Low-grade gliomas (LGGs) are cerebral neoplasms characterized by an infiltrative growth pattern and progressive transformation to a higher grade of malignancy.1 Intraoperative direct electric stimulation during awake surgery has proven to be a useful technique, enabling extensive removal while preserving functional integrity of eloquent surrounding brain structures.2-6
The asleep-awake-asleep (AAA) procedure4 is reliable7 and reproducible among institutions8 with very low rates of seizure, swelling, severe permanent deficit, and mortality. However, the need for perfect management of the airways in a lateral decubitus position leads to anesthetic contraindications7 that restrict the use of AAA. This is not a serious limitation for LGGs, which usually occur in young adults, but strongly limits the use of awake surgery for high-grade gliomas (HGGs).9
As an alternative to the AAA procedure, fully awake procedures10,11 without any sedation have been used with good onco-functional results. The major advantages of brain surgery with no asleep step are that it avoids the contraindications related to airway management in a lateral position and avoids the waking period, which usually lasts 10 to 20 minutes before the patients are fully cooperative but can sometimes be >40 minutes.7 Nevertheless, in such totally awake procedures, a lack of comfort during the opening phase, when the patient's participation is not needed, might be prejudicial for the rest of the procedure when the cooperation of the patient should be optimal to ensure reliable cognitive monitoring to determine the boundaries of the resection. To this end, the AAA procedure offers maximum comfort because the patient is asleep during the surgical opening and closure phases. Furthermore, scientific data on patients' perceptions of awake surgery (of any kind) for brain tumors generally indicate a high level of acceptance and satisfaction with the procedure. However, this satisfaction appears surprising when we contrast this result with reports of intraoperative pain (20%-44%), considerable discomfort (20%-29%), anxiety (29%), and fear (14%).8,11-13
In view of the very effective onco-functional results of awake surgery, the possibility of systematic screening for LGG and preventive treatment has recently been proposed14 and will obviously lead to a more frequent use of awake surgery. Because a traumatizing experience might be prejudicial for the quality of life and may delay the return to a normal socio-professional life, it is important to improve our management of perioperative discomfort.
In this study, we assessed the feasibility of hypnosis for awake surgery of LGG and patients' experience. Because this novel technique was developed with the aims of improving the comfort of patients during surgery and enhancing their postoperative quality of life by avoiding the traumatism created by awake surgery, we assessed the subjective experience of the procedure using validated questionnaires of perceived stress and posttraumatic stress disorder (PTSD). This is the first use of such scales to assess tolerance of awake surgery.
Between May 2011 and April 2015, all patients undergoing an awake craniotomy for resection of an LGG in our institution were offered a new hypnosedation procedure. This procedure was also proposed to 2 patients with an HGG. Perioperative data were recorded retrospectively.
Patients were given an information form and 4 questionnaires (see below) during a follow-up visit to evaluate the psychological impact of the operation.
One month before surgery, patients were hospitalized for 1 day for a complete neuropsychological assessment, functional magnetic resonance imaging, and an appointment with the anesthesiologist (E.F.). During this visit, personal contact was established, and information about the patient's habits and pastimes was collected. After that, the anesthesiologist carried out a short hypnosis session to gain the patient's approval and confidence in the method and to teach the patient how to construct a “safe place,” in other words, an imaginary place where they can feel safe and protected.
The day before surgery, a preoperative anesthetic visit was conducted without hypnosis.
Before the hypnotic trance was induced, the patients were comfortably installed in a lateral decubitus position with foam cushions. The hypnotic experience was progressively enhanced during the first steps of surgery so that each potential unpleasant or painful step was controlled (see Supplemental Digital Content 1 for a detailed description of hypnosedation, http://links.lww.com/NEU/A772; and Video, Supplemental Digital Content 2 for an illustration of the major times of a hypnosedation procedure for awake surgery of an LGG, http://links.lww.com/NEU/A773). Immediately after craniotomy and opening of the dura, alertness was assessed by the speech therapist. Cortical brain mapping was then conducted4,15,16 with the use of a bipolar stimulator with 5-mm spaced tips and a biphasic current intensity between 1.5 and 4 mA (60 Hz, 1-millisecond single-pulse phase, Nimbus, Hemodia). During the resection and stimulation of subcortical structures, the patient continued with the naming task, and the speech therapist analyzed any language disturbances. Resection was pursued until eloquent pathways were encountered around the surgical cavity, ie, resection was achieved according to functional boundaries (Figures 1 and 2).
Intraoperative times were recorded for all patients and compared with an exhaustive series of 33 patients who underwent AAA procedures in our institution between May 2004 and April 2015.
Quantitative residual tumor volume was calculated on the fluid-attenuated inversion-recovery sequence 3 months after surgery (Figure 1) or on the 3-dimensional T1 gadolinium sequence performed within 48 hours for the 2 patients with HGGs (Figure 2) with iPlan software version 3.5.0 (BrainLab, Feldkirchen, Germany).
Subjective Experience of Hypnosis
For psychological assessment of the surgery, we used the Cohen Perceived Stress Scale17,18 (PSS) and the Posttraumatic Stress Disorder Checklist Scale19,20 (PCLS). To evaluate the hypnosis experience, we used the Peritraumatic Dissociative Experience Questionnaire21,22 (PDEQ) and a fourth questionnaire specially designed by our team with the help of a psychiatrist (W.E.H.).
The PSS provides an overall (ie, nonspecific) measure of stress. A score of ≥40 is a significant indicator of pathological stress.
The PCLS is a brief self-report questionnaire evaluating the severity of the 3 main clusters of PTSD (re-experiencing, avoidance, hyperarousal). In this study, the French-validated version of the PCLS19,20 was used. A threshold score of 50 is usually attributed to probable PTSD.
Because dissociation is one of the expected effects of hypnosis, we wanted to assess its effect on the subjective experience of hypnosis and surgery. The PDEQ is a self-report inventory validated in French21 and used to assess any dissociation that may have occurred at the time of a trauma.22 Peritraumatic dissociation is known to create a psychological context in which posttraumatic symptoms may develop. A score >15 is indicative of significant dissociation.
Additionally, we designed an 11-item questionnaire to evaluate the experience of hypnosis during surgery (see Table, Supplemental Digital Content 3, http://links.lww.com/NEU/A774).
Qualitative and quantitative data were analyzed with the Pearson χ2 test and Student t test, respectively. Statistical significance level was set at P ≤.05.
A total of 43 hypnosedation procedures were successfully performed on 37 patients (6 patients underwent reoperation after regrowth of the tumor during the study). Among these 37 patients, 5 had previously been operated on under general anesthesia and 3 under the AAA procedure. During the period of the study, 11 awake procedures were performed with the AAA procedure. Of these 11 patients, 2 were not operated on with the hypnosedation procedure because they preferred the AAA procedure after both methods had been explained to them, and 3 were operated on emergently on days when the hypnotherapist was not present in the institution. For 6 patients, the hypnosedation procedure failed in the first minutes and was rapidly converted to AAA.
Assessment of the Method
Epidemiological and surgical data are summarized in Table 1. Intraoperative times of hypnosedation and AAA procedures performed in our institution are presented in Figure 3 and Table 2. No patient experienced aspiration pneumonia or hypoxemia during surgery. One patient died in the immediate postoperative period of unexplained ischemia of both middle cerebral arteries after complete removal of a right superior frontal gyrus LGG. A new permanent neurological deficit was observed in 1 patient operated on for a precentral gyrus glioma, revealed by a status epilepticus. This patient experienced numerous intraoperative seizures and prolonged postoperative dysphasia and dysgraphia. The postoperative period was uneventful in all 41 other cases.
The anesthesiologist (E.F.) assessed the effectiveness of hypnosis intraoperatively using objective trance symptoms (eye-roll sign, tingle)23 and adapted the storytelling to each patient according to his/her habits and hobbies.
For the 6 patients who did not reach a trance state, hypnosis was easily converted to AAA. The awake phase allowed in all these cases an effective brain mapping, and tumor resection was achieved with no complication.
Among the 43 hypnosedation procedures, 5 patients (12%) had focal seizures that ceased after irrigation of the brain with cold saline. Seven patients (16%) experienced nausea, and 5 (12%) experienced vomiting during or after resection.
Assessment of the Subjective Experience of Hypnosis
Among the 37 patients operated on with the hypnosedation procedure, 25 returned the questionnaires (28 evaluations because 3 patients were operated on twice during the period of the study and completed the questionnaires twice). Results of questionnaires are presented in Table 3 and Figure 4.
The PCLS revealed 1 case of PTSD. This patient was assessed by a psychiatrist after surgery but refused psychotherapy. He described the hypnotic experience with positive words and continued to use this experience in his everyday life. The PSS was pathological in 8 patients, and the PDEQ revealed a dissociation state in 17 evaluations. The 11-item questionnaire revealed that the burr hole procedure and bone flap removal were the events most frequently reported as unpleasant during opening (15 of 56 events in the entire series).
Statistical analysis did not demonstrate a correlation between unpleasant feelings during burr hole or bone flap procedures and dissociation or stress (Table 4).
In this study, we retrospectively evaluated a novel hypnosedation technique during awake surgery for cerebral gliomas in a monocentric series of 37 patients. The main findings of our study are the effectiveness of the technique, which in all cases allowed the resection of the tumor within functional boundaries, and the positive psychological impact of the technique in most of the patients.
Hypnosis is a Reliable and Reproducible Method in Awake Surgery for Gliomas
Thirty-seven patients (86%) operated on with the hypnosedation protocol experienced a hypnotic trance. This trance state was intraoperatively assessed by the hypnotherapist with objective trance symptoms (eye-roll sign, tingle).23 The PDEQ did not reveal dissociation in 11 cases, without any pejorative outcome for this subgroup. Because this questionnaire has been studied in war veterans, emergency workers, injured trauma survivors, victims of motor vehicle accidents, and victims of violent assault, we hypothesize that if surgery is not experienced as a trauma, the PDEQ cannot demonstrate the success or failure of hypnosis conversely to intraoperative trance symptoms.
In fact, we did not determine any exclusion criteria or measure hypnotic suggestibility, even though it has been shown that 45% of people score in the low range of hypnotic suggestibility.24 However, it is also known that high suggestibility is not necessary for pain to be reduced by hypnosis25 and that hypnosis is reliable and effective in surgical patients.26 Therefore, our results, by showing a very low rate of failure of hypnosis, confirm the effectiveness of hypnosis in a new surgical application, brain tumor resection, and suggest that individual hypnotizability might not be strictly stable, as stated by Piccione et al,27 but depends rather on the patient's subjective experience.28
Given these excellent results, we hypothesize that the patient's motivation facilitates hypnotic trance induction. Indeed, during awake surgery, the patients are real actors of their treatment. This of course requires taking time to explain both the procedure (ie, awake surgery and hypnosedation) and its impact on the natural course of the disease. Thus, because the aim of the medical team is to obtain not only the compliance of the patient but, most important, his/her motivation and determination, awake surgery is generally positively accepted and experienced by patients.8
Hypnosis Is an Effective Method to Attenuate Unpleasant Times During Surgery
Eight patients in our series presented a pathological score of stress on the PSS. Nonetheless, we did not find any statistical correlation with the subjective experience of hypnosis. Moreover, the sole patient who presented significant PTSD symptoms had a particularly good experience with hypnosis. Therefore, stress might be determined by the subjective experience of the disease (a premalignant brain tumor) rather than by a direct consequence of awake surgery. Although studies focusing on the satisfaction of patients during awake surgery for brain tumors reported good results mainly on the basis of intraoperative assessment of pain and stress and perioperative organizational aspects,8,10,11,13 our study is the first to propose validated questionnaires to measure stress and psychological impact during the management of a brain tumor. Therefore, these results cannot be compared with previous data in the field of brain tumors. Nevertheless, our questionnaire demonstrated (Figure 4) that most of the patients had a positive subjective experience of surgery and hypnosis. For instance, the local anesthesia of the scalp, which is by far the most painful preincision step, was the least frequently reported as unpleasant. This may indicate that the feeling of pain decreases as hypnosis goes deeper. Unfortunately, placement of the head clamp and the skin flap, burr hole, and bone flap procedures (which require pressure, require traction of the scalp, are noisy, and create vibrations, respectively) are obviously felt by the patient, even if they are not painful. This might explain why they are more often described as more unpleasant than preincision steps.
Another interesting finding is the pain felt by 3 patients during the skin closure. When the patient mentioned this pain, it was of course easy to perform a new local anesthesia. However, local anesthesia is also a painful event, especially when the skin incision is large, which is usual during awake surgery. Therefore, since our study, we systematically use ropivacain (with a longer lasting effect of 2-6 hours) and, when possible, intubate or put a laryngeal mask on the patient for the end of surgery. Indeed, because hypnosis requires a fully cooperative patient, its effect at the end of surgery is less certain as the patient tends to sleep, which unfortunately does not prevent painful waking during closure.
Finally, only 2 patients (5%) stated that they would choose not to have hypnosedation if they had to undergo a second awake surgery.
Advantages of Hypnosis Over Other Awake Procedures
The 2 most significant advantages of hypnosedation are the absence of anesthetic contraindication for awake surgery in lateral decubitus, in contrast to the AAA technique, and an immediate return to full consciousness, which allows an immediate valuable intraoperative neuropsychological testing of language, motor, and more complex cognitive functions.
Anesthesiological contraindications of awake craniotomy concern airway management while the patient is in a lateral decubitus position and the head is maintained in a rigid head clamp. In our series, no patient presented with any of the contraindications described by Deras et al.7 Nevertheless, during opening, no adverse effect was encountered. During brain mapping and surgical resection, even when the patients experienced seizures or vomiting, oxygen saturation, blood pressure, cardiac frequency, and consciousness allowed the procedure to be continued.
With regard to emergence time from anesthesia, in our experience, older patients seem to need a longer time than younger patients to emerge from anesthesia. Hypnosedation could thus be considered as a valuable option for awake surgery in older patients for both LGGs and for HGGs located close to a functional epicenter. Even though our series includes 2 patients with an HGG, further studies are needed to assess the usefulness, safety, and applicability of hypnosedation in this particular circumstance.
The main goal of surgery for the patients in our series was to achieve maximal tumor resection while avoiding the occurrence of a permanent neurological deficit. As a result, all patients were able to cooperate fully during surgery, and functional boundaries could be detected effectively by electric stimulation. Neuro-oncological results of our series are in accordance with those in the literature15 in that only 1 patient had a new permanent neurological deficit. However, 1 patient died in the immediate postoperative period of an unexplained bilateral cerebral ischemia distant from the craniotomy, even though no unusual events had occurred during surgery.
Our study focused on demonstrating the efficiency of hypnosedation and examining its advantages. Nonetheless, hypnosedation is not a trivial anesthetic technique. It requires intense involvement and long training of the whole team, including the patient. Therefore, the method we describe is limited by the necessity to work with an anesthetic team experienced in both neuro-anesthesiology and hypnotherapy.
Another limitation of our study is the absence of a control group for psychological assessment. Indeed, not only the hypnosis but also the awake procedure or the context of a brain tumor itself can potentially induce stress. Unfortunately, the low rate of recent AAA procedures in our institution (only 11 of the 39 AAA procedures were performed after May 2011) do not allow satisfactory comparison between both methods, especially because the PDEQ and our questionnaire, which are specific to dissociation and hypnosis, are not relevant for patients not undergoing hypnosedation.
Finally, the 68% response rate for the questionnaires can be considered satisfactory but might nonetheless have induced bias in statistical analyses.
Our study aims to demonstrate the reliability of hypnosis as an original alternative method for performing craniotomy, which allowed in our series an effective awake mapping for glioma resection with no negative psychological impact. Nonetheless, hypnosis does not appear to be superior to the AAA method, which remains, in our opinion, the gold standard for resection of LGGs in young adults. Because hypnosis does not suffer from the management of airways or from the potentially long waking period, ie, the 2 limitations of AAA method, it could reasonably be proposed as an alternative option for awake surgery of older populations. Nonetheless, even if hypnosis could thereby enlarge the indications of awake surgery, one should keep in mind that awake surgery also relies on good preoperative performances, so that intraoperative tasks can remain reliable during surgery. In other words, a good preoperative general condition and the absence of severe focal deficit will remain absolute prerequisites for awake surgery, whatever the anesthetic method chosen.
The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.
1. Pallud J, Blonski M, Mandonnet E, et al.. Velocity of tumor spontaneous expansion predicts long-term outcomes for diffuse low-grade gliomas. Neuro Oncol. 2013;15(5):595–606.
2. Jakola AS, Myrmel KS, Kloster R, et al.. Comparison of a strategy favoring early surgical resection vs a strategy favoring watchful waiting in low-grade gliomas. JAMA. 2012;308(18):1881–1888.
3. Soffietti R, Baumert BG, Bello L, et al.. Guidelines on management of low-grade gliomas: report of an EFNS-EANO Task Force. Eur J Neurol. 2010;17(9):1124–1133.
4. Duffau H, Peggy Gatignol ST, Mandonnet E, Capelle L, Taillandier L. Intraoperative subcortical stimulation mapping of language pathways in a consecutive series of 115 patients with grade II glioma in the left dominant hemisphere. J Neurosurg. 2008;109(3):461–471.
5. Sanai N, Mirzadeh Z, Berger MS. Functional outcome after language mapping for glioma resection. N Engl J Med. 2008;358(1):18–27.
6. De Witt Hamer PC, Robles SG, Zwinderman AH, Duffau H, Berger MS. Impact of intraoperative stimulation brain mapping on glioma surgery outcome: a meta-analysis. J Clin Oncol. 2012;30(20):2559–2565.
7. Deras P, Moulinie G, Maldonado IL, Moritz-Gasser S, Duffau H, Bertram L. Intermittent general anesthesia with controlled ventilation for asleep-awake-asleep brain surgery: a prospective series of 140 gliomas in eloquent areas. Neurosurgery. 2012;71(4):764–771.
8. Beez T, Boge K, Wager M, et al.. Tolerance of awake surgery for glioma: a prospective European Low Grade Glioma Network multicenter study. Acta Neurochir (Wien). 2013;155(7):1301–1308.
9. Hess KR, Broglio KR, Bondy ML. Adult glioma incidence trends in the United States, 1977-2000. Cancer. 2004;101(10):2293–2299.
10. Hansen E, Seemann M, Zech N, Doenitz C, Luerding R, Brawanski A. Awake craniotomies without any sedation: the awake-awake-awake technique. Acta Neurochir (Wien). 2013;155(8):1417–1424.
11. Wahab SS, Grundy PL, Weidmann C. Patient experience and satisfaction with awake craniotomy for brain tumours. Br J Neurosurg. 2011;25(5):606–613.
12. Danks RA, Rogers M, Aglio LS, Gugino LD, Black PM. Patient tolerance of craniotomy performed with the patient under local anesthesia and monitored conscious sedation. Neurosurgery. 1998;42(1):28–34; discussion 34-36.
13. Whittle IR, Midgley S, Georges H, Pringle AM, Taylor R. Patient perceptions of “awake” brain tumour surgery. Acta Neurochir (Wien). 2005;147(3):275–277; discussion 277.
14. Mandonnet E, de Witt Hamer P, Pallud J, Bauchet L, Whittle I, Duffau H. Silent diffuse low-grade glioma: toward screening and preventive treatment? Cancer. 2014;120(12):1758–1762.
15. Duffau H, Lopes M, Arthuis F, et al.. Contribution of intraoperative electrical stimulations in surgery of low grade gliomas: a comparative study between two series without (1985-96) and with (1996-2003) functional mapping in the same institution. J Neurol Neurosurg Psychiatry. 2005;76(6):845–851.
16. Vidorreta JG, Garcia R, Moritz-Gasser S, Duffau H. Double dissociation between syntactic gender and picture naming processing: a brain stimulation mapping study. Hum Brain Mapp. 2011;32(3):331–340.
17. Bellinghausen L, Collange J, Botella M, Emery JL, Albert E. Factorial validation of the French scale for perceived stress in the workplace [in French]. Sante Publique. 2009;21(4):365–373.
18. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983;24(4):385–396.
19. Ventureyra VA, Yao SN, Cottraux J, Note I, De Mey-Guillard C. The validation of the Posttraumatic Stress Disorder Checklist scale in posttraumatic stress disorder and nonclinical subjects. Psychother Psychosom. 2002;71(1):47–53.
20. Yao SN, Cottraux J, Note I, De Mey-Guillard C, Mollard E, Ventureyra V. Evaluation of post-traumatic stress disorder: validation of a measure, the PCLS [in French]. Encephale. 2003;29(3 pt 1):232–238.
21. Birmes P, Brunet A, Benoit M, et al.. Validation of the Peritraumatic Dissociative Experiences Questionnaire self-report version in two samples of French-speaking individuals exposed to trauma. Eur Psychiatry. 2005;20(2):145–151.
22. Marmar CR, Weiss DS, Schlenger WE, et al.. Peritraumatic dissociation and posttraumatic stress in male Vietnam theater veterans. Am J Psychiatry. 1994;151(6):902–907.
23. Spiegel H, Spiegel D. Trance and Treatment: Clinical Uses of Hypnosis. Vol 2nd ed, Washington, DC: American Psychiatric Pub; 2004.
24. Montgomery GH, Duhamel KN, Redd WH. A meta-analysis of hypnotically induced analgesia: how effective is hypnosis? Int J Clin Exp Hypn. 2000;48(2):138–153.
25. Milling LS. Is high hypnotic suggestibility necessary for successful hypnotic pain intervention? Curr Pain Headache Rep. 2008;12(2):98–102.
26. Montgomery GH, David D, Winkel G, Silverstein JH, Bovbjerg DH. The effectiveness of adjunctive hypnosis with surgical patients: a meta-analysis. Anesth Analg. 2002;94(6):1639–1645.
27. Piccione C, Hilgard ER, Zimbardo PG. On the degree of stability of measured hypnotizability over a 25-year period. J Pers Soc Psychol. 1989;56(2):289–295.
28. Fassler O, Lynn SJ, Knox J. Is hypnotic suggestibility a stable trait? Conscious Cogn. 2008;17(1):240–253.
The article describes a unique alternative method of sedation for awake craniotomy that can be presented as another option for patients, alongside the classic asleep-awake-asleep method, which has proven to be reasonably safe during the last decades. This work is very thoughtful and presents a good option for patients who may not be appropriate candidates for traditional techniques.
The article lacks a control group and is somewhat subjective about the benefits of hypnosedation over the classic asleep-awake-asleep method. It is also not known if hypnosedation has a different effect than the classic method in minimizing seizures and brain swelling. The questionnaires were completed years after the hypnosis/awake surgery experience; this fact makes the evaluation of the experience somewhat difficult to interpret.
This article describes a series of cases of low-grade glioma operated on at a single center in awake patients under hypnosis. The rationale offered is that some patients may not be eligible for the asleep-awake-asleep technique. The strengths of the article include the unique nature of the anesthetic technique and the detailed survey data taken postoperatively. The weaknesses are the lack of a control group and the concomitant use of both local anesthetic and narcotic pain relievers, which confounds the effects of hypnosis. I suspect that other confounding factors are related to an increase in proper preoperative counseling, excellent education regarding steps in the operation, and constant communication during the procedure. This point will limit what can be said about the usefulness of hypnosis but may demonstrate the importance of this sort of communication in awake procedures.
Another point that needs clarification is that 12% of patients vomited intraoperatively. This is higher that most series of awake craniotomy, and the cause is unclear. Besides being uncomfortable for patients and causing an airway concern, the sudden surge in brain swelling caused by either coughing or vomiting can be hazardous in open craniotomies.
This is an interesting study of using hypnosis for awake surgery for low-grade gliomas (43 procedures in 37 patients). The authors emphasize 2 theoretical benefits of hypnosis over conventional asleep-awake-asleep protocols for these cases: better airway management and reduced waking time. Reduced waking time did not ultimately affect operative time on the basis of the data obtained by the authors, but better airway management remains a reasonable hypothesized advantage of this approach. Other potential advantages of this approach such as patient satisfaction and accuracy of intraoperative tasks make this technique worthy of further study, ideally in a randomized comparative study alongside patients receiving standard anesthesia. Overall, the authors are to be commended for this innovative technique, which is clearly worthy of continued optimization and analysis.
Manish K. Aghi
San Francisco, California