|Year : 2020 | Volume
| Issue : 2 | Page : 41-47
Effect of various analgesics combined with ropivacaine on pain, sensory-motor block and hemodynamic changes in intravenous regional anesthesia
Amirreza Modir1, Bijan Yazdi2, Esmail Moshiri2, Mehran Azami3, Amir Almasi-Hashiani4
1 Student Research Committee, Arak University of Medical Sciences, Arak, Iran
2 Department of Anesthesiology and Critical Care, Arak University of Medical Sciences, Arak, Iran
3 Department of Orthopedic Surgery, Arak University of Medical Sciences, Arak, Iran
4 Department of Epidemiology, School of Health, Arak University of Medical Sciences, Arak, Iran
|Date of Submission||04-Sep-2019|
|Date of Decision||23-Sep-2019|
|Date of Acceptance||07-Nov-2019|
|Date of Web Publication||23-Apr-2020|
Dr. Bijan Yazdi
Department of Anesthesiology and Critical Care, Arak University of Medical Sciences, Arak
Source of Support: None, Conflict of Interest: None
Background: The study addressed the compared effects of adding dexmedetomidine (DEX), ketamine (KET), neostigmine (NEO), and magnesium sulfate (MS) to ropivacaine on pain relief and hemodynamic changes in intravenous regional anesthesia (IVRA) during distal radius surgery.
Materials and Methods: This randomized, double blinded clinical trial recruited the following five groups of patients (n = 150) undergoing forearm surgery under IVRA, hospitalized at Valiasr Hospital (Arak, Iran): DEX, KET, NEO, MS, and placebo, in which ropivacaine 0.2% was used along with all the drugs. Subsequently, we measured the onset and duration of sensory motor block, pain score, arterial oxygen saturation (SaO2), mean arterial pressure (MAP), and heart rate (HR), as well as the quantity of opioid administration throughout the 24 h postoperatively.
Results: In each group, thirty patients were randomized and included in the analysis. The time to the onset of sensory motor block was shorter in the DEX group (P = 0.001) who had a longer duration of sensory motor block (P = 0.001), lower pain score at all times (P = 0.001), and the lowest opioid use (P = 0.001). There was no statistically significant difference between the five groups in terms of MAP (P = 0.148), HR (P = 0.642), and SaO2(P = 0.990), but the time trend of MAP (P = 0.001) and SaO2(P = 0.001) was statistically significant and also the interaction of time and groups was statistically significant for MAP (P = 0.001) and HR (P = 0.001).
Conclusion: DEX demonstrated the least amount of postoperative pain and opioid use, as well as a rapid onset and a longer duration of sensory motor block than other drugs used. Moreover, it could be thought to be an excellent recommendation to use as an adjuvant in IVRA.
Trial registration: Clinical trial registration number in Iranian randomized clinical trial: IRCT20141209020258N113.
Keywords: Dexmedetomidine, forearm surgeries, intravenous regional anesthesia, ketamine, magnesium sulfate, neostigmine, pain relief, ropivacaine
|How to cite this article:|
Modir A, Yazdi B, Moshiri E, Azami M, Almasi-Hashiani A. Effect of various analgesics combined with ropivacaine on pain, sensory-motor block and hemodynamic changes in intravenous regional anesthesia. Formos J Surg 2020;53:41-7
|How to cite this URL:|
Modir A, Yazdi B, Moshiri E, Azami M, Almasi-Hashiani A. Effect of various analgesics combined with ropivacaine on pain, sensory-motor block and hemodynamic changes in intravenous regional anesthesia. Formos J Surg [serial online] 2020 [cited 2020 May 28];53:41-7. Available from: http://www.e-fjs.org/text.asp?2020/53/2/41/283124
| Introduction|| |
Intravenous regional anesthesia (IVRA) was though first introduced by August Karl Gustav Bier in 1908, it is served as a simple, safe, and reliable procedure for minor surgeries, especially for the hand and forearm, and recognized as a proper, safe technique for inducing numbness and for preventing bleeding during limb surgeries. The rapid onset of anesthesia, low likelihood of failure, rapid recovery, and controllable extent of anesthesia have made this method particularly suitable for outpatient patients,, whereas its main limitations involve the development of tourniquet pain and the rapid expansion of pain following tourniquet release, especially during prolonged operations. The most serious complication from Bier block is considered to be the toxicity reaction following unexpected and accidental tourniquet release intraoperatively.
While several studies have been conducted to add certain drugs such as morphine, meperidine, magnesium sulfate (MS), fentanyl, sufentanil, clonidine, and ketamine (KET) to the local anesthetic solution to prolong analgesia duration, several studies have documented the analgesic effects of neostigmine (NEO) on various regional anesthetic approaches. Some local anesthetics are commonly used for IVRA. Lidocaine and ropivacaine have also been used as IVRA drugs, and some studies have used ropivacaine as a local anesthetic in IVRA.,
NEO is a cholinergic, acting, quaternary anticholinesterase agent, which augments acetylcholine (ACh) levels and indirectly stimulates muscarinic and nicotinic receptors. In general anesthesia, this is used to reverse the effect of nondepolarizing muscle relaxants. The onset of intravenous (IV) action is 1–2 min, and the peak action is achieved at 2–3 min, displaying an overall duration of action varying from 2.5 to 4 h. The antinociceptive effect of epidural and intrathecal NEO administration has been experimented and received by the mechanism of prevention of ACh degradation in the spinal cord. Studying how KET works and observing its analgesic effects as a nonbarbiturate IV anesthetic suggest that it can be considered as a suitable drug for Bier block. It is used as an adjunct and complementary medication along with other analgesics due to its analgesic and sedative effects. KET has a profound analgesic effect, with a function similar to that of morphine and promote mu receptors' pharmacological effects.
Magnesium is the fourth most abundant cation in the body. Magnesium sulfate has analgesic effects. These effects are primarily due to the regulation of intracellular calcium, in fact it is an antagonist of N-methyl-D-aspartate receptors. MS is an antagonist of N-methyl-D-aspartate receptors. Furthermore, calcium plays a key role in analgesia by local anesthetics, and its permeability is lessened by the anesthetics. Clinical research has indicated that calcium channel blockers may enhance the analgesic effect of anesthetics. For the reasons cited above, magnesium helps to increase the local anesthetic effect. It improves the quality of anesthesia and analgesia intravenously and intrathecally.,, Various studies have suggested that magnesium is effective in shortening the onset of block and in improving the quality and duration of anesthesia;,, hence, the importance of MS as a cost-effective drug in postoperative analgesia has been demonstrated. The effect of adding magnesium to lidocaine during IVRA has been proven in relieving tourniquet pain as well as decreasing fentanyl use.
Dexmedetomidine (DEX) is an α-2 adrenoceptor agonist with antinociceptive, sedative, and hypotensive actions, and if added, it can be effective in local anesthetics in peripheral nerve block. Diverse studies have reported its effect on prolonging the duration of sensory motor block and relieving pain., As studies revealed, each of the drugs, DEX, MS, KET, and NEO, was used in combination with lidocaine and bupivacaine, but not with ropivacaine for IVRA. We hence decided to conduct a study devoted to comparing the effect of adding DEX, KET, NEO, and MS to ropivacaine on pain relief and hemodynamic changes in IV anesthesia for forearm surgeries.
| Methods|| |
Ethical considerations and consent to participate
This article is the result of a thesis on general medicine, and it was approved by the Ethical Committee of Arak University of Medical Sciences with the code of IR.ARAKMU.REC.1397.347. Written consents were obtained from all participants after enrollment.
A double-blinded, randomized, parallel-group, single-center clinical trial was conducted. Our study followed the Consolidated Standards of Reporting Trials guidelines.
In this study, 150 patients with American Society of Anesthesiologists (ASA) physical status I and II, undergoing forearm surgery under IVRA admitted at Arak's Valiasr Hospital after obtaining informed consent, were included. Both genders, age range of 20–65 years, candidate for forearm surgery, ASA I and II, no Raynaud's disease, no sickle cell anemia, no history of sensitivity to the drugs used in the study, no cyanosis, no drug and psychotropic substances, no contraindications for IV anesthesia, no more than one fracture or surgery, no pregnancy, absence of chronic pain syndrome, and absence of neurological disorders were considered as inclusion criteria. The following criteria were considered as the exclusion criteria: duration of surgery >90 min, any reason which the IVRA needs to terminate or become ineffective intraoperatively, and duration of surgery <30 min.
After recording vital signs and arterial oxygen saturation (SaO2) for patients, two IV lines were inserted: one into the dorsal vein of the hand which underwent surgery and another into the other hand to inject crystalloid fluids. Two-mg midazolam was initially injected as premedication, and the double tourniquet was applied 3–4 cm above the target elbow. Afterward, the patient's arms were raised for 2 min to evacuate the blood followed by Esmarch bandage application. The proximal cuff of the double tourniquet was inflated to 100 mmHg above the patient's baseline systolic blood pressure, or to 250 mmHg atmospheric pressure, and the Esmarch bandage was removed.
The DEX, KET, NEO, and MS groups received 0.5 mg/kg DEX (manufactured by Exir Co, Tehran, Iran), 1-mg/kg KET (by Rotexmedica, Trittau, Germany), 500-mg NEO (Caspian Co., Rasht, Guilan, Iran), and 10-mg/kg MS 50% (Shahid Ghazi Pharmaceutical co., Tabriz, Iran) to induce IVRA. Moreover, ropivacaine 0.2% (Molteni, Florence, Italy) was used as a local anesthetic, with a volume of 35 ml (70 mg) for all groups, when the target dose of adjuvant was diluted to 5 ml by distilled water. Finally, the total volume injected in IVRA was 40 ml through the venous cannula for each patient in all groups. The control group was injected with 5-ml normal saline plus 35-ml ropivacaine 0.2% with a total volume of 40 ml through the venous cannula.
The onset of sensory block was determined with a 22G needle every 30 s (pinprick method). Patient response was examined in sensory dermatomes of the medial and dorsal antebrachial, ulnar, median, and radial nerves, and the level of motor block was assessed by requesting for bending wrist and hand fingers up and down (flexion and extension). A complete motor block is achieved when the patient cannot perform the voluntary movement of an organ. The onset of sensory block and motor block is the time elapsed from the time of administration of study drugs to achieving a complete sensory block and motor block in all dermatomes.
After completing the sensory motor block, the distal tourniquet was inflated to 250 mmHg, whereas the proximal tourniquet was deflated and surgery was proceeded. Heart rate (HR), mean arterial pressure (MAP), and SaO2 were recorded before the tourniquet application at 5, 10, 15, and 20 min every 10 min until surgery and after the tourniquet was deflated, as well as in recovery. Moreover, all cases of inadequate analgesia and failure in treatment were recorded, while another method was used to anesthetize and prepare the patient for surgery. Tourniquet was not deflated earlier than 35 min and was not inflated more than 90 min. If the duration of surgery was longer than 90 min, the patient would be under general anesthesia and excluded from the study. After the end of the surgery, the tourniquet was deflated with the alternate technique. Subsequently, we recorded the sensory recovery time (i.e., the time elapsed after tourniquet deflation until pain sensation in dermatomes by a 22G needle), the motor block recovery time (i.e., the time elapsed after tourniquet deflation until return of movement in the fingers), and the analgesic requirement time (i.e., the time elapsed after tourniquet deflation until the first time the patient needs pain relief).
The pain was measured by Visual Analog Scale (VAS) at the time of tourniquet inflation; at 15, 30, and 45 min; and then every 15 min until the end of the surgery. In the case of VAS >4, 1-mg/kg fentanyl was administered to the patient, and the time of receiving the first dose of fentanyl was recorded. The pain was recorded every 30 min to 2 h (i.e., at 30, 60, 90, and 120 min) and 6, 12, and 24 h after the tourniquet was deflated. In the postoperative period, 25 mg of intramuscular meperidine was also administered to the patient, if the VAS >4. The time and amount of drug received were recorded.
In this study using MedCalc software (MedCalc Software, Mariakerke, Belgium), considering alpha of 5%, power of 80%, and based on previous studies, the standard deviation (SD) of HR in DEX and MS groups was equal to 13.3 and 12.0, respectively, and the minimum expected clinical difference in mean HR between the two groups was 10, the required sample size in each group was 27, and because of loss to follow-up, 30 patients were selected for each group. By expanding the sample size according to the number of groups, a total of 150 individuals were included in the study.
Randomization, concealment, and blindness
A randomization sequence was determined using balanced block randomization method with block sizes of 5 and 10 and remained with the epidemiologist's colleague. Randomization sequence was maintained by methodologist and at the time of the study, the participants were randomly assigned to the target group. Because of the balanced block randomization method, it was not possible to predict the next ones by researchers, and thus the concealment was observed.
With regard to blinding, interventional drugs were administered by an anesthesiologist, whereas examining the interested outcomes and recording of data were performed by a senior medical student who was unaware of the groupings. In addition, patients were not aware of the administered intervention drugs.
Intention-to-treat approach was used for data analysis. The mean (SD) and frequency (percentage) were used to describe the continuous and categorical variables. One-way ANOVA with Bonferroni post hoc and likelihood ratio Chi-square test were used to compare the continuous and categorical variables between the groups, respectively. To compare the interested outcomes among groups over time, repeated-measures ANOVA was used. All statistical analyses were done using Stata, version 13 (Stata Corp, College Station, TX, USA) at significance level <0.05.
| Results|| |
This double-blinded trial recruited five randomized groups of patients undergoing forearm surgery under IVRA (n = 150). Totally, 243 patients were assessed for eligibility and 93 patients had not met the inclusion criteria and among them, 150 cases were included. Thirty patients were randomly assigned to each group, and all of them received the interventions and included in the analysis. No cases were lost and excluded after randomization.
The study was performed in 2018–2019, and the study lasted for 8 months from November 2018 till June 2019. Patient demographics and clinical characteristics at baseline were compared and are displayed in [Table 1]. Fifty percent of patients were male, and their mean age was 37.3 (SD: 10.1) years.
|Table 1: Patient demographics and clinical characteristics at baseline (n=30)|
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Based on [Table 2], a statistically significant difference was observed in sensory block among the five groups (P = 0.001). Time to onset of sensory block was shorter in the DEX group than that of other groups followed by KET, MS, NEO, and control group, and it was significantly longer in control group compared to others (P = 0.001) and also, there was a significant difference between DEX and NEO groups (P = 0.013). Duration of sensory block was longer in the DEX group followed by KET, MS, NEO, and control groups. It was statistically significantly shorter in control group compared to others (P = 0.001) and also, there was a significant difference between DEX and NEO groups (P = 0.001), DEX and MS groups (P = 0.002), and KET and NEO groups (P = 0.001). Based on [Table 2], a statistically significant difference was found in the motor block among the five groups (P = 0.001). The time to achieve motor block was higher in the control group than that in the other groups, and there was no significant difference between the other groups. The duration of the motor block was higher in the DEX group, and there was a significant difference between all groups except between MS and NEO (P = 0.299) and MS and KET (P = 0.058) groups.
|Table 2: Comparison of mean (standard deviation) of sensory and motor blocks in the five groups (n=30)|
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As shown in [Table 3] and [Figure 1], in terms of pain score measured by VAS, repeated-measures ANOVA revealed that there was a statistically significant difference between groups (P = 0.001), and the time trend of VAS, as well as the interaction of time and groups (P = 0.001) was statistically significant. The obtained evidences suggested that the lowest mean of VAS was observed in the DEX group followed by KET, MS, NEO, and control groups. The mean VAS increases with time; in the MS and control groups, this increase occurs with a steeper slope.
|Table 3: Comparison of mean (standard deviation) of pain score in the five groups (n=30)|
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There was no statistically significant difference between the five groups in terms of MAP (P = 0.148), HR (P = 0.642), and SaO2(P = 0.990), but the time trend of MAP (P = 0.001) and SaO2(P = 0.001) was significant and also the interaction of time and groups was statistically significant for MAP (P = 0.001) and HR (P = 0.001).
In terms of opioid use, the results showed a statistically significant difference among the five intervention groups (likelihood ratio Chi-square [df = 8] =88.4727, P = 0.001), among which the DEX group exhibited the lowest opioid use and the control group exhibited the highest opioid use [Table 4].
|Table 4: Comparison of frequency of opioid (pethidine) consumed in the five groups (n=30)|
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Comparison of the need for pethidine administration at different times within the first 24 h after surgery is summarized in [Table 5], In the DEX group, the onset of pethidine use was late, but in the control group, it was both faster and more common (P = 0.001).
|Table 5: Comparison of the need for opioid administration (pethidine) at different times within 24 h after surgery (n=30)|
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| Discussion|| |
This double-blind clinical trial enrolled the following five randomized groups of patients undergoing forearm surgery: DEX, KET, MS, NEO, and control groups. The distribution of patients in terms of age, gender, BP, HR, and SaO2 was similar at baseline, which means that randomization generates five exchangeable groups at baseline.
The time to onset of sensory block was shorter in the DEX group, whereas the duration of sensory block was longer in this group than that of other groups. The DEX group had a shorter time to achieve motor block and longer duration of motor block, whose pain scores were lower at all times, followed by KET, MS, NEO, and control groups. Patients in the DEX group exhibited the lowest opioid use.
As results showed, DEX group exhibited the least amount of pain and opioid use following forearm surgery, as well as the short onset and long duration of sensory motor block. DEX has been identified as the active enantiomer (S) of medetomidine. It is a highly selective alpha 2-adrenergic agonist, is an imidazole derivate, and is soluble in water. In the operating room, it may be used as an adjunct to general anesthesia or by providing sedation during regional anesthesia or during optical fiber tracheal intubation in an awake patient. The need for inhalational and IV anesthetics decreased when we performed IV injection of an initial dose of 0.5–1 μg/kg DEX within 10–15 min during general anesthesia and after infusion to 0.2–0.7 μg/kg DEX. Patients may be affected by DEX-induced sedation postoperatively and may also benefit from analgesic effects without reducing respiratory depression. DEX reduces the opioid use intraoperatively and improves pain scores; however, no analgesic benefit has been seen in all settings.
Modir et al. conducted a study to compare the effects of ketorolac/lidocaine versus DEX/lidocaine in IVRA, reporting a lower pain after three-step injection in the ketorolac and DEX groups than the lidocaine group and lower pain scores in the ketorolac group at all times after tourniquet release, whereas the score was lower in the DEX group among all the groups in our study, and they had a longer duration of sensory motor block. The study by Palak et al. aimed at comparing the effect of DEX and KET as an adjuvant to 40-ml lignocaine 0.5% for IVRA and suggested that DEX produces more sedation and that both drugs, DEX and KET, provide excellent postoperative analgesia without any side effects. Their results were consistent with those of our study.
Kumar et al. in their randomized clinical study on 72 cases of hand surgery suggested that addition of 1 μg/kg DEX or 0.5 mg/kg KET to lignocaine improves the quality of anesthesia (satisfaction score) and preoperative analgesia and also reduces sensory and motor block onset times in IVRA. In another clinical study by Singh et al. which was conducted on sixty patients of IVRA in upper limb surgery, the authors concluded that 0.2% ropivacaine and 0.5% lignocaine are equally effective, but as ropivacaine prolongs postoperative analgesia, its use is more recommended.
Nasr and Waly performed a study comparing lidocaine–tramadol and lidocaine–DEX for IVRA, reporting that sensory motor block started faster in the tramadol and DEX groups and lasted longer and that postoperative pain and opioid use were lower in the tramadol and DEX groups than in the control group, whereas no difference was found between the groups. Similarly, DEX relieved pain and prolonged the duration of sensory motor block in our study. Sethi andWason conducted a study aimed at using lidocaine and NEO in IV anesthesia for upper extremity surgeries and inferred that NEO speeds the onset of sensory motor block and relieves postoperative pain, whereas in our study, it relieved pain and prolonged the duration of sensory motor block compared to the control group, but overall, the DEX had the best effect.
In the study by Kang et al. to evaluate the effects of adding NEO to ropivacaine intravenously, the authors reported that adding NEO would relieve pain and shorten the onset of sensory block and prolong the duration of motor block, whereas in our study, it relieved pain and prolonged the duration of sensory motor block compared to the control group.
It is recommended to conduct a study in a large scale with different doses to find the best combination of drugs in surgeries. Because of relatively small sample size in this study, a multicentric trial with a larger sample size at different conditions is recommended. One of the strengths and novelties of this study is comparing five different drugs simultaneously with no cases of loss to follow-up.
As one of the study limitations, cardiotoxicity is one of the main side effects of ropivacaine, and its widespread use for IVRA is limited by this potential. In addition, tinnitus and dizziness are reported complications of ropivacaine IVRA, but we did not record the incidence of these complications.
| Conclusion|| |
DEX had the least amount of pain and opioid use after surgery, as well as the rapid onset of the sensory motor block and the longer duration of the sensory motor block than the other drugs used, and hence it could be a potential adjuvant for IVRA.
We would like to sincerely thank the Clinical Research Council at Valiasr Hospital for its guidance and the research deputy of Arak University of Medical Sciences for his assistance and support. In addition, we would like to thank all patients who were included in the study.
Financial support and sponsorship
This study was funded by Arak University of Medical Sciences.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]