Ir J Med Sci DOI 10.1007/s11845-014-1178-0

ORIGINAL ARTICLE

Effects on somatosensory and motor evoked potentials of senile patients using different doses of dexmedetomidine during spine surgery Z. Chen • S. Lin • W. Shao

Received: 4 April 2014 / Accepted: 25 July 2014 Ó Royal Academy of Medicine in Ireland 2014

Abstract Objective The aim of this study was to evaluate the effects of different doses of dexmedetomidine (Dex) compounded propofol and fentanyl on intraoperative somatosensory evoked potential (SEP) and motor evoked potential (MEP) monitoring on senile patients. Methods Forty-five patients undergoing elective spinal surgery were randomly divided into three groups: group C, group D1 (Dex, 0.3 lg kg-1 h-1), and group D2 (Dex, 0.8 lg kg-1 h-1). Anesthesia administration: midazolam, propofol, fentanyl, and cisatracurium. Anesthesia maintenance: propofol and fentanyl. No muscle relaxant was used throughout the operation. When muscle relaxation was T4/ T1 [ 75 %, SEPs and MEPs were monitored for the baseline. In group D1, Dex (0.3 lg/kg, loading dose) was administered, followed by a 0.3 lg kg-1 h-1 infusion of said drug until the end of surgery. In group D2, Dex (0.8 lg/kg, loading dose) was injected, followed by a 0.8 lg kg-1 h-1 infusion of said drug. Results Compared with group C, no significant difference was observed in the amplitude and latency of SEP (P15–N20) waves in groups D1 and D2 (P [ 0.05). In groups C and D1, the MEP waveform did not disappear at every stage. In group D2, three patients lost the MEP waveform after the Dex loading dose, while four patients lost it during the Dex infusion stage. A significant difference was observed between groups C and D1. The median time to recover the MEP waveform was 47 min. Conclusions Dex did not affect SEPs of senile patients, but inhibited MEPs when larger doses were administered. Z. Chen  S. Lin (&)  W. Shao Department of Anesthesiology, Yantaishan Hospital, No. 91 Jiefang Road, Yantai 264001, China e-mail: [email protected]

Keywords Anesthesia  General  Senile  Intravenous  Evoked potentials  Medetomidine  Propofol

Introduction The spinal cord or spinal nerve can be injured during spinal surgery. Intraoperative somatosensory evoked potential (SEP) and motor evoked potential (MEP) monitoring can provide warning of spinal cord or spinal nerve injury, thus encouraging their use during such surgery [1, 2]. Total intravenous anesthesia is common in this kind of surgery because of the influence of inhalation anesthetics on MEPs [3, 4]. Dexmedetomidine (Dex), which functions as an adjuvant, can facilitate smooth recovery and provide adequate analgesia during total intravenous anesthesia and the postoperative period [5]. A recent study on adults undergoing spinal surgery recently reported that the use of Dex caused no significant changes on SEPs and MEPs in adolescents [6]. However, the effects of Dex on SEPs and MEPs in senile patients undergoing spinal surgery were not studied. Therefore, we designed this prospective study to observe the changes in intraoperative SEPs and MEPs in senile patients undergoing spinal surgery, using different doses of Dex.

Materials and methods Patients and groups Forty-five patients between the ages of 65 and 80 years and of both genders (ASA II–III, muscle strength III–V) were included in the study. Patients were randomized into three groups (n = 15 each): group C, group D1

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(0.3 lg kg-1 h-1), and group D2 (0.8 lg kg-1 h-1). In all cases, height was not restricted. However, patients with the following conditions were excluded from the study: injury of nerve conduction pathways, intracranial hypertension syndrome, diabetic peripheral neuropathy, and myasthenia gravis. This study was conducted in accordance with the declaration of Helsinki. This study was conducted with approval from the Ethics Committee of Yantaishan Hospital. Written informed consent was obtained from all participants.

SiLugao High-tech Development Co., Ltd., China). In group D2, Dex (0.8 lg/kg) was injected for 10 min as a loading dose, and then pumped at 0.8 lg kg-1 h-1. The other drugs were similar to those administered in group C. Muscle relaxant was not administered to any of the three groups in the succeeding time. All patients were provided with a controlled ventilation frequency of 12 bpm. The infusion of oxygen was 1–5 mL/min, and the ratio of inspiration to expiration was 1:2. During the operation, Pet CO2 was maintained between 35 and 45 mmHg (1 mmHg = 0.133 kPa).

Anesthesia methods SEP monitoring [7–9] Phenobarbital sodium (0.1 g) and atropine (0.5 mg) were injected intramuscularly 30 min before anesthesia. The electrocardiogram and oxygen saturation were monitored routinely. Invasive arterial pressure was monitored in the radial artery. Then, 0.9 % NaCl and 6 % hydroxyethyl starch (batch number: 10122821, Qingdao Shouhe Development Co., Ltd., Qingdao, Shandong Province, China) were injected at a 1:1 ratio until the end of the operation. The speed of infusion was adjusted according to hemodynamics and was then maintained until the end of the operation. The methods of anesthesia induction were the same among the three groups. Anesthesia induction: Propofol (batch number: 11042-02, Qingyuan Jiabo Development Co., Ltd., Qingyuan, Guangdong Province, China) was administered via the target-controlled infusion (TCI) mash model (Beijing SiLugao High-tech Development Co., Ltd., China), with a target plasma concentration of 1.5–2 lg/mL. Fentanyl (batch number: 100912, Renfu Medicine Development Co., Ltd., Yichang, Hubei Province, China) was administered at 1.5–2 lg/kg. After the patient lost consciousness, cisatracurium was injected, and a 7# endotracheal tube was inserted to maintain ventilation. Anesthesia maintenance In all cases, the bispectral index (BIS) was used to monitor the depth of sedation, with the BIS maintained between 45 and 55 by varying the targeted blood level of propofol (2–3 lg/mL). Simultaneously, fentanyl was administered internally to maintain the depth of analgesia. In group C, anesthesia was maintained with TCI of propofol and intermittent injection of fentanyl. Dex was administered when muscle relaxation was monitored at T4/ T1 [ 75 %. In group D1, Dex (batch number: 10122134, Jiangsu Hengrui Development Co., Ltd., Lianyungang, Jiangsu Province, China) (0.3 lg/kg) was injected for 10 min (lot number: 10082534, JiangSu Hengrui Medical Co., Ltd., China) as a loading dose, and then was pumped at 0.3 lg kg-1 h-1 through a TCI-III pump (Beijing

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All monitoring was performed using an Endeavor CR 16 neurophysiological detector. Initial SEP signals (pre-baseline) were obtained after inserting the laryngeal mask airway (LMA). Baseline signals were obtained before surgery commenced. Continuous upper and lower extremity stimulation was performed simultaneously throughout the surgical procedure every 10 min. Stimulation was accomplished with square-wave electrical pulses of 0.3 ms duration at an intensity of 10–15 mA and a frequency of 5.1 Hz. SEPs were monitored after bilateral median and ulnar nerve stimulation at the wrist, and posterior tibial nerve stimulation at the ankle, using subdermal needle electrodes. Evoked potentials were recorded in a referential and differential manner from multiple scalp electrodes (international 10–20 system: Cz, C3, C4, and FpZ) as well as a linked ear electrode. The filter bandwidth was 10–500 Hz, and scanning duration was 100 ms superimposing 100 times. SEP amplitudes were defined as peak-topeak amplitudes. MEP monitoring [7–9] For MEPs, multi-pulse transcranial electrical stimulation was generated by an Endeavor CR 16 neurophysiological detector. Pre-baseline MEP signals were obtained after induction of LMA, and baseline MEP signals were obtained after muscle relaxation was monitored at T4/ T1 [ 75 % (using the Endeavor CR 16). Stimulation was applied using short trains of four square-waves, monophasic, anodal, constant-current electrical pulses of 500–1,000 ms duration. This process was performed with an interstimulus interval of 2 ms, at sites 2 cm anterior to the C1/C2 position of the international 10–20 system. Stimulus intensity ranged from 200 to 400 V. MEPs were recorded simultaneously from abductor hallucis, anterior tibialis, and abductor pollicis brevis muscles bilaterally using subdermal needles in the muscles with a distant reference electrode.

Ir J Med Sci

SEP and MEP monitoring criteria

Table 1 Comparison (mean ± SD)

SEP waveforms were analyzed for latency and peak-topeak amplitude. Critical SEP changes were defined as decreases in amplitude of more than 50 % of baseline values or increases in latency of more than 10 % of baseline values. A positive result was defined as the amplitude loss of MEPs at any of the six muscles. Systemic parameters or other potential factors were similar for the two groups. These parameters included blood pressure and body temperature. Once a positive SEP or MEP event occurred, surgery was discontinued. For patients with a positive result, surgical procedures were reviewed to determine whether an intra-surgical intervention occurred. Simultaneously, Dex administration was stopped. If the waveform was not continually recovered, a wake-up test was performed. In this case, the patient involved was excluded from the study.

Group

Data recording Heart rate (HR), MAP, and the amplitudes and latency of SEPs (P15–N20) were recorded at the following time points: Before Dex administration (baseline), after Dex loading dose administration (T1), and 1 h after administration of continuous Dex infusion (T2). The positive event number of MEPs was statistically analyzed for the period before Dex administration, at the loading dose Dex stage, and at the continuous infusion stage. Statistical analysis

of

general

indicators

of

the

patients

N

Gender (male/female)

Age (years)

Height (cm)

Weight (kg)

Operation time

C

14

10/4

71 ± 4

161 ± 11

64 ± 7

88 ± 24

D1

14

8/6

71 ± 6

163 ± 11

65 ± 5

82 ± 19

D2

15

9/6

67 ± 5

166 ± 10

65 ± 8

87 ± 22

P [ 0.05, no significant difference in all the three groups

Among the three groups, no significant differences in patient sex, age, cases of senility (age [65 years), height, or operation time were observed (P [ 0.05, Table 1). Comparison of propofol dose, fentanyl dose, infusion volume and blood loss Compared with group C, the doses of propofol and fentanyl in groups D1 and D2 were decreased (P \ 0.05, Table 2). Comparison of HR and MAP Compared with group C, HR decreased in groups D1 and D2. Compared with group C, no significant difference of MAP in group D1 (P [ 0.05) was observed, but a significant difference of MAP in group D2 was noted (P \ 0.05, Table 3). Comparison of the amplitude and latency of SEP (P15–N20) waves

All data were analyzed using SPSS 11.0 statistics software. All measurement data were expressed as the means ± standard deviations (x ± SD). Groupwise t tests were used to compare the differences among groups. A repeated measures analysis of variance (ANOVA) was used to compare intragroup differences. Chi-square tests (v2 test) were used to compare the differences of enumeration data. The critical statistical significance threshold was P \ 0.05.

Compared with group C, no significant difference was observed in the amplitude and latency of SEP (P15–N20) waves in groups D1 and D2 (P [ 0.05, Table 4; Fig. 1a). In groups C and D1, the waveform of MEPs did not disappear at every stage. Three patients exhibited a loss of MEP waveform after the Dex loading dose, and four patients lost the waveform during the Dex infusion stage, in group D2 (Table 5). A significant difference was observed in groups C and D1. The median time to recover the MEP waveform was 47 min (see muscle relaxation monitoring in Fig. 1b).

Results

Discussion

General data

Senile patients exhibit impairment of physiological functions and often experience more than one illness. Therefore, senile patients are sensitive to many drugs, especially central-acting sedatives. In addition, their tolerance and dose requirements decrease, weakening the autonomic self-control capability of their nervous systems. With Dex administration, an increase in sedation

Among the 45 patients, two were excluded from the study. One patient was excluded because the patient’s waveform was less than SEPs and MEPs, because of the operation. Another case was excluded because the patient’s HR decreased acutely.

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Ir J Med Sci Table 2 Comparison of propofol dose, fentanyl dose, infusion volume and blood loss (mean ± SD) Group

N

Propofol dose (mg)

Fentanyl dose (mg)

Infusion volume (ml)

Blood loss (ml)

1,080 ± 40

C

14

0.68 ± 0.04

1,100 ± 130

330 ± 45

D1

14

850 ± 60a

0.55 ± 0.04a

1,150 ± 200a

350 ± 50

D2

15

820 ± 72a

0.40 ± 0.08b

1,200 ± 250b

270 ± 80

a

P \ 0.05, compared with group C

b

P \ 0.05, compared with group D1

Table 3 Comparison of HR and MAP

HR

MAP

Group

N

Baseline

C

14

76 ± 7

T1

N

T2

67 ± 7a

Baseline

63 ± 6a

a,b

52 ± 4a,b 53 ± 7a,b

14

0

0

0

D1

14

0

0

0

D2

15

0

3a,b

4a,b

75 ± 8 73 ± 10

C

14

143 ± 15

107 ± 14

114 ± 12

D1

14

147 ± 13

109 ± 18

113 ± 17

a

P \ 0.05, compared with group C

117 ± 13

b

P \ 0.05, compared with group D1

152 ± 18

c

116 ± 13

Continuos infusion stage

C

14 15

15

56 ± 6 58 ± 7a,b

Loading dose Dex stage

D1 D2

D2 a

Table 5 Comparison of positive cases of MEPs

P \ 0.05, compared with baseline

b

P \ 0.05, compared with group C

c

P \ 0.05, compared with group D1

Most anesthesia influenced SEPs and MEPs significantly [14, 15], so the process of excluding anesthesia factors from evoked potential monitoring is important to obtain the correct monitoring result. SEPs refer to the potentials conducted from the peripheral nerve to the contralateral somatosensory cortex when the peripheral nerve is stimulated. They reflect the functional integrity of the peripheral nerve, posterior spinal cord, brainstem, bulbar fillet, capsula interna, and contralateral somatosensory cortex. SEPs mainly showed effects at the cortical level. However, Dex affected the locus ceruleus beside the fourth ventricle, unlike traditional sedating drugs [16]. In our study, different Dex concentrations had no effect on SEPs, a finding consistent with our assumption. In some studies [17–19], Dex was also found to have no effect on SEP monitoring. We speculate that this is related to the sites of action. Dex also affected the locus ceruleus, which has no direct inhibitory effect on the cortex. Therefore, no significant effect was observed on the evoked potential that occurred in the cortex. MEPs are electric reactions from the muscle, which can be used effectively when monitoring stimulated areas of the brain. MEP is affected by patient muscle tonus. Three

depth often causes bradycardia. In our study, various degrees of bradycardia occurred in all patients during surgery when Dex was administered. Although no statistical difference was observed among groups, a change in concentration within the clinical medicine concentration range slightly altered HR. However, delicate and accurate anesthesia depth monitoring is still required. In recent years, the objective indicators of anesthesia depth monitoring were mostly quantitative electroencephalographic indicators, such as the bispectral index (BIS) and brainstem auditory evoked potential [10, 11]. BIS has been considered the most sensitive and accurate objective indicator in assessing consciousness, sedation, and depth of anesthesia [12]. BIS can identify minute changes earlier than MAP, and correlates well with degree of sedation, such that lower values represent deeper sedation [13]. In surgery, we found that doses of propofol and fentanyl for the maintenance of the same sedation depth were lower, which indicated that Dex had a strong effect on analgesia and sedation. Table 4 Comparison of the amplitude, latency of SEPs (P15–N20) waves

Group The amplitude (SEPs lv)

Latency (SEPs ms) P [ 0.05, no significant difference in all the three groups

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N

T0

T1

T2

C

14

0.89 ± 0.08

0.78 ± 0.12

0.79 ± 0.07

D1

14

0.94 ± 0.08

0.81 ± 0.09

0.84 ± 0.08

D2

15

0.89 ± 0.10

0.76 ± 0.08

0.78 ± 0.08

C

14

36 ± 14

35 ± 7

36 ± 10

D1

14

33 ± 8

36 ± 7

36 ± 10

D2

15

32 ± 12

33 ± 11

37 ± 13

Ir J Med Sci

Fig. 1 a SEPs monitoring; b MEPs monitoring

patients lost MEP amplitude when we continuously pumped higher doses of Dex during surgery, and this finding was significantly different from the previous study on young people [4, 6]. However, it was consistent with the result of some other studies [17, 20]. The possible cause for the loss of MEP amplitude may be the increased depth of anesthesia produced with a high bolus of dexmedetomidine. The results herein also indicated that low concentrations of Dex may be used as an anesthetic adjunct to propofol– fentanyl TIVA in procedures that require MEP and SEP monitoring among senile patients. Increasing the dose of Dex may depress the amplitude of MEPs, but this method has no effect on SEPs. Therefore, clinicians should administer small doses of Dex when MEP and SEP monitoring needs to be applied in senile patients being administered anesthesia. Conflict of interest All authors have no conflict of interest regarding this paper.

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Effects on somatosensory and motor evoked potentials of senile patients using different doses of dexmedetomidine during spine surgery.

The aim of this study was to evaluate the effects of different doses of dexmedetomidine (Dex) compounded propofol and fentanyl on intraoperative somat...
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