Edited by: Peregrine B. Osborne, University of Melbourne, Australia
Reviewed by: Kwok Ming Ho, Royal Perth Hospital, Australia; Jamie Sleigh, University of Auckland, New Zealand
*Correspondence: Yong Zhao
Chunguang Ren
This article was submitted to Neuropharmacology, a section of the journal Frontiers in Pharmacology
†These authors have contributed equally to this work.
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Chronic subdural hematoma (CSDH) usually occurs in the elderly with co-morbidities and multi-system disorders, and is one of the most frequently encountered intracranial hemorrhages in neurosurgery (Guzel et al.,
Dexmedetomidine (DEX), a highly selective agonist of the α2 adrenergic receptor, has a more favorable pharmacokinetic profile than clonidine: α2:α1 specificity ratio, 1600:1 vs. 200:1 and plasma half-life (T½), 2–2.5 h vs. 9–12 h. It also has many clinical benefits, such as sedation without significant respiratory depression, an analgesic-sparing effect, and a sympatholytic effect that can attenuate the stress response to surgery (Geloen et al.,
The institutional review board of Liaocheng People's Hospital approved (No. 2016057) this retrospective trial, which was registered at chictr.org (ChiCTR-IPR-16008494). Patients who underwent burr-hole surgery for CSDH with MAC between January 2014 and December 2015 and provided written informed consent were enrolled in this study. The inclusion criteria were: age between 45 and 65 years and ASA grade I to III. Exclusion criteria included hypertension (diastolic blood pressure > 160 mmHg); bradycardia (<50 bpm); ischemic heart disease (<6 months); second- or third-degree heart block; long-term abuse of or addiction to alcohol, tobacco, opioids, and sedative–hypnotic drugs (>6 months); allergy to DEX and/or sufentanil; neuropsychiatric diseases; operation time shorter than 30 min; emergent surgery.
Patients were divided into the following three groups: Group D1 (
No premedication was administered before surgery. Prior to starting the surgery, ASA standard monitoring five-lead electrocardiography, non-invasive arterial blood pressure, peripheral pulse-oximetry (SpO2), respiratory rate (RR), and temperature were continuously monitored using an automated system (Philips IntelliVue MP50). Oxygen supplementation at 3 L·min−1 was achieved through an oxygen mask; then, an 18-gauge intravenous catheter was placed in a peripheral vein under local infiltration anesthesia. A forced-air warming device (EQUATOR Convective Warmer, EQ-5000) was used during the surgery to maintain normothermia.
Patients in the D1 and D2 groups received an initial loading dose of 0.5 μg·kg−1 and 1 μg·kg−1 DEX, respectively, over 10 min followed by a maintenance infusion of 0.2–0.7 μg·kg−1·h−1 to achieve adequate sedation. Patients in group S received an initial loading dose of 0.3 μg·kg−1 sufentanil over 10 min followed by a maintenance infusion of 0.1–0.3 μg·kg−1·h−1 to achieve adequate sedation. The target RSS of the three groups was 3 (patient exhibits response to commands). A rescue bolus of midazolam 0.02 mg·kg−1 was repeated every 5 min to a maximum dose of 2.5 mg if RSS > 3 or movement was noted during the procedure, while fentanyl 1 μg·kg−1 was repeated every 5 min to a maximum dose of 0.2 mg if the pain score (visual analog scale, VAS) >4. If the patient did not reach the ideal status after the maximum dose of midazolam and fentanyl was reached, propofol or GA was administered. Once patients showed the ideal state of sedation, the scalp was infiltrated with 5 mL of a local anesthetic solution containing 2.5 mL of 0.5% hydrochloride ropivacaine and 2.5 mL of 2% lidocaine with adrenaline at each burr hole site. DEX and sufentanil infusion were stopped when the drainage tube was fixed. All patients received 5 mg of tropisetron and were transferred to the post-anesthesia care unit (PACU) after surgery.
On arrival at the PACU, vital signs (HR, non-invasive blood pressure, RR, SpO2, temperature), RSS, and VAS were monitored every 5 min for the first 20 min, then every 10 min for the rest of the time until the patients were discharged to the wards (Aldrete Score ≥ 9) (Mason et al.,
During the surgery, bradycardia and tachycardia were defined as HR <45 bpm decrease or >120 bpm increase from baseline and treated with intravenous atropine, 0.2 mg, or esmolol, 0.4 mg·kg−1, respectively. Hypertension and hypotension were defined as a >20% increase or decrease from baseline and treated using urapidil (10–15 mg) or phenylephrine (20–80 μg), respectively. All patients were closely continuously monitored with the aid of five-lead electrocardiography and non-invasive arterial blood pressure, SpO2, and RR readings using an automated system (Philips IntelliVue MP50) for 48 h after surgery.
The intraoperative hemodynamic data (HR, non-invasive blood pressure, RR, SpO2, temperature) were obtained from a Philips IntelliVue monitor at the following time points: arrival at the operating room (T1); after bolus administration of drug (T2); before administration of local anesthetic (T3); before skin incision (T4); at 5 min (T5) and 10 min (T6) after skin incision; and at arrival (T7), 5 min (T8), and 10 min (T9) at the PACU. Anesthesia onset time (from the initiation of anesthesia induction to the onset of the surgical procedure), recovery time (from stopping the DEX or sufentanil infusion to achieve RSS = 2), total number of intraoperative patient movements, amount of rescue midazolam or fentanyl, time to first dose of rescue midazolam or fentanyl, percentage of patients converted to alternative sedative or anesthetic therapy, adverse events, and patient and surgeon satisfaction scores were recorded.
The Kolmogorov–Smirnov test was used to assess the distribution of variables. Homogeneity of variance was determined using Levene's tests. Quantitative data were expressed as mean and standard deviation or median and inter-quartile range (IQR). Inter-group comparisons were performed using repeated-measures analysis of variance (ANOVA). The Bonferroni's correction was applied for
Figure
Age (y) | 57.53 ± 9.33 | 59.02 ± 8.92 | 55.69 ± 7.92 | 0.070 |
Body weight (kg) | 72.39 ± 8.43 | 69.83 ± 9.34 | 71.98 ± 7.20 | 0.144 |
Sex (male/female) | 42/25 | 43/32 | 50/23 | 0.380 |
BMI (kg·m−2) | 23.39 ± 3.12 | 24.02 ± 2.92 | 23.87 ± 2.78 | 0.419 |
ASA (I/II/III) | 18/40/9 | 15/48/12 | 15/51/7 | 0.623 |
Preoperative GCS | 14.78 ± 1.09 | 14.88 ± 0.92 | 14.82 ± 1.03 | 0.838 |
Hematoma volume (mL) | 52.19 ± 12.29 | 56.29 ± 14.82 | 52.95 ± 15.37 | 0.187 |
Duration of anesthesia (min) | 72.23 ± 14.24 | 78.29 ± 17.74 | 75.89 ± 18.24 | 0.104 |
Duration of surgery (min) | 47.24 ± 9.83 | 51.29 ± 11.20 | 48.93 ± 11.06 | 0.080 |
Comorbidity, |
0.991 | |||
Hypertension | 45 (67.16%) | 48 (64.00%) | 42 (57.53%) | |
Arrhythmia | 8 (11.94%) | 12 (16.00%) | 11 (15.07%) | |
Diabetes mellitus | 9 (13.43%) | 11 (14.67%) | 8 (10.96%) | |
COPD/asthma | 3 (4.48%) | 4 (5.33%) | 2 (2.74%) | |
Anemia | 13 (19.40%) | 16 (21.33%) | 10 (13.70%) |
Baseline vital signs were not statistically different among the three groups (
Upon intergroup comparison, we found that anesthesia onset time was significantly shorter in group D2 (17.36 ± 4.23 vs. 13.42 ± 2.12 vs. 15.98 ± 4.58 min, respectively, for D1, D2, S;
Hematoma volume (mL) | 52.19 ± 12.29 | 56.29 ± 14.82 | 50.95 ± 15.37 | 0.061 |
Duration of anesthesia (min) | 72.23 ± 14.24 | 78.29 ± 17.74 | 75.89 ± 18.24 | 0.104 |
Duration of surgery (min) | 47.24 ± 9.83 | 51.29 ± 11.20 | 48.93 ± 11.06 | 0.080 |
Anesthesia onset time (min) | 17.36 ± 4.23 | 13.42 ± 2.12 |
15.98 ± 4.58 |
0.000 |
Time to first dose of rescue midazolam (min) | 17.32 ± 4.47 | 23.56 ± 5.36 |
16.55 ± 4.91 | 0.000 |
Time to first dose of rescue fentanyl (min) | 18.47 ± 3.74 | 18.56 ± 2.92 | 18.24 ± 3.65 | 0.845 |
Total cumulative dose of dexmedetomidine (μg) | 65.39 ± 18.53 | 92.15 ± 23.27 |
0 |
0.000 |
Total patient movements, |
32 (47.76%) | 15 (20.00%) |
35 (47.95%) | 0.000 |
Converted to alternative sedative, |
4 (5.97%) | 0 (0.00%) |
5 (6.85%) | 0.006 |
Total number of patient movements during the burr-hole surgery was higher in groups D1 and S (47.76 vs. 20.00 vs. 47.95%, respectively, for D1, D2, S;
The time to recovery for discharge from the PACU (i.e., time to Aldrete score ≥9) was significantly shorter in group D2 than in groups S and D1 (16.24 ± 4.15 vs. 12.48 ± 3.29 vs. 15.91 ± 3.66 min, respectively, for D1, D2, S;
Recovery time (min) | 16.24 ± 4.15 | 12.48 ± 3.29 |
15.91 ± 3.66 | 0.000 |
Patient satisfaction score | 6.00 (5.25–7.00) | 6.75 (5.75–7.00) |
6.25 (5.25–6.75) | 0.035 |
Surgeon satisfaction score | 1.75 (1.00–2.75) | 3.25 (2.75–4.00) |
2.00 (1.25–3.00) | 0.012 |
More patients in groups D1 and S than group D2 required higher doses of urapidil (41.79 vs. 20.00 vs. 34.25%, respectively, for D1, D2, S;
Urapidil | 28 (41.79%) | 15 (20.00%) |
25 (34.25%) | 0.017 |
Esmolol | 22 (32.84%) | 12 (16.00%) |
23 (31.51%) | 0.038 |
Phenylephrine | 8 (11.94%) | 9 (12.00%) | 10 (13.70%) | 0.950 |
Atropine | 6 (8.96%) | 7 (9.33%) | 5 (6.85%) | 0.824 |
The main adverse events are shown in Table
Tachycardia | 27 (40.30%) | 15 (20.00%) |
25 (34.25%) | 0.008 |
Hypertension | 30 (44.78%) | 17 (22.67%) |
27 (36.99%) | 0.013 |
Bradycardia | 8 (11.94%) | 10 (13.33%) | 7 (9.59%) | 0.807 |
Hypotension | 7 (10.45%) | 11 (14.67%) | 9 (12.33%) | 0.745 |
Nausea | 6 (8.96%) | 5 (6.67%) | 7 (9.59%) | 0.797 |
Vomiting | 2 (2.99%) | 1 (1.33%) | 2 (2.74%) | 0.744 |
Respiratory depression | 0 (0%) | 0 (0%) |
6 (8.22%) |
0.004 |
Compared with sufentanil, DEX infusion at 1.0 μg·kg−1 could decrease the number of intraoperative patient movements, which may be the primary reason for better patient and surgeon satisfaction scores found in the D2 group. In this study, we also found that the time to recovery from the PACU (i.e., time to Aldrete score ≥9) was significantly shorter in group D2 than in groups S and D1, likely because fewer patients in this group required rescue drugs. Four patients from group D1 and five from group S needed to convert to alternative sedation with propofol, although no patient required GA to complete the burr-hole surgery. Hypotension and bradycardia were the most common adverse events reported previously during the DEX infusion period; however, we did not find any significant differences among the three groups, and the few side effects seen were only mild or moderate in severity and responded well to intervention. Patients in group D2 also showed lower levels of tachycardia and hypertension. An important finding of our study was that a higher incidence of clinically significant respiratory depression was observed in the sufentanil group than in both DEX groups.
Monitored anesthesia care has been widely used in many clinical fields such as gastrointestinal endoscopy, septoplasty, thyroplasty, interventional or radiological procedures, cataract surgery, and awake bronchoscopy intubation (Bekker and Sturaitis,
Intraoperative patient movement is one of the most common causes of complications during surgery, which is often because of inadequate sedation levels and analgesia. In this study, the incidence of total patient movements was least in the D2 groups and comparable in groups D1 and S. Our results are consistent with a previous study by Bekker et al. had reported. (Bekker et al.,
In our study, the patient satisfaction score was higher in group D2 than in groups D1 and S. Patient satisfaction is a direct measure of the anesthetic care quality during surgery. A similar result was reported by Alhashemi, who attributed this finding to the analgesic property of DEX (Alhashemi,
Previous studies have reported that higher concentrations of DEX can result in fatal adverse effects, especially by affecting the cardiovascular system (Ebert et al.,
We acknowledge that our study has some limitations. First, this study was designed as a retrospective trial, while a multi-center prospective design would have been more appropriate to verify the feasibility of DEX alone used during burr-hole surgery for CSDH. Second, although DEX was administered at a rate of 1.0 μg·kg−1 for 10 min, and then continued at a rate of 0.2–0.7 μg·kg−1·h−1 throughout the duration of the operation, we were unable to measure the serum concentration of DEX owing to technical limitations and increasing hospital costs. Third, six patients experienced respiratory depression in group S, which may be due to the high dose of sufentanil used in this study. Lastly, patients treated with beta-blockers and clonidine before surgery who developed bradycardia (<50 bpm) during the loading dose of DEX may not be suitable for this mode of anesthetic administration. In future, more studies should be carried out to verify the feasibility of different doses of sufentanil alone, or in combination with other drugs, in burr-hole surgery.
In summary, our study showed that compared with sufentanil, DEX infusion at 1 μg·kg−1 for 10 min (and subsequently adjusted to 0.2–0.7 μg·kg−1·h−1) alone could decrease the number of intraoperative patient movements and amount of rescue scheme, shorten postoperative recovery time, and provide better patient and surgeon satisfaction. At the same time, no severe adverse effects were recorded in either DEX group. Thus, DEX at the studied doses is a safe and effective primary sedation alternative to traditional opioids in patients undergoing MAC for burr-hole surgery.
YZ, CR, and WW conceived and designed the trial; LF and WW collected the data; WW and FB analyzed the data; and ZZ, YZ, CR, and WW wrote this paper. YZ and CR contributed equally to this trial and considered as corresponding authors.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.