response entropy index (RE), central venous pressure (CVP, from right internal jugular vein), and mean arterial pressure (MAP, from left radial artery). The Observer Assessment of Alertness/Sedation (OAA/S) score of patients also was observed and recorded.20
Downloaded from aop.sagepub.com at MCGILL UNIVERSITY LIBRARY on March 18, 2015
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Shen et al Preoperative baseline values of the aforementioned vital signs were recorded 5 minutes after patients were brought to the operating room. General anesthesia was induced in both groups with PRO (target-controlled infusion [TCI] Marsh modal, target plasma concentration [Cp] 4 µg/mL), cisatracurium besylate (CIS, 0.2 mg/kg, followed by a maintenance dose of 0.1 mg/kg/h), RF (TCI, Minto modal, Cp 3 ng/mL). Following adequate neuromuscular relaxation, laryngoscopy was performed and 2% tetracaine was used for topical anesthesia of glottis and subglottic region. The trachea was intubated with a cuffed endotracheal tube (lidocaine gel was put on the first one third of the tube), and the lungs were mechanically ventilated, using tidal volumes of 8 to 10 mL/kg at a rate of 10 to 12 per minute, to maintain end tidal CO2 (PETCO2) of 35 to 40 mm Hg. Two minutes after intubation (T1), RF was titrated down to 2 ng/mL (Cp) in both groups; PRO was also titrated down to 1 to 4 µg/mL (Cp) in group P but was discontinued in group D, where DEX was then administered using a loading dose of 1.0 µg/kg over 10 minutes followed by a maintenance dose of 0.2 to 0.7 µg/kg/h. The rates of infusion of DEX and PRO were adjusted accordingly to maintain RE between 40 and 60.21 Combination of 3 methods (scalp nerve block, infiltration of incision, and superficial anesthesia of dural) of local anesthesia was used with 0.25% 60mL ropivacaine hydrochloride by the surgeon. The surgeon preset the anticipated awake point in time preoperatively (T0). CIS was discontinued 40 minutes before T0 (T2) in both groups. RF was titrated down to 0.5 ng/mL (Cp) 10 minutes before T0 (T3) in both groups. At the same time (T3), DEX was titrated down to 0.2 µg/kg/h in group D. In group P, PRO was discontinued and normal saline (placebo) 5 mL/h was infused. The anesthesia ventilator rate was reduced to permit return of spontaneous ventilation at T3. After spontaneous ventilation returned and sedative level diminished as measured by RE >80, the patient’s name was shouted and repeated every 30 seconds followed by the request to open and close their fingers. When the patients moved their fingers, they were asked to move both feet. Actual awake point was defined as a patient’s ability to respond to all commands (T4). T5 was measured 15 minutes after T4. Anesthesia was again induced (T6) when the surgeon decided to stop monitoring the intraoperative mapping. PRO 0.5 mg/kg was administered intravenously for rescue sedation when cough or spontaneous movement occurred during T3–T6. Patients were transferred to postanesthetic care unit after surgery. Following the surgery, the surgeon was questioned about his degree of satisfaction with the awake period by the investigator. All patients, regardless of whether they were eligible or excluded, were interviewed 24 hours postoperatively. They were asked about their degree of satisfaction with the sedation technique, their recollection of the intraoperative
Table 1. Definition of Quality of Revival During the Awake Period. Grade I II III
IV
Definition Quiet awakening, patient can move limbs quickly and accurately according to the orders, without any spontaneous movement. Quiet awakening, patient can move limbs according to the orders, somewhat slowly and confused, without any spontaneous movement. Sudden awakening, patient can move limbs according to the orders, somewhat slowly and confused, with spontaneous movement of extremities not endangering. Dramatic awakening, patient is agitated, violent limb movements threatening stability of the device.
events, and any sensations of pain that were felt during the awake period. Adverse hemodynamic responses were recorded and classified as “hypertension” (MAP >20% above preoperative baseline value) or “hypotension” (MAP 20% above preoperative baseline values) or “bradycardia” (HR .05; Table 2). Arousal time was significantly shorter in group D than in group P (P < .001). The quality of revival in group D was similar to that in group P (P = .68 for Fisher’s exact test of 4 × 2 contingency table, P = .33 for 2 × 2 contingency table). The degree of satisfaction of surgeons was significantly higher in group D than in group P (P < .001), but no difference was found between the 2 groups with respect to the degree of satisfaction of the patients (P = .80; Table 3). The distribution of adverse events is shown in Table 4. The incidences of all adverse events during the awake period were not different between the 2 groups (P > .05; Table 5). Heart rate was significantly slower at times T2, T3, T4, T5, and T6 compared with baseline (T1) in group D (ANOVA with Dunnett’s post hoc test). HR was significantly slower at times T4, T5, and T6 in group D compared with group P (ANOVA with Student–Newman–Keuls post hoc test). RE, PETCO2, and OAA/S were significantly higher at T4–T6 than T1 in both groups (from Student–Newman–Keuls test and Dunnett’s test; Figure 3). No patients from group D required rescue sedation with PRO boluses during T3–T6, whereas group P yielded 4 such
cases. Three cases from group D and 1 case from group P required treatment for bradycardia or hypotension.
Discussion During the past decade, PRO was commonly used for conscious sedation in awake craniotomy.6 However, accumulating literature showed that patients with PRO conscious sedation usually had relative longer arousal time and higher incidence of adverse events.6-11 In our study, arousal time for group P was 16.2 minutes, incidence of quality of revival (ASA III + IV) was 26.7%, and total incidence of adverse events was 10.67%, consistent with the aforementioned reports.6-11 Recent studies have indicated that DEX appears to be a useful sedative agent in this type of neurosurgery procedure.13-16 Our aim was to compare the efficacy and safety of DEX versus PRO for conscious sedation in awake craniotomy. In our study, significant difference of arousal time was found between the patients in the DEX and PRO groups (11 vs 16.2 minutes), which is consistent with our hypothesis. The major site of noradrenergic innervation in the brain with the highest concentration of presynaptic α2-adrenergic receptors is the locus ceruleus, which is responsible for arousal, sleep, and anxiety. DEX acts at the locus ceruleus areas but does not involve the GABA receptors. Consequently, DEX provides a sedation that resembles natural sleep without cognitive impairment.12 As a result, despite the 120-minute elimination half-life of DEX,12 patients may be easily awakened by verbal stimulation without having to stop the drug infusion.24 PRO is a GABAA agonist and provides a sedation that affects recall and verbal
Downloaded from aop.sagepub.com at MCGILL UNIVERSITY LIBRARY on March 18, 2015
1396
Annals of Pharmacotherapy 47(11)
Table 3. Comparison of Arousal Time and Quality of Revival and the Degree of Satisfaction. Parameter
Group D (n = 15)
Arousal time in minutes, mean ± SD Quality of revival, n (%) I II III IV I + II III + IV Degree of satisfaction, median (25th/75th percentiles) Surgeons Patients
Group P (n = 15)
11.0 ± 2.3
16.2 ± 3.4
9 (60.0) 5 (33.3) 1 (6.7) 0 (0) 14 (93.3) 1 (6.7)
7 (46.7) 4 (26.7) 3 (20.0) 1 (6.7) 11 (73.3) 4 (26.7)
97 (94/98) 92 (90/95)
92 (85/93) 92 (91/94)
Test Statistics −4.88 (28)
P a
