|Year : 2016 | Volume
| Issue : 4 | Page : 179-187
Dexamethasone versus paracetamol in the augmentation of lidocaine in intravenous regional anesthesia in upper limb surgeries
Ibrahim T Ibrahim1, Sahar A Hashish1, Haidy S Mansour2, Mina M Raouf2
1 Anesthesiology and Intensive Care Unit, Faculty of Medicine, Minia University; Anesthesia Department, Minia University Hospital, Minia, Egypt
2 Anesthesiology and Intensive Care Unit, Faculty of Medicine, Minia University, Minia, Egypt
|Date of Submission||27-May-2016|
|Date of Acceptance||22-Oct-2016|
|Date of Web Publication||16-Dec-2016|
Haidy S Mansour
Anesthesia Department, Minia University Hospital, Minia
Source of Support: None, Conflict of Interest: None
In this study, we compare the effect of dexamethasone and paracetamol when added to intravenous regional anesthesia (IVRA) on intraoperative and postoperative analgesia, sensory and motor block onset times, sensory and motor recovery times, and tourniquet pain.
Patients and methods
Sixty adult patients undergoing elective surgical operations on the upper limb were randomly and blindly divided into three groups. All groups received IVRA lidocaine 3 mg/kg diluted with saline to a total volume of 40 ml. Group 1 received lidocaine diluted with normal saline, group 2 received lidocaine and dexamethasone 8 mg admixture, and group 3 received lidocaine and 300 mg paracetamol. All patients were assessed as regards hemodynamics, O2 saturation, respiratory rate, intraoperative degree of analgesia, and onset of sensory anesthesia and motor block. After tourniquet deflation, time to recovery of sensory and motor block and the time to first analgesic requirement were assessed.
The onset of sensory motor block occurred significantly earlier in group 2, followed by group 3 when compared with group 1. Patients in groups 2 and 3 tolerated tourniquet pain much better compared with group 1 patients. This led to prolonged time to first request for intraoperative analgesia and reduced the number of patients requiring fentanyl. As regards postoperative pain, patients in group 2 followed by group 3 patients tolerated the pain much better compared with group 1. This led to prolonged time to first request for analgesia.
Addition of dexamethasone to lidocaine in IVRA is superior to the addition of paracetamol.
Keywords: dexamethasone, intraoperative pain, intravenous regional anesthesia, paracetamol, postoperative pain
|How to cite this article:|
Ibrahim IT, Hashish SA, Mansour HS, Raouf MM. Dexamethasone versus paracetamol in the augmentation of lidocaine in intravenous regional anesthesia in upper limb surgeries. Res Opin Anesth Intensive Care 2016;3:179-87
|How to cite this URL:|
Ibrahim IT, Hashish SA, Mansour HS, Raouf MM. Dexamethasone versus paracetamol in the augmentation of lidocaine in intravenous regional anesthesia in upper limb surgeries. Res Opin Anesth Intensive Care [serial online] 2016 [cited 2020 Jun 4];3:179-87. Available from: http://www.roaic.eg.net/text.asp?2016/3/4/179/195877
| Introduction|| |
Intravenous regional anesthesia (IVRA) is a method of producing anesthesia in a part of a limb with intravenous injection of a local anesthetic into an extremity isolated from the rest of the systemic circulation with a tourniquet to avoid the effects of general anesthesia and upper airway instrumentation. It produces a rapid onset of anesthesia and skeletal muscle relaxation .
The ideal anesthetic agent for IVRA would be the one that has the required degree of local anesthetic activity, but with low cardiovascular and central nervous system toxicity. Lidocaine 0.5% is probably the local anesthetic most commonly chosen for this technique, because it is characterized by a rapid onset of action and topical anesthetic activity and intermediate duration of activity .
For producers of longer duration, tourniquet pain is a limiting factor. It has been suggested that tourniquet pain may arise from ischemia of peripheral neurons or nociceptors distal to the tourniquet or from nerve fiber activation directly under it. Moreover, mechanical trauma and tissue ischemia under or distal to the tourniquet lead to the release of inflammatory mediators and thus to tourniquet pain .
Several agents have been used as adjuvant to local anesthetics used in IVRA in an attempt to improve tourniquet tolerance, postoperative analgesia, and reduce the amount of local anesthetic used such as opioids including morphine, fentanyl , clonidine , ketorolac , muscle relaxants such as cisatracurium , ketamine , neostigmine , alkalinization by bicarbonate , nitroglycerine  and dexamethasone .
Dexamethasone should theoretically be beneficial in the management of acute surgical pain as a result of its potent anti-inflammatory effect . It has been reported that bupivacaine combined with dexamethasone prolongs the duration of analgesia in nerve blocks .
Paracetamol possesses very little anti-inflammatory activity, and studies suggest the possibility that the site of action of its antinociceptive effect may be in the central nervous system . However, several studies have demonstrated the peripheral antinociceptive properties of perfalgan (10 mg/ml; Bristol Myers Squibb, France) as an injectable paracetamol solution and was introduced into clinical practice in 2002 ,.
The objective of this randomized clinical trial was to evaluate the effect of both dexamethasone and paracetamol when added to lidocaine in IVRA and compare their anesthetic and analgesic effects in upper limb surgeries.
| Patients and methods|| |
This study was conducted during the period from January 2011 to January 2012 after obtaining approval of the local Ethics Committee of El-Minia University Hospital and informed written consent from all patients. This study included 60 adult patients of either sex between 18 and 60 years of age of ASA physical status I–II undergoing elective and emergency hand and forearm surgeries under IVRA with expected surgical times less than 90 min.
Patients with Reynaud disease, sickle cell anemia, and a history of allergy to any drug used were excluded from the study. Patients were randomized to three groups with 20 patients in each. A randomization list was generated, and identical syringes containing each drug were prepared by an anesthesiologist assistant not involved in the study.
Once the patients were transferred to the operating room, mean arterial blood pressure, peripheral oxygen saturation (SpO2, and heart rate were monitored throughout the surgical procedure as well as during the first 3 h postoperatively.
Before setting up the anesthetic block, two cannulae were placed: one was placed in a vein on the dorsum of the operative hand and the other in the contralateral hand for crystalloid infusion. The operative arm was raised for 3 min and then exsanguinated with an Esmarch bandage. A pneumatic tourniquet was left all around the upper arm, and the proximal cuff was inflated to 250 mmHg. Circulatory isolation of the arm was confirmed with inspection, lack of radial pulse and failure of pulse oximetry tracing of the ipsilateral index finger.
IVRA was accomplished using 2% lidocaine 3 mg/kg (maximum 200 mg diluted with 0.9% saline to 40 ml) in group 1 (n=20), 2% lidocaine 3 mg/kg (maximum 200 mg+8 mg dexamethasone (Sigmatec; Pharmaceutical Industries, Egypt) diluted with 0.9% saline to 40 ml in group 2 (n=20), and 2% lidocaine 3 mg/kg (maximum 200 mg+300 mg of paracetamol (perfalgan 10 mg/ml); USBA Labs/Bristol Myers Squibb in the group 3 (n=20). The mixture was introduced in more than 90 s by an anesthesiologist blinded to the injected drug.
The times for tourniquet and drug administration were recorded, sensory block was assessed every 30 s, and the onset of sensory block was evaluated using the pin prick method using a 22-G short beveled needle taken out at dermatomal distribution of the ulnar nerve (hypothenar eminence), the median nerve (thenar eminence), and the radial nerve (first web space). Onset of sensory block was defined as a decrease from baseline; complete sensory block was achieved when there was no pain sensation at the surgical site.
Moreover, motor block was assessed every minute and the onset of motor block was evaluated by asking the patient to flex and extend the wrist and fingers. Onset of motor block was defined as a decrease from baseline; complete motor block was achieved when no voluntary movement was possible.
After sensory block was achieved, distal cuff was inflated 100 mmHg above preoperative systolic pressure and proximal tourniquet was deflated and the operation was started. Tourniquet pain was assessed using visual analogue scale (VAS) (0=no pain and 10=worst pain) ,. It was monitored at 0, 5, 10, 20, 40, and 60 min and fentanyl 1 U/kg was given if VAS was greater than 3. Onset of both surgical and tourniquet pain was recorded and total fentanyl requirements were also recorded.
At the end of the surgery, tourniquet deflation was performed using the cyclic deflation technique (tourniquet was deflated three times in a cyclic manner with 10 s of deflation separated by 1 min of reinflation). The tourniquet was not deflated before 30 min.
The patient was shifted to the PACU for 3 h and then the patient was discharged to ward. Evaluation of postoperative pain was completed on the basis of the VAS. Mean arterial blood pressure, heart rate, and VAS values, time, number of patients, and total amount of diclofenac (75 mg intramuscular) were recorded.
Throughout the study period, any local or systemic complications including nausea, vomiting, skin rash, tachycardia, bradycardia, hypotension, hypertension, headache, dizziness, tinnitus, hypoxemia, sedation, respiratory depression, bradypnea, tachypnea, and other side effects were noted.
Sample size estimation showed that ∼18 patients were needed in each group to detect a clinically relevant reduction in fentanyl consumption by 25% with a power of 0.80 and a level of significance of 5%. Data were analyzed using SPSS for Windows software version 13 (SPSS Inc., Chicago, Illinois, USA). Quantitative data were presented as mean±SD, whereas qualitative data were presented as frequency distribution. The χ2, Kruksal–Wallis, and Mann–Whitney tests were used to test the significant differences in qualitative (noncategoric data in between the studied groups), whereas the analysis of variance test and the post-hoc test were used to test the significant difference in quantitative data between the studied groups. The paired t-test was used to test the follow-up of quantitative data in each group. Probability of less than 0.05 was considered as a cutoff value for significance.
| Results|| |
Sixty patients (20 in each group) were recruited for the study. Two patients received general anesthesia due to failure of the block and were excluded because of surgical complications. These patients were replaced by new patients to standardize the number of patients in each group.
The patient’s characteristics did not differ among the four groups ([Table 1]).
|Table 1: Characteristics of patients and operative data in the three groups|
Click here to view
There was a state of hemodynamic stability in the three groups throughout the study period, although there were some statistically significant differences within or between the groups observed at some times that did not affect clinical stability and did not need any interference ([Figure 1] and [Figure 2]).
There was no significant difference observed in either respiratory rate (cycle/min) ([Figure 3]) or in O2 saturation (%) ([Figure 4]) inside each group or between the three groups during the study period.
Changes in sensory and motor block
The onset of sensory blockade in group 1 took more time until sensory block started to occur in contrast to group 2 and group 3, which showed a more rapid onset of sensory block ([Table 2]).
|Table 2: Comparison of the mean±SD of the onset and recovery times of sensory and motor block (min)|
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The time to recovery from sensory block was longer in group 2 followed by group 3, whereas it was the earliest in group 1, in which sensory block faded away after tourniquet deflation.
Group 2 showed enhanced onset of motor block after injection, followed by group 3 and lastly group 1.
Tourniquet pain (visual analogue scale and intraoperative analgesia)
There was a statistically significant increase in the VAS scores ([Figure 5]) for tourniquet pain ([Table 3]) at 10 and 60 min between group 1 and group 2 after tourniquet inflation (P=0.001 and 0.003), respectively.
Moreover, there was a statistically significant increase in the VAS scores for tourniquet pain at 5 and 10 min between group 1 and group 3 (P=0.01 and 0.001), respectively. There was a statistically significant difference in the VAS scores for tourniquet pain at 5 min between group 2 and group 3 (P=0.03).
Postoperative pain scores are presented in [Figure 6] and postoperative analgesic requirements are presented in [Table 4].
There was a statistically significant difference in the VAS scores postoperatively at 10, 90, 120 min, and 6 h between group 1 and group 2 (P=0.001, 0.009, 0.001, and 0.01), respectively. Moreover, there was a statistically significant difference in the VAS scores postoperatively at 10 min between group 1 and group 3 (P=0.009). There was a statistically significant difference in the VAS scores postoperatively at 90 and 120 min between group 2 and group 3 (P=0.002 and 0.001), respectively.
Complications were only noticed as nausea in three groups, two in group 1, one in group 2, and two in group 3, and were not associated with any hemodynamic compromise.
| Discussion|| |
IVRA is a safe, easy-to-administer, reliable, and cost-effective method for short operative procedures (<1 h of the extremities performed on ambulatory procedures). IVRA can be used for manipulations in forearm and hand minor surgeries (repair of tendon injury and repair of finger tip) ,.
Mechanism of IVRA is through local anesthetic diffusion pathway from nerve mantle (outer surface to the nerve core. Mantle fibers are the first to be anesthetized (supplying proximal structures), whereas core fibers are the last to be anesthetized (supplying more distal anatomy explaining why anesthesia starts first proximally and then spreads to the distal structures) .
The ideal IVRA solution should have the following features: rapid onset, reduced dose of local anesthesia, reduced tourniquet pain, and prolonged postdeflation analgesia with high therapeutic index (low potentiality for cardiovascular and central nervous system toxicity). At present, this may be achieved with the addition of an adjuvant to local anesthetics .
However, there are some disadvantages of IVRA, including delayed onset of action, poor muscle relaxation, lack of analgesia, and local anesthetic toxicity. IVRA does not provide effective tourniquet tolerance and postoperative analgesia after tourniquet deflation. The various components of IVRA – that is, ischemia, tourniquet compression, and the presence of high concentrations of local anesthesia in the blood vessels of the extremity – may affect hemostatic mechanisms .
Additives such as opioids (pethidine), clonidine (α2-agonist), NSAIDs, neostigmine, sodium bicarbonate, and muscle relaxants (atracurium) have been added as adjuncts to local anesthetics for IVRA, in attempts to improve intraoperative anesthesia and postoperative analgesia .
This current study was designed to evaluate the effect of adding dexamethasone (8 mg) versus paracetamol (300 mg) to lidocaine 2% in IVRA in hand and forearm surgeries.
As regards the hemodynamic and respiratory changes during our study, there was clinical stability observed in these variables throughout the study period, although there was some swing in these parameters that was statistically significant in some reported times. These changes may be due to tourniquet pain or the effect of surgical stimulation on the sympathetic system. These changes did not need any interference.
In our study, there was a rapid onset of action and delayed recovery from the effect of local anesthetic, with better results observed in the dexamethasone group followed by the paracetamol group and the control group.
Our results are in agreement with a previous study  that included 60 patients scheduled for hand surgeries who were randomly allocated to three groups of 20 patients each. In group 1, IVRA was achieved with 3 mg/kg lidocaine diluted with normal saline to a total of 40 ml. In group 2, IVRA was achieved with 3 mg/kg lidocaine+300 mg of paracetamol diluted with normal saline to a total of 40 ml. In group 3, IVRA was achieved with 3 mg/kg of lidocaine and 300 mg of paracetamol intravenously immediately after injection of IVRA medication. Their study is more or less in agreement with our study in reporting that the onset of sensory block in group 1 was 7±3 min, whereas that in group 2 was 5±2 min, and the sensory block recovery time in group 1 was 5±3 min, whereas that in group 2 was 8±2 min.
As regards the onset of motor block, it was 12±4 and 8±4 min in group 1 and group 2, respectively. The motor recovery time was 6±2 and 8±4 min in group 1 and group 2, respectively. Their results stated that there was no significant difference in the onset of sensory block among the two groups (groups 2 and 3). This result may be attributed to the presence of peroxidase enzyme in cases of tissue injury (surgical trauma), which inactivates paracetamol and relative acidic pH of lidocaine and paracetamol together impeding their penetration through nerve sheath .
In a study  on patients who were candidates for elective hand and forearm surgeries, they were randomly allocated to three groups each of 25 patients. In group L, IVRA was achieved with 2% lidocaine 3 mg/kg (maximum 200 mg and 2 ml of NaCl 0.9% intravenously in the nonsurgical arm, whereas in group LD IVRA was achieved with 2% lidocaine 3 mg/kg and 8 mg dexamethasone and 2 ml of NaCl 0.9% intravenously in the nonsurgical arm. In group LDc, IVRA was achieved with 2% lidocaine 3 mg/kg and 8 mg dexamethasone intravenously in the nonsurgical arm. In all groups, 0.9% saline was added for a total volume of 40 ml. They found that sensory recovery time was delayed after tourniquet deflation in groups LD, L, and LDc with median values 12 (6.11–19.4 min), 7 (5.21–10.30 min), and 6 (4.2–8.11 min), respectively. In the same manner, the motor recovery time was delayed in group LD followed by groups L and LDc, with median values 13 (6.76–20.19 min, 8 (5.91–10.08 min, and 6 (4.44–8.43 min), respectively. In contrast to our results, they reported that the onset of sensory block was similar among the three groups, with median ranges of 2 (2.03–3.8 min), 4 (2.97–5.34 min), and 3 (2.97–4.70 min) in groups LD, L, and LDc, respectively. Moreover, they found that the onset time of motor block was similar among the groups as the median ranges were 4 (3.11–5.04 min), 5 (3.38–7.12 min), and 4 (3.33–5.06 min) in groups LD, L, and LDc, respectively.
In a study by Ko et al. , 60 patients of ASA physical status I or II between 17 and 60 years of age who were scheduled for surgery of the hand or the forearm were included in this study. The patients were randomly assigned to three groups: group C, in which patients received 0.5% lidocaine diluted with 0.9% normal saline to a total volume of 40 ml; group P, in which patients received 0.5% lidocaine diluted with intravenous acetaminophen 300 mg (perfalgan 30 ml to a total volume of 40 ml); and group K, in which patients received 0.5% lidocaine diluted with 0.9 normal saline plus ketorolac 10 mg to a total volume of 40 ml. In their study, there was no statistical difference as regards hemodynamic and respiratory data among the groups. As regards the onset of sensory loss in their study, it was shortened in group P with a mean value of 2.3±1.4 min when compared with group C with a mean value of 3.6±1.6 min. This result is due to the antinociceptive effect of acetaminophen at the peripheral site. Thus, this result is in agreement with ours. In contrast, there was no significant difference between the two groups as regards sensory recovery time as it was 3±2 and 2.6±1 min in group C and group P, respectively.
As regards tourniquet pain, our study showed that patients of group 2 were much tolerant to tourniquet, with pain scores less than those of group 3 and group 1. The maximum values of VAS in group 2 were observed at 40 and 60 min after tourniquet inflation, with mean values of 2.1±0.6 and 2.1±0.4, respectively.
In the same way, the maximum values of VAS in group 3 were observed at 20, 40, and 60 min with mean values of 2.1±1.1, 1.9±0.7, and 2.3±0.3, respectively. Patients of group 1 showed higher pain score variables during operative time with maximum mean values at 10, 20, 40, and 60 min being 3±1.2, 2.2±0.6, 2.1±0.3, and 2.6±0.7, respectively.
Moreover, the first fentanyl requirement time was delayed in patients of group 2, followed by group 3 and lastly patients of group 1 who were first to request for fentanyl injection intraoperatively with mean values of 40±0, 24±8.9, and 11.5±3.7 min, respectively. Similarly, the number of patients who needed fentanyl in group 2 was only two (10%), whereas in group 1 it was 13 patients (65%), but in group 3 there were only five patients (25%) who required intraoperative fentanyl. In this study, there were significant differences in total amount of fentanyl consumption among the three groups for intraoperative fentanyl consumption in group 1, group 2, and group 3 being 47.75±5.5, 7.75±2.5, and 17±8.2 μg, respectively.
This current study is in agreement with a previous study by Huseyin et al. , who reported that intraoperative VAS scores were decreased at 20 and 30 min in group 2, which were 0.2±1 and 0.2±1, respectively, when compared with group 1, which were 1.8±2 and 1.8±2, respectively. Moreover, they stated that the time to first fentanyl requirement was delayed in group 2 (25±5 min) when compared with group 1 (15.4±5.6 min). Similarly, they found that the number of patients who needed fentanyl in group 2 was only three (15%) and lesser compared with group 1 in which the number was 13 (65%). Moreover, they found that the total amount of fentanyl consumed in group 2 was 58±14 μg and was much lesser compared with group 1, in which the total amount was 78±12 μg.
Ko et al.  demonstrated that the time elapsed until the first analgesia requirement by fentanyl was longer in group P (paracetamol) (34.6±7.8 min) when compared with group C (control) (26.4±10.7 min). Moreover, in their study, the number of patients who required fentanyl was eight (40% in group P and11 (55% in group C. There was no significant difference among the groups for total amount of fentanyl consumed intraoperatively due to tourniquet pain in group C, which was 35.3±33.1 and was 22±28.7 μg in group P. This may be attributed to the increase in the number of patients who received fentanyl.
As regards postoperative VAS, patients of group 2 showed better pain score values throughout the postoperative period except at 120 min when VAS was 3.8±0.3, whereas patients of group 1 showed higher levels in pain score and observed early in the postoperative period at 10 min, 90 min, and 12 h after tourniquet deflation, with a mean VAS value of 3.1±0.7, 3.4±0.8, and 3.1±0.6, respectively. Group 3 showed less pain score values postoperatively compared with group 1. The maximum values were recorded at 90 min and 12 h, with a mean value of 3.5±0.9 and 3.1±0.4, respectively.
The result of the present study showed that postoperative analgesia was significant between the three groups as regards time to first request, total amount of consumption, and number of patients who received diclofenac. Patients of group 1 were first to request for diclofenac injection, followed by patients of group 3 and lastly group 2 patients who were the last to request for analgesia, with mean times of 65.9±19.4, 99.6±10.03, and 126.7±18.2 min, respectively.
As regards the number of patients who required diclofenac, it showed that all patients (100%) of the three groups had received diclofenac once, whereas 13 patients (65%) in group 1, two (10%) in group 2, and five patients (25%) in group 3 received a second dose of diclofenac (75 mg) intramuscular. Similarly, the least diclofenac consumption was observed in group 2 patients, followed by group 3 patients and group 1 patients, with mean values of 82.25±27.42, 90±30.77, and 97.5±22.5 mg, respectively.
Ko et al.  had reported that postoperative VAS score was lower in group P (2.2±1.6) compared with group C (3.8±2.4). They reported that the number of patients who needed postoperative analgesia was four patients (20%) in group P and 12 (60%) in group C. Moreover, they reported that the analgesic consumption was lower in group P compared with group C, with mean values 10±20.5 and 30±25.1 mg, respectively.
Zekiye et al.  had reported that postoperative VAS scores were lower in group LD (lidocaine+dexamethazone) than in the other group (P=0.001). As regards the number of patients who needed postoperative analgesic (diclofenac), there were 18 patients (72%) in group L (lidocaine), nine patients (36% in group LD, and 15 patients (60%) in group LDc (control). As regards total amount of postoperative analgesic, it was less in group LD (200±285 mg) but in group L it was 520±390 mg and in group LDc it was 420±445 mg. All these results are in agreement with our results. As regards the time to first request for analgesia (paracetamol in their study, it was shorter in group LD (60.9±55.5 min) when compared with group L (265.8±226.7) min and group LDc (264±186.2 min). Thus, this result is not in agreement with our results. This might be attributed to the local irritation effect of adding dexamethasone .
Moreover, Huseyin et al.  had reported that all groups had received diclofenac 75 mg once (100%), but 15 patients (75%) received a second dose in group 1 and four patients (20%) in group 2. As regards the total amount of diclofenac, it was less in group 2 (64±56 mg) when compared with group 1 (120±75 mg). Thus, this result is in agreement with our results.
In contrast to our study, Huseyin et al.  demonstrated that postoperative VAS scores were similar among groups and the time to first request for diclofenac in their study was similar among group 1 (89±62 min) and group 2 (94±110 min). These results may be attributed to the administration of diclofenac when VAS scores were at least 4, whereas administration of diclofenac when VAS was greater than 3.
As regards complications during our study, complications were only noticed as nausea in two patients in group 1, in one patient in group 2, and two patients in group 3 and were not associated with any hemodynamic compromise. Complications were noticed as nausea in a previous study  in two patients in group 1 and three patients in group 2, which did not require any interference.
All above-mentioned results (improved tourniquet tolerance, stable pain scores intraoperatively and postoperatively, less number of patients receiving fentanyl, evident postoperative analgesia, and less analgesic consumption) in both adjuvant groups (dexamethasone and paracetamol) can be attributed to the fact that dexamethasone has an analgesic, anti-inflammatory effect, and opioid-sparing action through multiple mechanisms, of which the most prominent ones are anti-inflammatory action and immunosuppressive action preventing the formation of arachidonic acid derivatives, especially leukotrienes and interleukins (ILK), which have a proinflammatory action (ILK-2, ILK-6, and ILK-12), prostaglandins (PGF2α and PGD2), oxygen free radicals (OH, H2O2), and tumor necrosis factor-α; all of them are potent inflammatory mediators that participate in pain receptor modulation . Dexamethasone also stabilizes neutrophils, macrophages, and lysosomal membranes preventing chemotaxis and their endothelial adhesion and neutrophil recruitment, decreasing cellular injury with subsequent decrease in the release of inflammatory mediators (neurokinins, substance P, calcitonin gene-related peptide, and glutamate . It also prevents the synthesis of recently discovered heat shock proteins (HSP70, which are found in cellular stressful conditions (surgical trauma), which whenever found increases intracellular Ca influx with complement activation cascade and tissue injury . Paracetamol is acting mainly on central rather than peripheral cyclooxygenase (COX-2), which is found in cases of cellular injury, thus preventing the formation of inflammatory mediators, especially leukotrienes and ILK, which have proinflammatory action (ILK-2, ILK-6, and ILK-12) mediating cellular injury . Paracetamol also modulates the endogenous cannabinoid system. It was shown that paracetamol is converted to N-arachidonoyphenolamine, or AMA404, a compound known as endogenous cannabinoid, which inhibits the uptake of vanilloid-anandamide by pain neurons resulting in analgesia. This activity was proven through the induction of a CB1 receptor antagonist, which resulted in the reversal of the analgesic action of paracetamol .
Paracetamol is metabolized into compound AMA404, which inhibits the uptake of endogenous cannabinoid by pain receptors. This molecule possesses a Na channel blocking activity, which in turn has a membrane stabilizing activity decreasing the release of acetylcholine at motor end plate leading to muscle relaxation .
| Conclusion|| |
Dexamethasone seems to be superior compared with paracetamol in providing faster sensory and motor onset times, prolonged sensory and motor blockade recovery time, more tolerance to tourniquet compression, and decreased the number of patients who needed intraoperative fentanyl. In addition, dexamethasone is more efficient compared with paracetamol in providing analgesia postoperatively evident by less total amount of diclofenac and less frequent administration.
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Conflicts of interest
There is no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4]