|Year : 2016 | Volume
| Issue : 3 | Page : 523-529
Intrathecal versus intravenous dexmedetomidine in characteristics of bupivacaine spinal block in lower abdominal surgery
Mohammed H Afifi1, Ashraf M Mohammed1, Sabry I Abdullah1, Khaled E Ellisy2
1 Department of Anesthesia and Intensive Care Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Anesthesia and Intensive Care Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt
|Date of Submission||24-Jun-2016|
|Date of Acceptance||04-Sep-2016|
|Date of Web Publication||23-Jan-2017|
Khaled E Ellisy
MSc, 7 Opal Court, Wexham Street, Wexham, Slough, Berkshire SL3 6LZ, UK
Source of Support: None, Conflict of Interest: None
Dexmedetomidine was shown to improve bupivacaine spinal anesthesia.
The aim of this study was to compare between intrathecal and intravenous (i.v.) dexmedetomidine as an adjuvant to bupivacaine spinal anesthesia.
Patients and methods
Sixty ASA physical status I-II aged 20-60 years scheduled for lower abdominal surgery under spinal anesthesia were assigned randomly to two groups. The intrathecal group received intrathecal 15 mg hyperbaric bupivacaine with 5.0 μg dexmedetomidine, followed by an i.v. infusion of normal saline solution during surgery. The i.v. group received intrathecal hyperbaric bupivacaine 15 mg with 0.5 ml normal saline solution, followed by a loading dose of dexmedetomidine 0.5 μg/kg over 10 min and then a maintenance dose of 0.5 μg/kg/h during surgery. Assessment parameters were vital signs, spinal block, analgesia, sedation, and side effects.
Blood pressure and heart rate values were lower in the i.v. group than in the intrathecal group. The intrathecal group had earlier sensory onset, higher peak sensory level, and prolonged sensory regression time to S1 dermatome (P < 0.001). The time to Bromage 3 motor block was comparable between both groups, but the regression time to Bromage 0 was prolonged in the intrathecal group (P < 0.001). The intrathecal group had a longer time to first analgesic request (P < 0.001) and less analgesic consumption than the i.v. group. The i.v. group had a higher intraoperative sedation level. The intrathecal group had fewer side effects than the i.v. group, but this was statistically insignificant.
As an adjuvant for spinal bupivacaine, intrathecal dexmedetomidine is superior to i.v. dexmedetomidine. It provides more stable hemodynamics, greater block augmentation, better analgesia, and fewer side effects including the intraoperative sedation score than the i.v. route.
Keywords: bupivacaine, dexmedetomidine, intravenous, spinal
|How to cite this article:|
Afifi MH, Mohammed AM, Abdullah SI, Ellisy KE. Intrathecal versus intravenous dexmedetomidine in characteristics of bupivacaine spinal block in lower abdominal surgery. Menoufia Med J 2016;29:523-9
|How to cite this URL:|
Afifi MH, Mohammed AM, Abdullah SI, Ellisy KE. Intrathecal versus intravenous dexmedetomidine in characteristics of bupivacaine spinal block in lower abdominal surgery. Menoufia Med J [serial online] 2016 [cited 2020 Feb 26];29:523-9. Available from: http://www.mmj.eg.net/text.asp?2016/29/3/523/198694
| Introduction|| |
Lower abdominal surgeries performed under regional anesthesia provide several advantages, such as spared spontaneous respiration, low cost, reduced risk of pulmonary aspiration, and elimination of the need for intubation , .
Various additives have been used to prolong the duration of spinal anesthesia and/or to enhance postoperative analgesia including agents, such as phenylephrine, epinephrine, clonidine, neostigmine, and opioids  .
Dexmedetomidine is a novel selective α2 adrenoceptor agonist primarily used for intravenous (i.v.) sedation. Dexmedetomidine has increasingly been reported to prolong the duration of local anesthetics by different routes of administration , . I.v. and intrathecal dexmedetomidine have been shown to prolong the duration of spinal anesthesia and enhance postoperative analgesia , .
| Patients and methods|| |
With the approval of the Institutional Ethical Committee of Faculty of Medicine, Menoufia University, Egypt, and after obtaining patients' written informed consent, 60 ASA physical status I-II aged 20-60 years scheduled for lower abdominal surgery with an expected duration of 90-120 min under spinal anesthesia were enrolled in this prospective randomized comparative study. Exclusion criteria were patient refusal, history of cardiac, hepatic, neurological, or renal disease, history of allergy to study drugs, any contraindication for regional anesthesia, and failed or unsatisfactory spinal block.
All patients were assigned randomly using a computer-generated randomized code into two groups: intrathecal group (n = 30) patients received intrathecal 15 mg hyperbaric bupivacaine (Marcaine 0.5%; Astra Zeneca, UK) together with 5 μg Dexmedetomidine (Precedex; Abbott; Chicago, IL, USA, 100 μg/ml diluted with normal saline solution (NSS) to 10 μg/ml), followed by an NSS i.v. bolus and an i.v. infusion of maintenance volume equivalent to that of the i.v. group throughout the entire period of the surgery. Patients in the i.v. group (n = 30) received intrathecal hyperbaric bupivacaine 15 mg together with NSS 0.5 ml, followed by an i.v. bolus dose of dexmedetomidine 0.5 μg/kg over 10 min and then an i.v. infusion of a maintenance dose of 0.5 μg/kg/h (200 μg dexmedetomidine in 2 ml added to 48 ml NSS yielded dexmedetomidine 4 μg/ml) for the entire period of surgery ([Figure 1]).
Patients were visited preoperatively for a full assessment of history, clinical examination, and revision of investigations. All patients were taught how to interpret their pain with the numerical rating pain scale (NRS) until they became familiar with its use. In the holding area, baseline vital signs were recorded [blood pressure, heart rate, oxygen saturation by pulse oximetry (SpO 2 ), and respiratory rate]. An 18-G i.v. cannula was inserted, and no premedication was administered to any of the patients. NSS (10 ml/kg) was infused over 30 min for all patients. Under a sterile technique, spinal anesthesia was carried out using a 22-G Quincke spinal needle after skin infiltration with 2% lidocaine 3 ml at the L3-L4 level, a midline approach in the sitting position, and then in the supine position. The time of spinal injection was considered time zero (T0). The i.v. drug regimen was started according to the group to which patients were assigned. Oxygen (2-4 l/min) was supplied by a nasal cannula. Monitoring included continuous ECG, noninvasive blood pressure, and pulse oximetry. The study drugs were prepared by an anesthetist who was not involved in the study, stored at room temperature in unlabeled syringes, and used within 30 min after preparation. Both the anesthetist and the postanesthesia care unit (PACU) nurse who were involved in the study were blinded to patients' groups.
Vital signs (heart rate, systolic and mean blood pressure, and SpO 2 ) were recorded at 3 min intervals intraoperatively until 15 min, every 5 min for the first hour, every 15 min until the first 3 h, and at 30 min intervals for the next 3 h. Hypotension was defined as a decrease in systolic blood pressure more than 30% from the baseline value or systolic blood pressure less than 90 mmHg. Hypotension was treated by an i.v. bolus of 10 mg ephedrine and a crystalloid bolus of 250 ml fluid over 10 min. Both were repeated if the hypotension persisted. Bradycardia was defined as heart rate less than 50 beats/min or a decrease in the heart rate more than 30% of the baseline; it was treated by 0.5 mg atropine. The need for ephedrine, atropine, and i.v. fluid consumption was recorded by time and dose.
For the assessment of sensory block, the following data were recorded: the onset of sensory block [time from T0 to the loss of pinprick sensation at the sixth thoracic dermatome (T6) level], the peak sensory level (the highest sensory block level for four consecutive tests) and its time, and the regression time to S1 [time from T0 to the regression time to the first sacral dermatome (S1) level]. Assessment was performed by loss of pinprick sensation along the mid-clavicular line bilaterally every 2 min to determine the onset (T6 dermatome); at this point, the surgery could be started. Then, the sensory level was tested every 3 min until the peak sensory level was achieved. Sensory level testing was then carried out every 15 min for the first 3 h and every 30 min thereafter until the sensory level regressed to S1. In case of a discrepancy in the dermatome level between the right and the left side, the higher level was used for statistical analysis.
Assessment of motor block was performed using the modified Bromage scale  . Bromage 0: the patient is able to move the hip, knee, and ankle; Bromage 1: the patient is unable to move the hip but able to move the knee and ankle; Bromage 2: the patient is unable to move the hip and knee but able to move the ankle; and Bromage 3: the patient is unable to move the hip, knee, and ankle. The time to reach Bromage 3 motor block was recorded before surgery and the regression time to Bromage 0 was recorded after surgery. Failure to reach the T6 sensory level or Bromage 3 motor block within 20 min from T0 was considered an unsatisfactory block and the patient was excluded from the study. Patients were discharged from the PACU after regression to S1 dermatome and Bromage 0 were achieved.
Assessment of pain was performed hourly for 12 h using a NRS 0-10 (0 = no pain, 10 = the worst pain imaginable). The patient was instructed to rate his/her pain numerically. The duration of effective analgesia was defined as the duration of NRS less than 4. When NRS score was 4 or more, patients were administered diclofenac (Voltaren, 75 mg in 3 ml; Novartis, Switzerland). (Perfalgan, 1000 mg in 100 ml; Bristol-Myers Squibb, NY, USA), i.v. infusion, to achieve NRS score less than 4. The time to first analgesic request and the total analgesic consumption for 12 h were recorded. Assessment of sedation was performed using the Ramsay sedation scale  at 15 min intervals during the surgery and every 30 min in PACU. The development of any side effects including nausea, vomiting, headache, itching, shivering, respiratory, or cardiovascular events was recorded.
The data collected were tabulated and analyzed using SPSS (version 19.0; SPSS Inc., Chicago, IL, USA). Results were expressed as means and SDs, medians and ranges, or numbers and percentages. P value less than 0.05 was considered statistically significant.
| Results|| |
The patient groups were comparable in demographic data, type of surgery, and ASA physical status (P > 0.05) ([Table 1]).
Preoperative heart rate, systolic blood pressure, and mean blood pressure in both groups were similar (P > 0.05). Blood pressure values during the first 90 min ([Figure 2]) and heart rate values during the first 60 min ([Figure 3]) were statistically significantly lower in the i.v. group than in the intrathecal group (P < 0.05). The i.v. group had a statistically higher mean consumption of atropine (0.17 vs. 0.12 mg, P = 0.037) and ephedrine (4.3 vs. 2.7 mg, P = 0.014) than the intrathecal group, but this was not clinically significant. The total i.v. fluid consumed was higher in the i.v. group than in the intrathecal group (P < 0.001) ([Table 2]), although the operation times were similar ([Table 1]). SpO 2 levels were comparable between both groups throughout the study (P > 0.05).
Spinal block characteristics
The intrathecal group had a statistically earlier sensory onset to T6 (P = 0.010), but this was not clinically significant, shorter time to peak sensory level (P < 0.001), higher median peak sensory level (P < 0.001), and prolonged sensory regression time to S1 dermatome (P < 0.001) than the i.v. group. The mean onset time to reach Bromage 3 was comparable between both groups (P = 0.606), but the regression time to Bromage 0 was statistically significantly prolonged in the intrathecal group than in the i.v. group (P < 0.001) ([Table 3]).
Analgesia, sedation, and adverse effects
The intrathecal group showed a statistically significantly lower mean 12 h NRS (P < 0.001), although not clinically significant, longer time to first analgesic request (P < 0.001), and less total analgesic consumption than the i.v. group. The mean consumption of diclofenac and paracetamol was lower in the intrathecal group than in the i.v. group (82.5 vs. 102.5 mg, P = 0.017, and 1100 vs. 1366 mg, P = 0.006, respectively). The intrathecal group showed a longer period of effective analgesia (time to NRS < 4) ([Figure 4]) than the i.v. group. The i.v. group had a higher mean 6 h Ramsay sedation scale than the intrathecal group, but this was not clinically significant (P < 0.001). I.v. dexmedetomidine provided a higher intraoperative sedation level, but this advantage was only limited to the operative time, and both routes provided a comparable sedation level in the postoperative period. The intrathecal group had fewer overall side effects than the i.v. group, but this was statistically insignificant (P > 0.05) ([Table 2]).
| Discussion|| |
In our study, intrathecal dexmedetomidine enhanced the anesthetic and analgesic properties of bupivacaine and reduced the analgesic requirement more than i.v. dexmedetomidine. This suggests that the analgesic effect of α2 agonists may occur mainly at a spinal level. The high lipophilicity of dexmedetomidine facilitates rapid absorption into the cerebrospinal fluid and binding to the spinal cord α2 adrenoceptor. Intrathecally administered dexmedetomidine has been shown to exert potent antinociceptive effects in animals , .
α2 Agonists can induce analgesia by acting at three different sites: in the brain and brainstem, spinal cord, and in peripheral tissues. At the spinal cord level, there is evidence that stimulation of α2 receptors leads to the production of analgesia by different suggested mechanisms such as activation of the descending medullospinal noradrenergic pathways, reduction of the spinal sympathetic outflow at presynaptic ganglionic sites, interaction between opioids and α2 agonists at the spinal cord level, and inhibition of substance P release in the nociceptive pathway , .
α2 Adrenoceptor agonists analgesia is mediated spinally through the activation of postsynaptic α2 receptors in the substantia gelatinosa of the spinal cord. The local anesthetics act by blocking sodium channels, whereas the α2 adrenoceptor agonist acts by binding to presynaptic C fibers and postsynaptic dorsal horn neurons. The analgesic action of intrathecal α2 adrenoceptor agonists involves depressing the release of C-fiber transmitters and hyperpolarization of postsynaptic dorsal horn neurons. Additive or synergistic effects may explain the prolongation of the sensory block when added to spinal anesthetics  .
Our results showed that the time to onset of motor block did not differ between the two groups. Moreover, in both groups, the duration of motor block was shorter than that of sensory block. This suggested that conduction of sensory nerve fiber might be inhibited more than that of motor nerve fiber by the same concentration of dexmedetomidine. This was also reported with clonidine  . Clonidine results in direct inhibition of impulse conduction in the large myelinated Aα fibers. The 50% effective concentration (EC 50 ) measured to block motor fibers is approximately four-folds that of small, unmyelinated C fibers. This could explain the shorter duration of motor block than that the sensory block  .
The potentiating mechanism of motor block by dexmedetomidine is not well understood, but it is suggested to be an additive or a synergistic effect to the local anesthetics , , interference with neuromuscular activity, or by binding of α2 agonists to motor neurons in the dorsal horn  . Yaksh  has shown that the intrathecal α2 adrenoceptor agonists can cause a dose-dependent decrease in motor strength in animals. Another proposed mechanism was that it might be caused by direct impairment of excitatory amino acid release from spinal interneurons  .
Our results showed that i.v. dexmedetomidine provided a higher intraoperative sedation level. Both routes provided a comparable sedation level in the postoperative period. This may be explained on the basis that administration of α2 agonist by an intrathecal or an epidural route provides an analgesic effect without severe sedation. This effect is because of the sparing of supraspinal CNS sites from excessive drug exposure, resulting in robust analgesia without heavy sedation  .
The lack of increase in the sedation scores observed in the intrathecal group is in agreement with previous studies that utilized 3-10 μg intrathecal dexmedetomidine ,,,. However, with the use of 15 μg intrathecal dexmedetomidine, sedation scores were significantly higher  .
The enhanced intraoperative level of sedation in the i.v. group can be explained on the basis of dexmedetomidine pharmacokinetics. The distribution half-life of dexmedetomidine is known to be 5-10 min. The termination half-life is known to be within 2-3 h. It has been reported that dexmedetomidine has linear pharmacokinetic characteristics and dose-dependent sedation effects  . This explains the improved sedation level during the operative time as dexmedetomidine infusion was stopped by the end of surgery. In studies carried out with dexmedetomidine, the intended level of sedation has been reported to be achieved at doses of 0.2-0.7 μg/kg/h  , which is consistent with our results.
In our study, the systolic and mean blood pressures, as well as heart rate were found to be significantly lower with i.v. rather than intrathecal dexmedetomidine. Intrathecal dexmedetomidine did not potentiate the effect of bupivacaine on blood pressure. These results were consistent with previous studies used intrathecal dexmedetomidine ,, . This may be explained by the mechanism by which local anesthetics affect blood pressure. Local anesthetics reduce blood pressure by decreasing the sympathetic outflow. Intrathecal dexmedetomidine did not decrease blood pressure further presumably because the sympathetic blockade produced by bupivacaine is nearly maximal. This is supported by the observation that 150 μg clonidine added to a high dose of bupivacaine (≥15 mg) did not decrease blood pressure compared with bupivacaine alone  , but when added to a small dose of bupivacaine (5 mg)  , or when used alone as a sole analgesic  , it resulted in a greater reduction in blood pressure in comparison with bupivacaine alone or saline, respectively.
Rapid or bolus i.v. administrations of dexmedetomidine were reported to produce a biphasic response in the form of sudden hypertension and bradycardia until the central sympatholytic effect dominated. We did not observe a biphasic change in this study. This might be attributed to sympathetic blockade associated with spinal anesthesia, slow administration of the loading dose, and sufficient preoperative hydration. These results were consistent with previous results  .
Bradycardia and hypotension were reported to be the most significant side effects with the use of α2 agonists, which are consistence with our trial results. Both side effects were reported in both groups, but they were more frequent in the i.v. group. However, these differences were not statistically significant as in previous studies  .
Shivering was absent in both groups in our study. The α2 adrenergic agents were reported to have an antishivering property as observed by Maroof et al  . Respiratory depression following the administration of dexmedetomidine was reported to be minimal  , which has also been validated by the results of our study. After spinal anesthesia, the incidence of nausea has been reported previously to range between 2 and 18%, whereas that of vomiting has been reported to range between 0 and 7%  ; in our study, only three patients developed nausea and one patient developed vomiting, which is in agreement with previous reports.
Although this study adds to the current knowledge on dexmedetomidine, these results have some limitations. This study is not sufficiently powered to detect significant differences in the secondary outcome variables or adverse effects, the population involved included only healthy patients, and the effects in older patients with cardiovascular comorbidities are yet to be investigated. Furthermore, the inclusion of a control group using bupivacaine only for spinal block would have added greater power to the study. Further studies that compare the effect of intrathecal and i.v. dexmedetomidine are required before the results of this study can be generalized on different types of patients, surgeries, or different age groups.
| Conclusion|| |
As an adjuvant to spinal bupivacaine, intrathecal dexmedetomidine is superior to i.v. dexmedetomidine. It provides more stable hemodynamics, greater augmentation to sensory and motor block, better quality of perioperative analgesia, lower level of sedation intraoperatively, and fewer overall side effects than the i.v. route.
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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]