| JOURNAL HOME | CME HOME | THIS MONTH | PAST ISSUES | ETOC | COLLECTIONS |
| AUTHORS | REVIEWERS | EDITORIAL BOARD | FEEDBACK | RSS | HELP |
| ||||||||||||||
| ||||||||||||||
|
|
|
|
||||||||||||
|
||||||||||||||
From the Departments of *Anesthesiology, Pediatrics, Rehabilitation Medicine, and Neurological Surgery, University of Washington, Seattle, Washington.
Address correspondence and reprint requests to Irene Rozet, MD, Assistant Professor, Harborview Medical Center, Box 359724, 325 Ninth Ave., Seattle, Washington 98104-2499. Address e-mail to i_rozet{at}hotmail.com.
 |
Abstract |
|---|
 Top Abstract IntroductionMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
-2 agonist dexmedetomidine (Dex) suggests that it may be an ideal sedative drug for deep brain stimulator (DBS) implantation. We performed a retrospective chart review of anesthesia records of patients who underwent DBS implantation from 2001 to 2004. In 2003, a clinical protocol with Dex sedation for DBS implantation was initiated. Demographic data, use of antihypertensive medication, and duration of mapping were compared between patients who received Dex (11 patients/13 procedures) and patients who did not receive any sedation (controls: 8 patients/9 procedures). There were no differences in severity of illness between the two groups. Dex provided patient comfort and surgical satisfaction with mapping in all cases, and significantly reduced the use of antihypertensive medication (54% in the Dex group, versus 100% in controls, P = 0.048). In DBS implantation, sedation with Dex did not interfere with electrophysiologic mapping, and provided hemodynamic stability and patient comfort. Routine use of Dex in these procedures may be indicated. |
Introduction |
|---|
|
TopAbstractIntroductionMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
The demands of these procedures are challenging. The role of the anesthesiologist includes 1) providing patient comfort, 2) keeping the patient responsive and cooperative for an extended period of time, 3) providing sedation, if necessary, that does not interfere with electrophysiologic brain mapping and clinical testing, and 4) managing the patient's arterial blood pressure within an accepted range to minimize the risk of intracranial bleeding. Over-sedation is potentially dangerous because of the difficulty with access to a patient's airway due to the stereotactic apparatus and positioning. Initially, the stereotactic rigid frame is applied to the patient's head under local infiltration anesthesia for magnetic resonance imaging and/or computed tomography localization. In the operating room (OR), the rigid head frame halo is anchored to the operating table in the position optimal for surgical approach, as well as for patient comfort. A crucial part of the intracranial procedure consists of localizing the area of interest with microelectrode recordings (MER) through the skull burr hole and recording of micropotentials of movement-related neurons. With macrostimulation testing of the implanted DBS electrode lead, clinical changes in intensity of tremor or rigidity are assessed by the surgical team, verifying correct localization. Consequently, one major requirement for successful brain mapping is preservation of clinical signs, such as tremor and/or rigidity, and patient cooperation. Conventional sedatives such as benzodiazepines may alter the threshold for stimulation or prevent clinical assessment of the patient. After completion of mapping and localization of the microelectrode, the patient is usually anesthetized for skin tunneling and implantation of the stimulator battery into the chest wall. Intraoperative arterial blood pressure control is also important, as a well-known complication in DBS procedures is intracerebral hemorrhage (2%–4%) (1–4), especially when MER are used (1–5). Patients with chronic arterial hypertension are considered to be at risk for such hemorrhage (5), although intraoperative hypertension might also impose a risk (5).
The -2 agonist dexmedetomidine (Dex) is a unique sedative medication, which can provide patient comfort and decrease arterial blood pressure while sparing respiratory depression, even at large doses (6). These properties make Dex a potentially ideal sedative medication for DBS implantation. Because all conventional GABA-ergic sedative drugs might ameliorate movement disorder, we had managed DBS implantation without any sedation in our institution before the introduction of Dex. In 2003, in collaboration with the attending surgeon (R.G.), we initiated a clinical protocol of using Dex for DBS implantation for Parkinson's disease. The purpose of this report is to summarize our experience with Dex sedation and to compare anesthetic management for DBS implantation before and after initiation of the Dex protocol.
|
METHODS |
|---|
|
TopAbstractIntroductionMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
Clinical Protocol with Dex
No sedation was given to patients for magnetic resonance imaging and/or computed tomography and placement of the rigid head frame halo, which was performed under local infiltration anesthesia with 0.25% bupivacaine with epinephrine 1:200,000 in the preoperative holding area. Upon the patient's arrival in the OR, standard anesthesia monitoring, including electrocardiogram, noninvasive arterial blood pressure cuff and pulse oximetry were applied, and supplemental oxygen was provided using nasal prongs. A 20-gauge catheter was placed in the radial artery for invasive arterial blood pressure monitoring. Dex was commenced with a continuous IV infusion of 0.1–0.3 mcg · kg–1 · h–1, and was increased by 0.1–0.2 mcg · kg–1 · h–1 every 10–15 min, if needed, to achieve Modified Observer Assessment of Alertness/Sedation (OAA/S) score of 4 (7). No maximal dose was considered. Antihypertensive medications were administered as needed to maintain the systolic blood pressure (SBP) < 140 mm Hg. These included labetalol, esmolol, and hydralazine according to the anesthesiologist's choice. The OAA/S score was assessed every 15 min during the first hour and every 30 min afterwards, and was maintained at a score of 4 throughout the case, particularly during brain mapping with MER and macrostimulation of the implanted DBS electrode lead, by adjusting the Dex infusion rate. After the DBS electrode lead was implanted, patients received general anesthesia for subcutaneous tunneling of the extension lead and implantation of the pulse generator subcutaneously into the chest wall. General anesthesia was induced with propofol and maintained with isoflurane or sevoflurane. The choice of airway management (laryngeal mask or endotracheal intubation) and use of muscle relaxants depended on the attending anesthesiologist's choice.
At the end of the operation, the surgeon was asked to grade the quality of brain mapping (MER) and possible interference of sedation with the assessment of the movement disorder (MD) (tremor/rigidity) as follows: 4, excellent condition (unimpaired MD); 3, good condition (unlimited brain mapping, but some possible decrease in MD with sedation); 2, tolerable (sedation needed to be discontinued for satisfactory brain mapping); 1, unsatisfactory (unable to map). At the end of the procedure, the neurophysiologist (J.S.) was asked about his satisfaction with MER (satisfactory/unsatisfactory) by assessing the "firing rate" of neurons, where firing rate of a neuron represents the neuron's response to various motor stimuli (active or passive movements).
On the first postoperative day, the patients were queried about their satisfaction with sedation by the 4-point scale: 4, comfortable, patient agreed to get the same sedation in future; 3, felt discomfort, but tolerable, patient would agree to receive it in future; 2, uncomfortable, patient preferred not to have this sedation in future; 1, absolutely intolerable, patient refused to undergo the same sedation in future.
Comparison Between the Dex and Control Group
Demographic data, medical history, intraoperative physiologic variables of SBP, heart rate (HR), respiratory rate, end-tidal CO2, oxygen saturation, use of antihypertensive medications, and duration of surgery were obtained in patients who received Dex (Dex group), and compared to that of patients who did not receive dexmedetomidine or any sedation before 2002 (control group). "Duration of mapping" was defined as time from the anesthesia start time until induction of general anesthesia for implantation of the pulse generator.
Unpaired Student's t-test, 
2 and Fisher's exact test were used for statistical comparison between the Dex and control groups, P < 0.05 was considered statistically significant.
|
RESULTS |
|---|
|
TopAbstractIntroductionMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
Effects of Dex in the Dex Group
To achieve the sedation goal of an OAA/S score of 4 with our clinical protocol, the dose of Dex was increased from 0.23 ± 0.08 to 0.48 ± 0.15 mcg · kg–1 · h–1 (range 0.3–0.8 mcg · kg–1 · h–1) by 1 h, P < 0.0006, and to 0.52 ± 0.17 (range 0.3–0.8 mcg · kg–1 · h–1) by the second hour, P < 0.0001 (Fig. 1). The dose of Dex was substantially decreased by the fourth and fifth hour of treatment to maintain the same level of sedation (Fig. 1).
|
All procedures were performed by the same surgeon (R.G.), and surgical satisfaction with sedation and mapping was rated as excellent (Grade 4) in 10 cases, and good (Grade 3) in three cases. In the first three cases, despite good cooperation from the patients (OAA/S score of 4) and preservation of tremor, Dex was arbitrarily discontinued on surgical request.
All patients expressed satisfaction with sedation. In nine cases, patients found the procedure to be comfortable and agreed to receive the same sedation in the future (Grade 4), and in four cases, the patients felt some minor discomfort, but agreed to undergo a similar procedure in the future (Grade 3). One patient experienced agitation after Dex was stopped. The patient who underwent two procedures with, as well as without, Dex found sedation with Dex comfortable (Grade 4).
By the neurophysiologist's observation (J.S.), MER was unimpaired by Dex in every case. In one patient, a bolus of Dex of 1 mcg/kg (for 10 min) was given for sedation purposes during MER. A comparison of firing rate during administration of a bolus of Dex to firing rate recorded 1 h later during continuous infusion of 0.4 mcg · kg–1 · h–1 did not reveal a difference.
No significant changes in respiratory rate or end-tidal CO2 were observed over time with Dex in 11 cases. Two patients had respiratory complications: one patient developed dyspnea, and one developed respiratory arrest. One patient with a history of obstructive sleep apnea (OSA) developed dyspnea, which was relieved with reduction of the Dex dose from 0.7 to 0.3 mcg · kg–1 · h–1. One patient experienced a respiratory arrest from choking toward the end of macrostimulation testing of the implanted DBS electrode lead. Dex infusion of 0.8 mcg · kg–1 · h–1 was stopped. Mechanical ventilation with face mask and laryngeal mask was ineffective because of the rigid stereotactic frame. After the frame was removed, the trachea was intubated, ventilation was restored, and the surgery was completed. The patient recovered without any neurologic sequelae. The respiratory arrest was considered secondary to his Parkinson's disease, although we cannot exclude an interaction between his disease and the sedative effect of Dex. However, this patient underwent a second uneventful implantation of a DBS on the contralateral side, and he was given Dex according to the same protocol.
With the Dex infusion, SBP significantly decreased from 150 ± 20 to 121 ± 16 mm Hg in 1 h (Fig. 1), but in 54% of cases boluses of antihypertensive medications (labetalol, esmolol, and hydralazine) were needed to decrease SBP to <140 mm Hg. In two of 13 cases a continuous infusion of antihypertensive medications was needed. There was no change in HR.
Based on the current series of 13 cases, the overall potential complications with the use of Dex included 1) dyspnea (1 case) and respiratory arrest (1 case), and 2) agitation upon discontinuation of Dex (1 case).
Comparison Between the Dex and Control Group
There was no difference in age, gender, medical history and severity of illness between the Dex and control group (Table 1). Use of Dex significantly decreased surgical time (duration of brain mapping and macrostimulation testing of the patient with implantation of the DBS electrode lead) (Table 1).
|
Baseline SBP was similar in both groups (Table 2). All patients in the control group needed treatment with antihypertensive medications, and in more than half of the cases (56%) a continuous infusion of antihypertensive drugs was needed (Table 2). However, the use of Dex significantly (P < 0.05) decreased the need for antihypertensive medications, especially with boluses during the first hour (Table 2). There was a trend toward a decrease in the use of a continuous infusion of antihypertensive medications with Dex, but this did not reach statistical significance (Table 2).
|
|
DISCUSSION |
|---|
|
TopAbstractIntroductionMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
As mentioned above, there are major anesthetic challenges during DBS implantations. An ideal anesthetic regimen for DBS implantation should consider patient comfort, hemodynamic stability, and respiratory sufficiency. In addition, the anesthetic goals in DBS implantation should include keeping the patient awake, cooperative, comfortable, and preserving the movement disorder as tremor for mapping purposes. Unfortunately, common 
-aminobutyric acid-ergic sedative drugs, such as propofol and midazolam, ameliorate tremor (or rigidity) and interfere with brain mapping and testing of the implanted DBS electrode lead. Moreover, these medications easily impair the level of consciousness, and may cause respiratory depression leading to disastrous complications due to difficulty with access to the airway, which is constrained by the bulky metal frame and the head fixed in the flexed position. Opioids may cause even more profound respiratory depression compared to benzodiazepines.
The pharmacologic profile of the -2 agonist Dex makes it appealing as an ideal sedative for DBS implantations, as it provides sedation, maintains hemodynamic stability (controls hypertension), and causes minimal respiratory depression, even at large doses (6,8). However, the effect of Dex on patients with movement disorders was unknown. The most important finding in our study is that Dex does not ameliorate clinical signs of Parkinson's disease, such as tremor, rigidity, and/or bradykinesia, and therefore can be safely used for sedation when preservation of movement disorder is essential for monitoring. In our case series, Dex provided comfort and satisfactory sedation for most patients. All our patients stayed awake during brain mapping and macrostimulation testing of the implanted DBS electrode lead, and the surgeon was satisfied with the patients' cooperation during mapping. During our initial learning curve, in the first three cases, Dex was discontinued on surgical request to maximize cooperation with neurological testing, despite a target OAA/S score of 4, good cooperation with the patients and preserved tremor. The well-preserved level of consciousness with Dex, which we observed in our series, is consistent with that similarly reported in a number of case series on awake craniotomy (9–12). However, when Dex infusion was given after premedication with fentanyl and midazolam, an impairment of cognitive function to a level unsatisfactory for precise cognitive testing has been observed (13).
One of the important findings in our study is the ability of Dex to decrease intraoperative use of antihypertensive medications. Systemic hypertension is a serious risk factor for intracerebral hemorrhage in DBS implantation (5). Another serious risk factor is the use of MER (1–5), which is a routine practice in our institution. In our experience, most patients develop arterial hypertension upon arrival in the OR, and often require antihypertensive treatment intraoperatively, with the concomitant risk of rebound hypertension at the end of the procedure. Our institutional policy of maintaining a SBP < 140 mm Hg intraoperatively is based on previous reports considering arterial hypertension as a major risk factor for intracerebral hemorrhage in DBS implantations (1,2,5). Reviewing the literature, there has only been one study reporting on intraoperative arterial blood pressure, and the authors suggest tight intraoperative SBP control of <140 mm Hg (2). In contrast, Gorgulho et al. (5) reported five patients who developed an intracranial hemorrhage during DBS implantation, and all five had a history of chronic arterial hypertension. However, three of five patients also had intraoperative episodes of SBP higher than 160 mm Hg, and the SBP in the other two patients reached 140 mm Hg (5). It would appear that both chronic arterial hypertension and acute intraoperative hypertension are significant risk factors for intracranial hemorrhage; therefore, the importance of hemodynamic stability in DBS implantations cannot be overemphasized. The hemodynamic stability and decrease in need of antihypertensive medications intraoperatively with Dex is a potential advantage. We did not observe any significant change in HR with Dex in our patients, which may be explained by the slower infusion rate of Dex in our protocol, compared with the study in healthy volunteers (6).
Dex has been reported to cause minimal respiratory depression in healthy volunteers and patients without respiratory diseases, and this is consistent with our present series. However, one patient with a history of OSA developed dyspnea during Dex infusion. This is not surprising, as Dex is a sedative. Although it does not cause respiratory depression, the relaxed muscle tone during sedation may result in upper airway obstruction, and Dex may provoke OSA even in patients without OSA (8). On the other hand, the case of respiratory arrest deserves discussion. As we know from studies in healthy volunteers (6,8) and in patients (14), Dex does not cause significant respiratory depression, even at a much deeper level of sedation than we used. However, the dose of Dex administered to this particular patient was larger than in other patients (0.8 mcg · kg–1 · h–1for 4 h compared to the average dose of 0.43–0.5 mcg · kg–1 · h–1 at the third and fourth hour of infusion). This patient was responsive and cooperative immediately before he stopped breathing, making it unlikely this event was secondary to Dex administration. In fact, the patient asked for suctioning to clear his throat just before he stopped breathing. Postoperatively, the patient recalled that he was choking on his own saliva. Cough due to venous air embolism as a consequence of the sitting position in DBS implantation was reported previously (15). This is a dangerous surgical complication in an awake, spontaneously breathing patient. Although Dex is not known to suppress cough reflex, we cannot exclude the possibility of venous air embolism. Examining the sequence of events in our case of respiratory arrest, we conclude that the respiratory arrest more likely could be attributed to a manifestation of his Parkinson's disease secondary to discontinuation of his usual antiparkinsonian medications (16), rather to over-sedation with Dex, although there is a potential interaction between the large-dose Dex infusion and Parkinson's disease. Moreover, our experience with both cases of respiratory complications at a larger than average dose of Dex infusion suggests that Dex infusion in doses larger than 0.6 mcg · kg–1 · h–1 should be used with caution in patients with Parkinson's disease.
We also observed that Dex significantly decreased the duration of brain mapping and macrostimulation testing of the implanted DBS electrode lead (surgical time). This may reflect the surgical leaning curve, nevertheless we believe the use of Dex is a significant contributing factor as the surgical procedure was often paused for adequate arterial blood pressure control in the control group.
Although the retrospective nature of our study and statistical drawbacks of comparison of a case series with historical controls do not allow us to draw definitive conclusions about the use of Dex for DBS implantation, we believe our case series suggests that infusion of Dex in DBS implantation can provide patient comfort and hemodynamic stability without impairment of mapping and with minimal respiratory depression. A prospective randomized trial is warranted to confirm our results.
|
Footnotes |
|---|
|
REFERENCES |
|---|
|
TopAbstractIntroductionMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
This article has been cited by other articles:
|
|
 |
|
  S. Papapetropoulos, J. R. Jagid, C. Sengun, C. Singer, and B. V. Gallo Objective monitoring of tremor and bradykinesia during DBS surgery for Parkinson disease Neurology, April 8, 2008; 70(15): 1244 - 1249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Dinsmore Anaesthesia for elective neurosurgery Br. J. Anaesth., July 1, 2007; 99(1): 68 - 74. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
