|Year : 2020 | Volume
| Issue : 1 | Page : 31-40
Quasi-experiment as an initial experience for conscious sedation in awake craniotomy: dexmedetomidine versus midazolam
Salwa H Waly1, Yasser M Nasr1, Ahmed A Morsy2
1 Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Zagazig University, Zagazig, Egypt
2 Department of Neurosurgery, Faculty of Medicine, Zagazig University, Zagazig, Egypt
|Date of Submission||08-Dec-2018|
|Date of Acceptance||17-Apr-2019|
|Date of Web Publication||16-Apr-2020|
MD Salwa H Waly
17 El Khashab Street behind El Mabarra Hospital, Zagazig, Al Sharkia 44511
Source of Support: None, Conflict of Interest: None
Background Awake craniotomy with intraoperative brain mapping in the surgical management of brain lesions at eloquent areas has been reported to be associated with better neurological outcome and more extensive resection. Conscious sedation avoids the risks of general anesthesia, reduces the rate of ICU admissions, and shortens the length of hospital stay.
Aim of the study The aim of the is to compare the efficacy and safety of dexmedetomidine with midazolam during procedural sedation of awake craniotomy patients.
Patients and methods A quasi-experiment conducted upon 24 awake craniotomy patients. Patients were of American Society of Anesthesiologists I/II, of both sexes, 21–65 years. Scalp block was done. The patients were divided into two groups: group D is the dexmedetomidine group (n=12) and group M is the midazolam group (n=12). Group D: 1 µg/kg dexmedetomidine was administered intravenously over 20 min, followed by continuous infusion of 0.1–0.7 µg/kg/h. Fifteen minutes before starting cortical mapping, the dose of dexmedetomidine was reduced to 0.1 µg/kg/h. Group M: midazolam was administered as an intravenous loading dose of 0.1 mg/kg given slowly over 10 min followed by infusion of 0.03–0.2 mg/kg/h. Fifteen minutes before starting cortical mapping, the dose of midazolam was reduced to 0.03 mg/kg/h.
Results Success rate was significantly higher in group M compared with group D (100 vs. 91.7%). Duration of postoperative recovery from sedation was statistically significantly longer in group M compared with group D (24±1 vs. 18±8). Three (25%) cases in group D experienced intraoperative seizures and one (8.3%) case could not be controlled and awake technique was aborted. Patients had memories of the procedure (66.7% in group D to 16.7% in group M) with statistically significant difference.
Conclusion Both dexmedetomidine and midazolam were safe and efficient during awake craniotomy. Midazolam had a higher success rate, lower incidence of intraoperative seizures, and higher incidence of amnesia. Dexmedetomidine had more rapid recovery.
Keywords: awake craniotomy, dexmedetomidine, midazolam
|How to cite this article:|
Waly SH, Nasr YM, Morsy AA. Quasi-experiment as an initial experience for conscious sedation in awake craniotomy: dexmedetomidine versus midazolam. Res Opin Anesth Intensive Care 2020;7:31-40
|How to cite this URL:|
Waly SH, Nasr YM, Morsy AA. Quasi-experiment as an initial experience for conscious sedation in awake craniotomy: dexmedetomidine versus midazolam. Res Opin Anesth Intensive Care [serial online] 2020 [cited 2020 May 31];7:31-40. Available from: http://www.roaic.eg.net/text.asp?2020/7/1/31/282584
| Introduction|| |
The new technologies in neurodiagnostic techniques and neurosurgery created a chance for the management of some cases that were considered before as difficult to manage or unmanageable. However, these advancements created also a challenge for the neuroanesthesiologists to cope with .
The common indication for awake craniotomy has been surgical management of epilepsy especially temporal lobectomy where the excision is near an eloquent area (motor and speech areas). Tumors or arteriovenous malformations invading the speech, motor, sensory, or visual cortex might need intraoperative functional testing or cortical mapping which necessitates an awake patient. Moreover, some supratentorial craniotomies are also performed under procedural conscious sedation in many neurosurgical institutes .
Awake craniotomy as an anesthetic technique is based upon local anesthesia (LA) with sedation that requires the patients to be conscious and cooperative during a certain neurosurgical procedure ,. Many anesthetic protocols for awake craniotomy have been described, some of which have been based on monitored anesthesia care, while others have been based upon general anesthesia with periods of awakening. However, none of these protocols can be called the best anesthetic technique .
Sedation, hypnosis, and analgesia using short-acting drugs (allowing recovery within 5–20 min) together with scalp block are the basis for a good plan for awake craniotomy . The anesthetic plan should be able to cover the four stages of surgery: surgical exposure, brain mapping and functional testing, resection of the lesion, and wound closure . After surgery, the patient either returns to the neurosurgery ward or to be admitted to the postanesthetic care unit (PACU) .
Midazolam (a short-acting benzodiazepine) was used few years ago as a sedative during monitored anesthesia care in cases of awake craniotomy ,. Midazolam is the most common sedative to be used for conscious sedation owing to its rapid onset and short duration of action .
Dexmedetomidine is an α2 agonist that has eight times greater affinity for α2 receptors than clonidine with shorter half-life. It was approved as a sedative by American Food and Drug Administration in 1999 . It became an alternative to midazolam in awake craniotomy in 2001 when it was used for the first time in this field by Bekker et al . It has sedative-, analgesic-, and anesthesia-sparing effects with no suppression to ventilation which favored its use during the awake phase of craniotomy .
In our institution, dexmedetomidine was available for some time, then disappeared for nearly 1 year from our available resources and reappeared again. This brought the idea of going back to an old sedation policy using midazolam to consciously sedate the patients during awake craniotomy and compare it to dexmedetomidine. Thereby, the aim of the current study is to compare the safety and efficiency of midazolam versus dexmedetomidine when used for conscious sedation during awake craniotomy.
| Patients and methods|| |
This quasi-experimental study was conducted at Zagazig University Hospitals (Egypt) during the period from January 2015 to January 2017. After obtaining Institutional Research Board approval and fully informed written patients’ consents, 24 patients scheduled for awake craniotomy for resection of tumors related to eloquent areas were enrolled in the study. Those were all the patients who underwent awake craniotomy during the period of the study. Patients were cooperative, of both sexes, aged 21–65 years, and American Society of Anesthesiologists (ASA) grade I or II.
The inclusion criteria were useded to ensure that the patients were suitable for such technique of surgery, including the presence of supratentorial lesion based on conventional MRI, locating near or within eloquent areas. All patients were fluent in speaking and understanding without preoperative severe deficits or cognitive impairment. All the procedures in the current study were performed by the same neurosurgeon.
Exclusion criteria included patients with low Karnofsky Performance Status scale  of less than 60 (Appendix A) and cognitive impairment using Mini-Mental State Examination  score less than 24 (Appendix B), severe language deficits (>30% of naming errors despite a preoperative trial of dexamethasone and mannitol), anxious patients with State-Trait Anxiety Inventory  score of more than 55 (Appendix C), or refusal of the procedure. Patients were also excluded if there were preoperative severe motor deficits, large tumors with mass effect resulting in more than 2 cm of midline shift, tumors with dural invasion (that cause significant pain on resection), or surgeries requiring positioning other than supine or with expected operative time of more than 4 h. Patients with a BMI of more than 35, severe cardiac or respiratory disease, anticipated difficult-to-manage airway, history of allergy to LA or drugs used in the study, or known alcohol or substance abuse were excluded from the study.
For psychological preparation, both the surgeon and the anesthesia team explained to patients in the current study what he/she would experience and what they should do to cooperate as well as the expected sequelae.
No sedation was given as premedication. On arrival to the operating room nasal cannula was applied and oxygen was delivered at 3 l/min. Central intravenous line was applied and secured, then intravenous 8 mg ondansetron, 8 mg dexamethasone, and 10 mg/kg phenytoin were given (preoperative anticonvulsant therapy was necessary in patients included in this study and therapeutic serum levels were achieved days before the surgery). On the day of surgery, the morning dose of phenytoin was doubled from 5 to 10 mg/kg, then resumed on 5 mg/kg after surgery. All patients received prophylactic antibiotics. Routine monitoring was applied including ECG, noninvasive blood pressure monitoring, monitoring of oxygen saturation (SPO2), respiratory rate (RR), and end-tidal carbon dioxide measured via an end-tidal carbon dioxide nasal cannula.
All patients were placed on the operating table in the correct position for surgery using enough padding to ensure patient comfort. Then, all patients received intravenous propofol (1 mg/kg) and fentanyl (1 μg/kg) before circumferential scalp block which requires multiple injections.
Circumferential scalp block: 3–5 ml of LA (lidocaine 1% and bupivacaine 0.25% in a ratio of 1 : 1) was used to bilaterally block each of the following branches which are responsible for sensory innervations of the forehead and scalp including the supraorbital, supratrochlear, zygomaticotemporal, auriculotemporal, great auricular, greater occipital, and lesser occipital nerves. The LA dose limits are 2–3 mg/kg for bupivacaine, 5 mg/kg for lidocaine, and 7 mg/kg for lidocaine plus epinephrine ([Figure 1]).
|Figure 1 A drawing for the main branches responsible for the cutaneous sensory innervation of the forehead and scalp.|
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The circumferential scalp block was then reinforced with a field block in the region of the incision using 10 ml of LA mixture of lidocaine 1% and bupivacaine 0.25% in a ratio of 1 : 1. The sites of pin insertion were also infiltrated using 2 cm lidocaine 2% with 1 : 200 000 epinephrine.
All patients were administered propofol infusion at a rate of 1.5–4.5 mg/kg/min. It was stopped ∼15–20 min before functional brain mapping and was resumed during wound closure. Fentanyl was given 25 μg bolus every 30 min on a regular pattern.
The patients were divided into two equal groups. group D: the dexmedetomidine group (n=12) and group M: the midazolam group (n=12). The targeted level of sedation in both groups was a Ramsay sedation scale  (RSS) of 2–3 with either of the drugs used in the study during the time of cortical mapping, while before and after that the patient was kept at an RSS of 5–6 ([Table 1]).
For group D: 1 µg/kg dexmedetomidine was administered intravenously over 20 min as an initial loading dose, followed by continuous infusion of 0.1–0.7 µg/kg/h as a maintenance dose using a syringe pump. Fifteen minutes before starting cortical mapping, the dose of dexmedetomidine was reduced to 0.1 µg/kg/h. Higher levels of maintenance dose were resumed during wound closure.
For group M: midazolam was administered as an intravenous loading dose of 0.1 mg/kg given slowly over 10 min followed by a maintenance dose of 0.03–0.2 mg/kg/h using a syringe pump. Fifteen minutes before starting cortical mapping, the dose of midazolam was reduced to 0.03 mg/kg/h. Higher levels of maintenance dose were resumed during wound closure.
Ice-cold saline was always available for cortical irrigation in case of stimulation-induced intraoperative seizures. A small dose of propofol (0.5 mg/kg) was prepared to control seizures, if occurred.
Emergency airway management strategies were preprepared ensuring the availability and readiness of laryngeal mask airway, endotracheal tube, laryngoscope, fiber-optic endoscope, as well as tracheostomy kit, if to be needed. General anesthesia measures were available and ready to be performed at any time.
Urinary catheterization was avoided as it causes patient discomfort  and urinary convene was prepared to be used if needed (e.g. if diuretics were used or if surgery went too long >4 h). Since urinary catheterization was not performed, the judicious use of fluids was considered and maintenance intravenous fluids were given as normal saline at a rate of 50–100 ml/h.
All patients were transferred to the PACU when RSS=2 for 4–8 h before being transferred to the neurosurgery ward.
Data were collected by a physician who was blinded to the protocol of the study. In addition to patient characteristics and operative data, the following data were also recorded:
- Success rate of the technique based on the need to shift to general anesthesia.
- Cases of oversedation if occurred (needed >20 min after stopping all sedative infusions during cortical mapping to reach an RSS of 3=responding to commands).
- Duration of sedation starting from the first dose of propofol given to the patient until the time to stop all infusions at the end of procedure.
- Duration of recovery from sedation defined as time from stopping all infusions until the time to be ready to transfer to the PACU (RSS=2).
- Duration of surgery starting from skin incision to skin closure.
- Mean arterial blood pressure (MAP), heart rate (HR), RR, and SPO2. Data were recorded before starting sedation and then every 15 min until time of discharge to the PACU. The following definitions were encountered: hypertension (MAP ≥100 mmHg on two consecutive readings and managed according to the cause whether pain, anxiety, hypothermia, or hypoxia). Hypotension (MAP <30% of basal, managed by intravenous fluids and vasopressors if needed). Tachycardia (HR>110 beats/min and managed according to the cause whether pain, anxiety, hypothermia, or hypoxia). Bradycardia (HR<60 beats/min, managed with 0.1 mg/kg atropine sulfate and check the cause), bradypnea (RR < 12 breath/min, managed by lowering or stopping the hypnotic and/sedative), hypoxia (SPO2<92% on nasal cannula 3 l/min, managed by maintaining airway and applying noninvasive continuous positive airway pressure).
- Intraoperative complications such as nausea, seizures, airway obstruction, or respiratory depression were reported, if occurred.
- Postoperative complications were recorded, if occurred.
- Patients’ postoperative questionnaire regarding the experience of awake craniotomy was done.
- Surgeon satisfaction based on successful mapping was detected using a scale of 1–3 (3, good; 2, fair; 1, poor).
All data were collected, tabulated, and statistically analyzed using SPSS 20.0 for Windows (SPSS Inc., Chicago, Illinois, USA) and MedCalc 13 for Windows (MedCalc Software bvba, Ostend, Belgium). Quantitative data were expressed as the mean±SD. Qualitative data were expressed as number and percentage. Categorical variables were compared using χ2 test or Fisher’s exact test as appropriate. Noncategorical data were compared using unpaired t test. Risk assessment by relative risk and 95% confidence interval were done. A P value less than 0.05 was considered statistically significant; P value less than 0.001 was considered highly statistically significant; and P value more than or equal to 0.05 was considered statistically insignificant.
| Results|| |
The results obtained in the present study showed that patients’ characteristics and surgical data were comparable between both groups ([Table 2]).
Success rate was significantly higher in group M compared with group D (100 vs. 91.7%, respectively). Although the number of patients who went into deep sedation was higher in group M than group D [four (33.3%) and one (8.3%), respectively], these data were insignificant when statistically compared ([Table 3]).
|Table 3 Success rate and cases of oversedation in both groups of the study|
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Duration of surgery and duration of sedation were comparable between both group D and group M, while the duration of postoperative recovery from sedation was statistically significantly longer in group M compared with group D (24±1 vs. 18±8, respectively) as shown in [Table 4].
|Table 4 Durations of surgery, sedation, and recovery in both groups of the study|
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MAP, HR, SPO2, and RRs showed no significant differences between both groups and during all recorded times of the study. The following anticipated intraoperative complications were not recorded in either groups of the study: nausea, airway obstruction, respiratory depression, oxygen desaturation, hypertension, hypotension, tachycardia, or bradycardia. However; three (25%) cases in group D experienced intraoperative seizures, two of them were controlled by cortical irrigation using ice-cold saline, and an intravenous dose of propofol (0.5 mg/kg), while only one (8.3%) case could not be uncontrolled and awake technique was aborted, and then the surgery was resumed under general anesthesia. No postoperative complications were recorded in both groups of the study.
Postoperative patients’ questionnaire ([Table 5]) showed that all the patients in the current study understood the rationale of awake craniotomy. Thirty-three percent in eithers groups experienced great intraoperative fear sensation, while little fear was experienced by 50% of patients in group D versus 41.7% in group M, and no fear was experienced by 16.7% of patients in group D versus 25% in group M with no statistical variations between groups. Most of the patients in both groups had comfortable position (83.3% in group D vs. 91.7% in group M) with no statistical variations. All patients had memories of the procedure, 66.7% of the patients in group D recalled all intraoperative events compared with 16.7% in group M with statistically significant difference, while partial recalling occurred in 33.3% of patients in group D compared with 83.3% in group M with statistically significant difference indicating better amnestic performance of midazolam. The majority of patients in both groups described the experience as a positive experience (75 vs. 83.3% in group D and group M, respectively) with no statistical difference between groups (+ve/−ve: 9/3 in group D and 10/2 in group M).
Surgeon satisfaction score was higher in group D of the study; however, it was not statistically significant. The surgeon opinion denoted that both are acceptable techniques to be performed during awake craniotomy procedures ([Table 6]).
|Table 7 Appendix A Karnofsky Performance Status scale rating criteria (%) |
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[Figure 2] shows assessment of motor power of a patient included in the current study during the mapping and resection phases. [Figure 3] shows another patient performing different speech tasks assessment through our Arabic language speech module on a tablet screen during the mapping and resection phases.
|Figure 2 (a) MRI brain, FLAIR sequence shows the right frontal lesion related to the right motor area mostly low-grade glioma. (b, c) intraoperative photographs showing assessment of motor power during the mapping and resection phases while the patient is awake. FLAIR, fluid-attenuated inversion recovery.|
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|Figure 3 (a) MRI brain with contrast, T1 axial with contrast shows left parietotemporal lesion mostly high-grade glioma related to speech pathway especially Wernicke’s area. (b) Intraoperative photograph showing different speech tasks assessment through our Arabic language speech module on a tablet screen during the mapping and resection phases while the patient is awake.|
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| Discussion|| |
In the current study, sedation only ‘awake throughout’  technique was followed. The idea of this technique is to use variable levels of sedation according to the stage of surgery with spontaneous ventilation maintained without the use of an airway device. Sedation is deepened during certain times of surgery including: applying the Mayfield Pins, skin incision, removal of the bone flap, and dura mater. Sedation is then decreased or sometimes stopped during functional brain mapping before the resection of the lesion. Then, the level of sedation is elevated again during the stage of closure. Oversedation increases the potentialities for airway obstruction with subsequent hypercapnia and/or hypoxia, while in adequate sedation results in uncomfortable and anxious patients .
Many studies discussed the advantages of using dexmedetomidine for awake craniotomies especially the easy arousability of the patients from sedation . It was used as a loading dose of 0.5–1 μg/kg over 20 min, followed by an infusion rate of 0.2–0.7 μg/kg/h depending on the required level of sedation. During brain mapping, an infusion of 0.1–0.2 µg/kg/h is maintained ,. These doses are similar to the doses used in this study. Dexmedetomidine might cause dose-dependent hypotension and bradycardia  owing to its sympatholytic effect; therefore, close monitoring is a must. In the present study, none of the cases had bradycardia nor hypotension.
Midazolam is a benzodiazepine that can be given by multiple routes with intravenous administration providing the fastest onset of action. It has sedative, amnestic, and anxiolytic properties with no analgesia. Therefore, it is usually used with an opioid such as fentanyl . The great disadvantage of this combination is the potentiality of cardiac and respiratory depression. However, if given slowly, and in incremental doses, this drawback can be avoided . In the current study, no cases of respiratory or cardiac depression were recorded.
Manchella et al.  studied 26 patients who underwent awake craniotomy retrospectively and prospectively. Patients in that study were given total intravenous anesthesia using a combination regimen of propofol, remifentanil, and clonidine. They found that 31% of their patients had partial recall to the events of the procedure and 42% had considerable recall. These results are close to the results obtained in the dexmedetomidine group in the current study. However, patient memories were significantly lower in the midazolam group which can be attributed to their amnestic properties. In their study, Manchella et al.  reported 92% satisfaction rate by the patients with regard to the whole experience. In the present study, satisfaction rates were from75% in the dexmedetomidine group to 83.3% in the midazolam group. The lower satisfaction rates in the dexmedetomidine group was related by the patient to the occurrence of seizures.
Seizures are common intraoperative complications that usually occur during mapping of the brain in awake craniotomy ,. Conte et al.  reported that their incidence can be as high as 31% in an asleep–awake technique, and medical intervention was needed in only 7% of the patients. In their study , no benzodiazepine was included in the anesthetic regimen. In the current study, 25% of the patients in the dexmedetomidine group experienced intraoperative seizures, and only one (8.3%) case was uncontrolled and needed the shift to general anesthesia. This comes in accordance with the results obtained by Conte et al. . Another study by Danks et al.  which studied 157 patients under midazolam sedation reported a much less overall incidence of intraoperative seizures (<8%) during awake craniotomy. This variation in the incidence of seizures during awake craniotomy might be due to different levels of intraoperative electrophysiological monitoring, the intensity of the current and stimulator used, different anesthetic techniques, or the underlying pathology itself (tumor size and site, epilepsy, or tumor with epilepsy) ,. In the present study, none of the patients in the midazolam group experienced intraoperative seizures. The high incidence of intraoperative seizures in the dexmedetomidine group might be explained by the absence of benzodiazepines in that technique. It might also be attributed to the withdrawal of dexmedetomidine  during brain mapping; however, few studies are available regarding the withdrawal seizures of dexmedetomidine.
The answer to the question regarding the most suitable agent for conscious sedation has not been confirmed yet. Demiraran et al.  in their study on sedation for endoscopic procedures compared dexmedetomidine with midazolam and found the two drugs as comparable regarding hemodynamics and sedation, with statistically significantly better satisfaction scores with midazolam (84 to 90%, respectively). Moreover, another study by Kamer et al.  compared dexmedetomidine with midazolam for conscious sedation and did not detect any complications in either of the groups of the study. These results are in accordance with the results obtained in the current study. However; in contrast to the results obtained in the current study, Jalowiecki et al.  in their study compared dexmedetomidine alone versus meperidine plus midazolam and fentanyl in colonoscopies and found a statistically significant decrease in HR and MAP in the dexmedetomidine group and documented ventricular extra-systoles in one case. This difference might be due to the high number of ASA II cases (75%) in that study as well as the different surgical procedures.
Zeyneloğlu et al.  compared the recovery periods in cases of extracorporeal shock wave lithotripsy sedated with dexmedetomidine with those sedated by a combination of midazolam and fentanyl and observed longer recovery periods in the dexmedetomidine group. Kamer et al.  found no difference between the dexmedetomidine and midazolam with regard to the recovery periods. In the current study, it was found that patients in the dexmedetomidine group had more rapid recovery than those in the midazolam group. These differences between the three studies may have resulted from variations in the duration of each procedure. From this assumption, we hypothesize that time of surgery might affect the time of recovery from sedation. But this hypothesis should be supported by further studies. Midazolam itself has a rapid onset and a rapid recovery; however, the half-life of its active metabolite is long; thereby, prolonged use results in prolonged sedation .
Limitations of the study
Multiple causes led us into being a quasi-experiment sacrificing the randomization including the few number of cases of awake craniotomy performed in our institution and the unavailability of dexmedetomidine during sometimes of the study.
- One patient in the dexmedetomidine group developed uncontrolled intraoperative seizures that necessitated the shift to general anesthesia and was considered as a failed technique. The case was statistically temporarily absent from a part of the study (Group D n became 11). The case was included again in patient’s postoperative questionnaire and surgeon satisfaction score.
- The small number of population in this study is not sufficient to be conclusive about the success rate of the drug.
Conclusions and recommendation
In this study, both dexmedetomidine (used as an intravenous loading dose of 1 μg/kg over 20 min, followed by an infusion rate of 0.1–0.7 μg/kg/h, that was lowered during cortical mapping to 0.1 µg/kg/h) and midazolam (used as an intravenous loading dose of 0.1 mg/kg given slowly over 10 min followed by a maintenance dose of 0.03–0.2 mg/kg/h, lowered during cortical mapping to 0.03 mg/kg/h) provided safe and efficient conscious sedation during awake craniotomy.
Midazolam was found to have a higher success rate, the lower incidence of intraoperative seizures, amnestic behavior, and the higher rates of patients’ satisfaction. Dexmedetomidine is still a good choice for this technique due to the more rapid recovery than midazolam. Further studies are mandatory for validation and support of these results and dosage regimen.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]