|Year : 2019 | Volume
| Issue : 2 | Page : 220-227
Evaluation of intrathecal dexmedetomidine for spine surgery
Islam H Elhadary, Samah El Kenany, Hala M Elhadary, Mostafa M Saied
Department of Anesthesia, Surgical Intensive Care, and Pain Management, Faculty of Medicine, Mansoura University, Mansoura, Egypt
|Date of Submission||26-Jan-2019|
|Date of Acceptance||12-Mar-2019|
|Date of Web Publication||12-Jun-2019|
Samah El Kenany
Department of Anesthesia, Surgical Intensive Care and Pain Management, Faculty of Medicine, Mansoura University, Mansoura, 35516
Source of Support: None, Conflict of Interest: None
Background and aim Anesthesia for major lumbar spine surgeries is challenging to the anesthetist due to multiple perioperative problems and severe postoperative pain that require a tailored anesthetic technique. The aim of this study was to evaluate the effects of adding intrathecal dexmedetomidine to bupivacaine in combined spinal–general anesthesia with regard to the intraoperative hemodynamics and postoperative analgesia in patients subjected to elective major lumbar spine surgeries.
Patients and methods In this prospective, randomized, double-blind study, 62 patients were assigned to one of two equal groups: bupivacaine group (B) and dexmedetomidine group (D). Time to the first rescue analgesic request was the primary outcome. Hemodynamics, blood loss, cumulative 24 h pethidine consumption, postoperative visual analog scale pain scores, and side effects were the secondary outcomes. Student’s t-test and Mann–Whitney U-test were used. P values less than 0.05 were considered significant.
Results In group D, there was a longer time to the first postoperative opioid request (360.57±25.43 min vs. 162.00±9.33 min, P<0.001), lower total 24-h pethidine consumption (35.00±12.9 mg vs. 73.57±17.09 mg, P<0.001) and pain scores postoperatively (P<0.001), more intraoperative hypotension (P<0.05) and lower amount of blood loss (P<0.05).
Conclusion Dexmedetomidine as an intrathecal adjuvant to bupivacaine during anesthesia for major lumbar spine surgeries provides better postoperative analgesic profile (increases the analgesic duration and decreases the amount of consumed opioids), and it causes more hypotension that is easily corrected and is in favor of reduced blood loss, compared with bupivacaine alone.
Keywords: anesthesia, bupivacaine, dexmedetomidine, intrathecal, lumbar spine surgeries
|How to cite this article:|
Elhadary IH, El Kenany S, Elhadary HM, Saied MM. Evaluation of intrathecal dexmedetomidine for spine surgery. Res Opin Anesth Intensive Care 2019;6:220-7
|How to cite this URL:|
Elhadary IH, El Kenany S, Elhadary HM, Saied MM. Evaluation of intrathecal dexmedetomidine for spine surgery. Res Opin Anesth Intensive Care [serial online] 2019 [cited 2019 Oct 14];6:220-7. Available from: http://www.roaic.eg.net/text.asp?2019/6/2/220/260136
| Introduction|| |
Spinal surgeries represent a challenge to the anesthetists as they are accompanied with multiple perioperative problems including significant intraoperative blood loss and severe postoperative pain .
Extensive blood loss during spine surgery necessitates greater transfusion needs, jeopardizes the patient’s hemodynamics and can cause neurological damage because of the proximity of highly fragile neurological structures .
Postoperative pain is severe and typically lasts for 3 days. Adequate pain management is mandatory as it leads to a better functional outcome, earlier patient’s ambulation, earlier discharge, and prevents the development of chronic pain .
Different anesthetic techniques have been successfully used for lumbar spine surgeries including endotracheal general anesthesia (GA) and spinal anesthesia (SA). GA is the most commonly used anesthetic modality that is more accepted by the patients. It also enables the performance of longer surgeries and provides secured airway in the prone position .
SA reduces the blood loss and decreases the venous pressure, thus improves the surgical field, avoids positioning problems and provides better postoperative pain control .
Combining general and SA allows gaining the benefits of both techniques such as better hemodynamic stability, lower doses of the used opioid analgesics and general anesthetics, thus decreasing their side effects, better and more prolonged analgesia and improved total patients’ functional capability . However, the relatively short duration of action of the presently available local anesthetics (LAs), when used alone, makes postoperative analgesia short lived. Hence, intrathecal adjuvants may be needed to prolong the postoperative analgesia.
We hypothesized that adding intrathecal dexmedetomidine (DEX) to bupivacaine would provide better intraoperative surgical conditions and prolong the postoperative analgesia compared with bupivacaine alone. The aim of this study was to evaluate the effects of adding intrathecal DEX to bupivacaine in combined spinal-general anesthesia on intraoperative hemodynamics and postoperative analgesia in patients subjected to elective major lumbar spine surgeries. The primary outcome was the time to the first rescue analgesic request. Secondary outcome variables included the postoperative static and dynamic pain visual analog scale (VAS) scores, cumulative 24-h pethidine consumption, perioperative changes in mean arterial blood pressure (MAP) and heart rate (HR) and side effects.
| Patients and methods|| |
Following the Institutional Review Board approval (no. MS/773) and obtaining informed written consent, patients aged 20–60 years with American Society of Anesthesiologists physical status class I–II, of either sex, who were scheduled for elective major lumbar spine surgeries under combined spinal-general anesthesia were included in this prospective, randomized, controlled, double-blind study. The study was performed during the period spanning from December 2014 until April 2016. Patients suffering from cardiovascular disease, renal or hepatic disorders, patients with BMI greater than 30 kg/m2, pregnancy, those with coagulation disorders, known allergy to any drug used under protocol, presence of infection at surgical site, patients on chronic opioid therapy, receiving calcium channel blockers, and drug abusers were excluded. Patients on medications for neuropathic pain like pregabalin and gabapentin were required to discontinue them for 14 days before surgery.
A total of 62 patients were randomly allocated using a computer generated randomization sequence that was kept in closed opaque envelopes to one of two equal groups: bupivacaine group (group B) and DEX group (group D). After thorough preanesthetic evaluation, patients were instructed preoperatively on how to use a VAS for measuring pain intensity, using a horizontal line of 10 cm length (0 cm was for no pain and 10 cm was for the worst imaginable pain). Patients’ monitoring included electrocardiogram, pulse oximetry and noninvasive blood pressure measurement. Patients’ baseline vital measurements were recorded. All patients received intravenous lactated Ringer’s 7 ml/kg as coload.
Patients in both groups received combined SA–GA. SA was administered in the sitting position under complete asepsis with 25 G Quincke needle at L2–L4 interspaces using 3 ml volume containing 2 ml (10 mg) hyperbaric bupivacaine (0.5%) in both groups plus 1 ml of 0.9% saline in group B and DEX (10 µg) diluted in 1 ml 0.9% saline in group D. Thereafter patients lied down in the supine position. The intrathecal injectat was prepared in coded syringes by independent pharmacist then syringes were delivered to an anesthetist who was not aware of its content and who provided the perioperative care. Sensory anesthesia was checked with pin prick, and the modified Bromage scale was used to assess motor block . A waiting period of 20 min or time for maximal spinal action, whichever occurred earlier, was allowed to pass before GA induction.
Patients were premedicated with midazolam 0.03 mg/kg and fentanyl 1 μg/kg intravenously. Anesthesia was induced with i.v. 1.5–2.5 mg/kg propofol slowly until loss of verbal contact. Atracrium 0.5 mg/kg i.v. was given to facilitate proper placement of endotracheal tube then mechanical ventilation of the lungs aiming end-tidal carbon dioxide (ETCO2) at 30–35 mmHg was adopted.
Anesthesia was maintained with sevoflurane, vaporized in air–oxygen (40% inspired fraction) aiming to keep bispectral index values from 40 to 60, and atracurium incremental as needed. At the end of the operation, reversal of residual neuromuscular blockade was carried out by administering neostigmine 50 μg/kg and atropine 20 μg/kg intravenously. Patients were extubated after fulfilling the criteria of extubation. If intraoperative bradycardia (heart rate less than 60 beats/min) or hypotension (systolic blood pressure less than 90 mmHg) had occurred, 0.2 mg i.v. Atropine or additional 250 ml i.v. fluid bolus and/or incremental doses of ephedrine 5 mg i.v. respectively were administered. Diclofenac 75 mg was started intramuscularly/12 h at the end of the operation. Pethidine 25 mg was administered intravenously as postoperative rescue analgesia whenever VAS score was ≥4.
All surgeries were carried out by the same surgeons, and anesthesia was provided by the same anesthetists. A blinded investigator not involved in patient’s care collected the perioperative data.
The primary outcome was the time to the first rescue analgesic request. Secondary outcome variables included the postoperative pain VAS scores, both at rest (static) and on movement (dynamic), evaluated at 1, 2, 4, 8, 12, and 24 h after surgery, the cumulative 24-h pethidine consumption, the perioperative changes in MAP and HR recorded at the following times: basal (immediately before SA), every 5 min for 20 min after SA, immediately after induction of GA and thereafter every 10 min during the first 30 min and then every 30 min until the end of the operation. Then every 15 min in the postanesthesia care unit for the first postoperative hour and at 2, 4, 8, 12, and 24 h after surgery. The total intraoperative used doses of ephedrine and atropine, the volume of fluid boluses and the amount of blood loss were also recorded. Side effects such as bradycardia, sedation evaluated by modified Ramsay Sedation Scale , nausea/or vomiting, shivering and pruritus were noted and recorded.
The sample size was calculated by PASS software, version 11.0.8 [Hintze J. (2011). PASS 11; NCSS LLC, Kaysville, Utah, USA; http://www.ncss.com].
Calculation relied upon a pilot study performed by the research team on 10 participants in each group with the primary outcome was the time to the first reacue analgesic request. In this pilot study, the mean±SD was 300±15 in group D and 255±75.3 in group B (t=1.8534, two-tailed P value=0.0803).
Group sample sizes of 28 participants in each group achieve 85% power to detect a difference of 45.0 between the null hypothesis that both group means are 300.0 and the alternative hypothesis that the mean of group B is 255.0, with estimated group SDs of 15.0 and 75.3 and with a significance level (α) of 0.05000 using a two-sided two-sample t-test. We added 10% more to compensate for possible dropouts.
SPSS, version 22 (IBM; SPSS Inc., Chicago, Illinois, USA), was used for statistically analyzing the data. Data were tested for normality using the Kolmogorov–Smirnov test. Continuous data of normal distribution are presented as mean±SD and were analyzed with the Student t-test. Mann–Whitney U-test was used for analysis of the non-normally distributed data, and they are presented as median (range). Nominal data are presented with number (%) and were analyzed with the χ2-test. A P value less than 0.05 was considered statistically significant.
| Results|| |
A total of 70 patients submitted for elective major lumbar spine surgeries were assessed for eligibility. Five patients were excluded because of receiving pregabalin, three patients refused to participate in the study. Sixty-two patients completed the study ([Figure 1]).
Patients’ demographics, maximum preinduction sensory level, and the duration of the surgeries were similar in the two groups ([Table 1]).
|Table 1 Patients’ characteristics, maximum preinduction sensory level, and duration of surgery|
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Compared with the B group, the intrathecal use of DEX in group D resulted in significantly longer time to the first rescue analgesic request (360.57±25.43 vs. 162.00±9.33 min, P<0.001) and lower cumulative pethidine consumption at 24 h (35.00±12.9 vs. 73.57±17.09 mg, P<0.001) ([Table 2]), lower 1, 2, 4, and 8 h static pain scores ([Figure 2]a), and lower dynamic pain scores at 1, 2, and 4 h after surgery ([Figure 2]b).
|Table 2 Time to first analgesic request and cumulative pethidine doses in the first 24 h postoperatively|
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|Figure 2 Postoperative visual analog scale (VAS) pain scores (a) at rest and (b) during movement. Data are represented as mean±SD. *P<0.05 compared with the B group.|
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Baseline HR and MAP levels showed no significant difference among groups ([Figure 3] and [Figure 4]). Patients in the D group had significantly lower HR and MAP started 5 min after induction of SA and lasted up to 8 h postoperatively ([Figure 3] and [Figure 4]), required significantly larger volumes of crystalloids, ephedrine, and atropine and had lesser amounts of intraoperative blood loss ([Table 3]).
|Figure 3 Perioperative heart rate changes. Data are reprersented as mean±SD. *P<0.05 compared with the B group. GA, general anesthesia; PO, postoperative.|
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|Figure 4 Perioperative mean arterial blood pressure (MAP) changes. Data are represented as mean±SD. *P<0.05 compared with the B group. GA, general anesthesia; PO, postoperative.|
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Patients in the D group had more bradycardia, higher sedation score for the first postoperative hour (P<0.032) and fewer instances of shivering [2 (5.7%) versus 15 (42.9 %), P<0.001] compared to the B group. Incidence of nausea, vomiting and pruritus did not differ between the study groups ([Table 4]).
| Discussion|| |
DEX was found to be a very promising intrathecal adjuvant to LA that prolongs the postoperative analgesia and promotes its quality with lesser side effects in comparison with the most commonly used intrathecal adjuvants, opioids .
Concerning the potential neurotoxicity of intrathecal DEX, it should not be used as a sole anesthetic for neuraxial anesthesia. In a study by Konakci et al. , on rabbits, they observed that epidural DEX, when administered without LA, would induce neurotoxicity (evidence of demyelination of the oligodendrocytes in the white matter in the DEX group) in doses as high as 6.1 μg/kg. An experimental study on sheep concluded that intrathecal injection of DEX as an adjuvant to LA in the range of 2.5–100 µg did not cause neurological deficits . Abdallah and Brull  in their systematic review showed that intrathecal DEX in doses of up to 0.2–1 µg/kg did not produce any neurotoxic manifestations. Moreover, intrathecal DEX has shown a neuroprotective effect similar to methylprednisolone ,. No long-term and irreversible harmful effects have been reported yet.
We have shown that the use of intrathecal DEX combined with bupivacaine resulted in significantly longer time to the first rescue analgesic request, lower 24-h cumulative pethidine consumption, static pain scores at 1, 2, 4, and 8 h and dynamic pain scores at 1, 2, and 4 h after surgery, and lower incidence of shivering, but more bradycardia and hypotension and higher sedation score for the first postoperative hour, in comparison with those who received intrathecal bupivacaine only. There was no difference between the study groups as regards the incidence of nausea, vomiting, and pruritus.
There is no specific recommended dose of DEX as an adjuvant to LA in SA. The dose can be varied from 3 to 15 μg. Effects are usually dose dependent .
The dose of DEX used in this study was in accordance with Gupta et al.  who concluded that the addition of 10 µg to 0.5% hyperbaric bupivacaine is associated with significantly earlier onset of sensory and motor block as well as prolonged duration of sensory block, motor block and postoperative analgesia compared with 2.5 or 5 µg intrathecal DEX with a similar adverse effect profile.
Our results are consistent with the previous studies concerning the use of intrathecal DEX added to bupivacaine as regards the more prolonged analgesic duration ,,,,,,,,. Intrathecal DEX is believed to exert its analgesic effects via spinal α2 receptors by preventing the release of C-fiber neurotransmitters and by hyperpolarization of postsynaptic dorsal horn neurons .
In our study, DEX enhanced analgesia for the first 8 h at rest and for the first 4 h on movement after surgery. It also exerts opioid-sparing effect for the first 24 postoperative hours. In agreement with our results was the systematic review and meta-analysis by Wu et al.  who reported similar results.
Postsynaptic activation of α2-adrenoceptors in the central nervous system leads to a decrease in central sympathetic outflow and thus can decrease systemic blood pressure and HR . This may explain the hemodynamic changes (hypotension and bradycardia) in this study that were more pronounced in group D than in group B at most time points. This result is similar to that of Al-Ghanem et al.  who reported a decrease of HR and blood pressure with intrathecal DEX. In contrast to our results, Shukla et al.  concluded that DEX as a bupivacaine adjuvant was associated with hemodynamic stability. However, the authors of that study used DEX–bupivacaine in lower limb surgery and the sensory level was T10. In contrast also to our results, a retrospective analysis of 15 656 patients concluded that there was no significant difference in the overall incidence of intraoperative hypotension or bradycardia, despite this and similar to us, the requirement for vasopressors or atropine was more in the DEX group . Intrathecal DEX in the current study had a favorable effect on intraoperative blood loss that may be explained by the greater reduction of blood pressure with the use of DEX.
This work showed a similar incidence of postoperative nausea and vomiting in the study groups but fewer instances of pruritus with the use of DEX. This could be due to reduced pethidine consumption.
In agreement with a previous study , we could report a significantly reduced shivering incidence in the DEX group. DEX suppresses the neuronal conductance, thus decreasing the central thermosensitivity . Moreover, it restricts calcium entry into the nerve cells leading to a reduction of the release of noradrenaline from the axonal terminals in the hypothalamus .The use of intrathecal DEX in this study was found to be associated with higher sedation scores compared with the B group. In contrast to our results, Al-Mustafa et al.  did not report a significant difference of sedation score with intrathecal DEX. Presynaptic activation of the α2-adrenoceptor in the locus coeruleus inhibits the release of norepinephrine and results in the sedative and hypnotic effects . Intrathecal DEX-induced sedation may be related to its systemic absorption and vascular redistribution to higher centers or may be related to cephalad migration in the cerebrospinal fluid . Of note, the observed increased sedation score in our study was transient and confined mostly to the first postoperative hour.
This study has some limitations. First, we did not use different doses of intrathecal DEX, perhaps a lower dose could produce the same effects with fewer side effects. Second, we did not compare DEX to other commonly used adjuvants such as opioids, however, a recent meta-analysis by Sanders et al.  proved its superiority to fentanyl in this respect. Third, we did not measure surgeon and patient satisfaction with the procedure.
| Conclusion|| |
Adding DEX as an intrathecal adjuvant to bupivacaine in combined spinal–general anesthesia for major lumbar spine surgeries provided better postoperative analgesic profile (increased the postoperative analgesia duration and decreased the amount of consumed opioids with fewer side effects) and caused more hypotension that was easily corrected and was in favor of reduced blood loss, compared with intrathecal bupivacaine alone.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]