The purpose of this study was to investigate the degree of sedation and the incidence of adverse effects resulting from various methods of administering the initial dose followed by continuous infusion of dexmedetomidine (DEX) for sedation in elderly patients undergoing spinal anesthesia.
In total, 72 patients aged over 65 years who were to be administered spinal anesthesia were randomly allocated into three groups. The initial doses were injected to the groups as follows: group DD, DEX 0.5 μg/kg for 10 min; group MD, midazolam 0.02 mg/kg; and group D, no initial dose. This was followed immediately by infusing a maintenance dose of DEX 0.5 μg/kg/h to all groups.
The Bispectral index (BIS) in the D group was significantly higher than in the other two groups. There were no significant differences in the Ramsay sedation scale (RSS) among the groups. The RSS 3 level was reached in 10 min from the start of sedation in MD and DD groups and in 20 min from the start of sedation in D group. Neither bradycardia nor hypotension was observed in any of the groups.
Patients in all three groups reached the RSS 3 sedating-effect level. However, the group that received continuous infusion only without the initial dose showed higher BIS than the other two groups and reached the RSS 3 later. No adverse events were observed in any of the groups.
With advancements in medical sciences and the improved quality of life in recent years, the elderly population is consistently increasing. As a result, the number of surgeries performed on elderly patients is also rising; spinal anesthesia is the usual choice for urologic or lower-extremity surgeries. Appropriate sedation during spinal anesthesia relieves patient’s anxiety and induces loss of harmful memories.
Dexmedetomidine (DEX) is a selective α2-adrenergic agonist that triggers sedative effects by acting on the locus ceruleus, and it has been used more commonly in recent years. Some benefits of this agent include easy transition from a sedated state to an alert state that facilitates patient’s cooperation during surgery, cardiovascular stability with little respiratory depression, and a lower incidence of delirium in elderly patients [
Regional anesthesia is beneficial since the patient remains conscious and breathes spontaneously, with normal reflexes such as coughing being preserved. Although sedation is commonly induced during regional anesthesia, it is important to ensure that the patient’s consciousness is minimally diminished with no suppression of reflexes and respiration. Monitoring of the level of sedation is crucial to attain an appropriate sedation; the Bispectral index (BIS) is widely used for this purpose. The BIS enables a quantitative monitoring of the level of sedation and hypnosis on a scale from 0 to 100. The score of 70–90 indicates mild, and the score of 60–69 indicates moderate sedation [
Aging decreases tissue elasticity that lowers electrical conduction in the heart and decreases response to receptor stimulation. The diminished vascular elasticity increases the risk of hypertension, ventricular hypertrophy, and heart failure [
The purpose of this study was to investigate the degree of sedation and the incidence of adverse effects resulting from various methods of administering the initial dose followed by continuous infusion of DEX for sedation in elderly patients undergoing spinal anesthesia.
This study was approved by the institutional-review board of the authors’ affiliation (no. 2018-07-103), and a written informed consent was obtained from all patients. The study patients were aged 65 years or older and American Society of Anesthesiologists physical status classification I–II, and were scheduled to undergo a closed peritoneal surgery at perineal region under spinal anesthesia. Patients with relative or absolute contra indications for spinal anesthesia, including those with coagulopathy, skin infection, severe low back pain, or history of spinal surgery, were excluded. Seventy-two patients were randomized to three groups of 24 patients each. The author in charge of patient randomization used computer-generated random numbers with Microsoft Excel that were used to assign patients to study groups; he ensured that the patients entered the operating room as randomized, administered the intervention, and supervised the overall process.
Upon arrival at the operating room, patient’s vital signs were monitored using electrocardiography, non-invasive blood pressure, and pulse oximetry. To monitor sedation, BIS (BISTM Vista A-3000 monitor, Software version 3.20, Aspect Medical Systems, Inc., USA) and Ramsay sedation scale (RSS) scores (
The DD group, DEX (Precedex Premix, 4.72 µg/ml, Pfizer Pharmaceuticals Korea, Korea) was given at the initial dose of 0.5 μg/kg over 10 min, followed by continuous infusion of DEX at 0.5 μg/kg/h. The MD group was given midazolam at the initial dose of 0.02 mg/kg, followed by continuous infusion of DEX at 0.5 μg/kg/h. The D group was given a continuous infusion of DEX at 0.5 μg/kg/h without any initial dose. Blood pressure, heart rate, oxygen saturation, respiratory rate, BIS, RSS, and end-tidal CO2 (ETCO2) provided via a nasal cannula were measured at every stated time point after T0.
During the surgery, awareness was defined as the values of RSS being below 2 or of BIS being above 90. Hypoxia was defined as the oxygen saturation < 90%, bradycardia as the heart rate < 45 beats/min, and hypotension as the mean arterial pressure < 60 mmHg were monitored. Further, postoperative incidence of nausea, vomiting, delirium, and abnormal violent behaviors and movements were noted and assessed. Hypotension was treated with intravenous infusion of 5 mg ephedrine and bradycardia with 0.5 mg atropine. In case of hypoxia, breathing was assisted by opening the patient’s mouth and extending the neck.
Sample size was calculated using the G*Power program version 3.1.9.2 based on the Cohen’s formula. Yoon et al. [
All statistical analyses were conducted using the SPSS software (version 18.0, IBM Co., USA). Data were presented as mean ± standard deviation or the number of patients. When comparing patients’ characteristics between groups, continuous data were analyzed with one-way analysis of variance (ANOVA), and categorical data were analyzed with chi-square test or Fisher’s exact test. Variations of measures over time between groups were analyzed with repeated-measures ANOVA. Variations over time within groups were analyzed with repeated-measures ANOVA followed by post-hoc Bonferroni for continuous data. P values < 0.05 were considered statistically significant.
A total of 72 patients participated in the study, with 24 in each group (
Although the heart rate and mean arterial pressure tended to decrease during surgery, there were no significant differences among the groups after initial sedation (
BIS tended to decrease over the duration of surgery, and it significantly differed among the groups at T10 and T30. At T10, BIS was significantly higher in the D group (82.0 ± 7.7) than in the DD group (77.7 ± 5.5) and MD group (76.0 ± 5.5) (P < 0.010). At T30, BIS was significantly higher in the D group (76.6 ± 9.8) than in the DD group (71.8 ± 6.7) and MD group (72.1 ± 7.1) (P < 0.023) (
There were no significant differences in oxygen saturation and ETCO2 among the groups (
This study compared the level of sedation achieved by continuous infusion of a usual dose of DEX in elderly patients undergoing spinal anesthesia, depending on whether a) a initial dose equivalent to the half of the usual dose is used prior to continuous infusion, b) midazolam is used as the initial dose, and c) continuous infusion is begun immediately without a initial dose. All three methods led to sedation equivalent to the RSS 3. However, the BIS was higher and took longer time to achieve RSS 3 in the continuous infusion without the initial dose group compared to the other two groups. Adverse events were not observed in any of the three groups.
DEX is a selective α2-adrenergic agonist that acts on the α2A and α2B subtypes. α2A receptors are mainly distributed in the periphery, and they reduce norepinephrine secretion in the synaptic terminal and decrease sympathetic nervous activity. DEX induces sedative and analgesic effects by acting on α2B receptors present in the locus ceruleus and spinal cord, while acting on α2B receptors present in peripheral-blood vessels induces vasoconstriction. Therefore, vasoconstriction and bradycardia can commonly occur early after infusion of this drug, and hypotension can easily develop once sympathetic nervous activity is suppressed [
Riker et al. [
Yeom et al. [
DEX generates appropriate sedative effects without respiratory depression if used within the therapeutic dose [
As elderly patients were enrolled in this study, we compared three groups with a lower initial dose of 0.5 μg/kg DEX, no initial dose of DEX, and lower initial dose of 0.02 mg/kg midazolam followed by a maintenance DEX dose of 0.5 μg/kg/h. After the administration of the sedative initial dose, the three groups did not significantly differ in the mean arterial pressure and heart rate and did not show hypotension or bradycardia during surgery. Further, sedation was achieved in all three groups, though the time until sedation varied. The correlation of BIS and RSS has been reported by multiple studies. Bell et al. [
Our study involved elderly patients, and by lowering the dose of the agents, we aimed to achieve mild sedation that gives a sense of comfort during surgery without adverse events such as bradycardia, hypotension, and hypoxia. During surgery, all three groups showed a BIS level that indicated mild sedation. Although the continuous infusion only group showed a higher BIS compared to the other two groups, the score only differed by less than 6 points, and the desired sedation was achieved in all three groups without substantial clinical differences.
During the present study, we recorded intra-operative measurements every five minutes after the start of sedation; although hemodynamic instability was not observed, the results were presented in 10-min or 30-min intervals for conciseness. However, as instable vital signs can occur at any point during a surgery, the uncertainty about hemodynamic instability occurring between the indicated time points is one limitation of this study.
In conclusion, we achieved the desired sedative effect in three groups of elderly patients undergoing surgery under spinal anesthesia using a reduced initial dose of DEX or midazolam or only maintenance dose of DEX without a initial dose, with no significant differences in the heart rate and mean arterial pressure among the three groups and no occurrence of bradycardia or hypotension in any of the groups. As the desired level of sedation was achieved and continuously maintained in all three groups, these methods are believed to be hemodynamically safe and appropriate sedation methods for elderly patients.
Supplementary data containing Korean version of this article is available at
No potential conflict of interest relevant to this article was reported.
Conceptualization: Jeong Jeong, Dong Yeon Kim. Data acquisition & formal analysis: Sooyoung Cho, So Hee Jin. Supervision & writing—review & editing: Heeseung Lee, Jong In Han.
Consolidated standards of reporting trials (CONSORT) flow chart of the study. A total of 72 patients (American Society of Anesthesiologists physical status classification I–II, aged over 65 years) were randomly allocated into three groups. Group DD: initial dose of 0.5 μg/kg dexmedetomidine + continuous infusion of 0.5 μg/kg/h dexmedetomidine. Group MD: initial dose of 0.02 mg/kg midazolam + continuous infusion of 0.5 μg/kg/h dexmedetomidine. Group D: continuous infusion of 0.5 μg/kg/h dexmedetomidine without initial dose.
Trends of heart rate (A) and mean blood pressure (B). Graphs’ values are presented as mean ± SD. Group DD: initial dose of 0.5 μg/kg dexmedetomidine + continuous infusion of 0.5 μg/kg/h dexmedetomidine. Group MD: initial dose of 0.02 mg/kg midazolam + continuous infusion of 0.5 μg/kg/h dexmedetomidine. Group D: continuous infusion of 0.5 μg/kg/h dexmedetomidine without initial dose. T0: start sedation, T10, 20, 30, 60: 10, 20, 30, 60 min after sedation. There were no significant differences among the groups at any time point.
Trends of Bispectral index. Graphs’ values are presented as mean ± SD. Group DD: initial dose of 0.5 μg/kg dexmedetomidine + continuous infusion of 0.5 μg/kg/h dexmedetomidine. Group MD: initial dose of 0.02 mg/kg midazolam + continuous infusion of 0.5 μg/kg/h dexmedetomidine. Group D: continuous infusion of 0.5 μg/kg/h dexmedetomidine without initial dose. T0: start sedation, T10, 20, 30, 60: 10, 20, 30, and 60 min after sedation. Bispectral index in Group D was significantly higher than in the other two groups at T10 and T30. *P < 0.05.
Trends of oxygen saturation (SpO2) (A), end-tidal carbon dioxide (ETCO2) (B), and respiratory rate (C). Graphs’ values are presented as mean ± SD. Group DD: initial dose of 0.5 μg/kg dexmedetomidine + continuous infusion of 0.5 μg/kg/h dexmedetomidine. Group MD: initial dose of 0.02 mg/kg midazolam + continuous infusion of 0.5 μg/kg/h dexmedetomidine. Group D: continuous infusion of 0.5 μg/kg/h dexmedetomidine without initial dose. T0: start sedation, T10, 20, 30, 60: 10, 20, 30, and 60 min after sedation. There were no significant differences among the groups at any time point.
Ramsay Sedation Scale [
Score | Response |
---|---|
1 | Patient is anxious and agitated or restless or both |
2 | Patient is co-operative, oriented, and tranquil |
3 | Patient responds to commands only |
4 | Patient exhibits brisk response to light glabellar tap or loud auditory stimulus |
5 | Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus |
6 | Patient exhibits no response |
Patient’s Characteristics
Variable | Group DD (n = 24) | Group MD (n = 24) | Group D (n = 24) | P value |
---|---|---|---|---|
Age (yr) | 77.2 ± 8.1 | 74.5 ± 7.3 | 73.6 ± 7.1 | 0.231 |
Sex (M/F) | 23/1 | 23/1 | 19/5 | 0.080 |
Weight (kg) | 64.9 ± 10.8 | 68.3 ± 6.06 | 65.4 ± 10.7 | 0.392 |
Height (cm) | 167.3 ± 6.0 | 168.7 ± 5.4 | 166.9 ± 7.6 | 0.361 |
Level of spinal anesthesia | 10.2 ± 0.7 | 10.4 ± 0.8 | 9.9 ± 0.5 | 0.063 |
Operation (TURP/TURB) | 20/4 | 21/3 | 18/6 | 0.701 |
ASA physical status (I/II) | 3/21 | 8/16 | 5/19 | 0.211 |
Values are presented as mean ± SD or the number of patients. Levels of spinal anesthesia are presented as T8 = 8, L2 = 12 + 2, L4 = 12 + 4. ASA: American Society of Anesthesiologists, TURP: transurethral resection of prostate, TURB: transurethral resection of bladder. Group DD: initial dose of 0.5 μg/kg dexmedetomidine + continuous infusion of 0.5 μg/kg/h dexmedetomidine. Group MD: initial dose of 0.02 mg/kg midazolam + continuous infusion of 0.5 μg/kg/h dexmedetomidine. Group D: continuous infusion of 0.5 μg/kg/h dexmedetomidine without initial dose. There were no significant differences among the groups.
Ramsay Sedation Scale
Time point | Group DD (n = 24) | Group MD (n = 24) | Group D (n = 24) | P value |
---|---|---|---|---|
T0 | 1 (1, 1) | 1 (1, 1) | 1 (1, 1) | 0.281 |
T10 | 3 (3, 3) | 3 (3, 3) | 2.5 (2, 3) | 0.051 |
T20 | 3 (3, 3) | 3 (3, 3) | 3 (3, 3) | 0.568 |
T30 | 3 (3, 3) | 3 (3, 3) | 3 (3, 3) | 0.571 |
T60 | 3 (3, 3) | 3 (3, 3) | 3 (3, 3) | 0.358 |
Values are presented as median (1Q, 3Q). Group DD: initial dose of 0.5 μg/kg dexmedetomidine + continuous infusion of 0.5 μg/kg/h dexmedetomidine. Group MD: initial dose of 0.02 mg/kg midazolam + continuous infusion of 0.5 μg/kg/h dexmedetomidine. Group D: continuous infusion of 0.5 μg/kg/h dexmedetomidine without initial dose. T0: start sedation, T10, 20, 30, 60: 10, 20, 30, 60 min after sedation. There were no significant differences among the groups.