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      Comparison of the Post-Caesarean Analgesic Effect of Adding Dexmedetomidine to Paracetamol and Ketorolac: A Randomized Clinical Trial

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          Abstract

          Background

          Paracetamol and non-steroidal anti-inflammatory drugs (e.g. ketorolac) can be considered for mild to moderate post-caesarean pain. As a selective α-2 agonist adrenergic receptor, dexmedetomidine has analgesic and sedative effects without causing respiratory depression.

          Objectives

          This study aimed to evaluate the effects of adding dexmedetomidine to paracetamol or ketorolac on post-caesarean pain and the associated complications thereof.

          Methods

          Sixty pregnant women, who were candidates for caesarean section with spinal anesthesia, were randomly assigned to either of two groups of 30 patients. For post-operative pain management, an intravenous patient-controlled analgesia (PCA) device was used for 24 hours. Dexmedetomidine (3 µg kg -1) was added to paracetamol (35 mg kg -1) in the group DP and to ketorolac (1 mg kg -1) in the group DK. Visual analog scale (VAS), Ramsay sedation scale, hemodynamic changes, rescue analgesic (meperidine) consumption, patient satisfaction, and possible complications were recorded at 6, 12, and 24, hours after surgery, and compared afterward.

          Results

          The pain score was significantly lower in the DK group than in the DP group (P < 0.05). The hemodynamics and sedation scale were similar in both groups. The total meperidine consumption was higher in the DP group, but it was not significantly different. Maternal satisfaction was greater in the DK group (P < 0.05). Concerning complications, the two groups did not show statistically significant differences (P = 0.4).

          Conclusions

          The addition of dexmedetomidine to ketorolac, compared with its addition to paracetamol, causes further reduction in the post-operative pain score and provides more satisfaction.

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          Most cited references31

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          The effects of increasing plasma concentrations of dexmedetomidine in humans.

          This study determined the responses to increasing plasma concentrations of dexmedetomidine in humans. Ten healthy men (20-27 yr) provided informed consent and were monitored (underwent electrocardiography, measured arterial, central venous [CVP] and pulmonary artery [PAP] pressures, cardiac output, oxygen saturation, end-tidal carbon dioxide [ETCO2], respiration, blood gas, and catecholamines). Hemodynamic measurements, blood sampling, and psychometric, cold pressor, and baroreflex tests were performed at rest and during sequential 40-min intravenous target infusions of dexmedetomidine (0.5, 0.8, 1.2, 2.0, 3.2, 5.0, and 8.0 ng/ml; baroreflex testing only at 0.5 and 0.8 ng/ml). The initial dose of dexmedetomidine decreased catecholamines 45-76% and eliminated the norepinephrine increase that was seen during the cold pressor test. Catecholamine suppression persisted in subsequent infusions. The first two doses of dexmedetomidine increased sedation 38 and 65%, and lowered mean arterial pressure by 13%, but did not change central venous pressure or pulmonary artery pressure. Subsequent higher doses increased sedation, all pressures, and calculated vascular resistance, and resulted in significant decreases in heart rate, cardiac output, and stroke volume. Recall and recognition decreased at a dose of more than 0.7 ng/ml. The pain rating and mean arterial pressure increase to cold pressor test progressively diminished as the dexmedetomidine dose increased. The baroreflex heart rate slowing as a result of phenylephrine challenge was potentiated at both doses of dexmedetomidine. Respiratory variables were minimally changed during infusions, whereas acid-base was unchanged. Increasing concentrations of dexmedetomidine in humans resulted in progressive increases in sedation and analgesia, decreases in heart rate, cardiac output, and memory. A biphasic (low, then high) dose-response relation for mean arterial pressure, pulmonary arterial pressure, and vascular resistances, and an attenuation of the cold pressor response also were observed.
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            COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression.

            Two cyclooxygenase isozymes, COX-1 and -2, are known to catalyze the rate-limiting step of prostaglandin synthesis and are the targets of nonsteroidal antiinflammatory drugs. Here we describe a third distinct COX isozyme, COX-3, as well as two smaller COX-1-derived proteins (partial COX-1 or PCOX-1 proteins). COX-3 and one of the PCOX-1 proteins (PCOX-1a) are made from the COX-1 gene but retain intron 1 in their mRNAs. PCOX-1 proteins additionally contain an in-frame deletion of exons 5-8 of the COX-1 mRNA. COX-3 and PCOX mRNAs are expressed in canine cerebral cortex and in lesser amounts in other tissues analyzed. In human, COX-3 mRNA is expressed as an approximately 5.2-kb transcript and is most abundant in cerebral cortex and heart. Intron 1 is conserved in length and in sequence in mammalian COX-1 genes. This intron contains an ORF that introduces an insertion of 30-34 aa, depending on the mammalian species, into the hydrophobic signal peptide that directs COX-1 into the lumen of the endoplasmic reticulum and nuclear envelope. COX-3 and PCOX-1a are expressed efficiently in insect cells as membrane-bound proteins. The signal peptide is not cleaved from either protein and both proteins are glycosylated. COX-3, but not PCOX-1a, possesses glycosylation-dependent cyclooxygenase activity. Comparison of canine COX-3 activity with murine COX-1 and -2 demonstrates that this enzyme is selectively inhibited by analgesic/antipyretic drugs such as acetaminophen, phenacetin, antipyrine, and dipyrone, and is potently inhibited by some nonsteroidal antiinflammatory drugs. Thus, inhibition of COX-3 could represent a primary central mechanism by which these drugs decrease pain and possibly fever.
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              Postoperative pain management

              The practice of modern anesthesiology has been developed from intraoperative period into perioperative period. Postoperative pain management is one of the most important components of adequate post-surgical patients care. This article wrote with the aim of emphasis on importance and effectiveness of post-operative pain management. Reading this article is beneficial for physicians, interventional pain managers and who care about pain medicine. Unrelieved acute pain after surgery usually elicits pathophysiologic neural alterations, including not only peripheral but also central sensitization which evolves into chronic pain syndromes. The main purpose of perioperative pain control is providing an adequate comfort level and acceptable side effects for patients. Effective postoperative analgesia improves patients’ outcome as observed by early ambulation, decrease in side effects, and reduce the incidence of postoperative chronic pain (1-3) Even though postoperative pain management and its implications have gained a significant attention in health care during last three decades, it continues to be a major challenge that still remains disregarded (4, 5). Postoperative analgesia has traditionally been provided by administration of opioid analgesics. However, excessive opioids administration is associated with a variety of side effects including ventilatory depression, drowsiness and sedation, nausea and vomiting, pruritus, ileus, urinary retention, and constipation. Prescription of multi-modal analgesic regimens contains non-opioid analgesics (e.g., local anesthetics, nonsteroidal anti-inflammatory drugs, cyclooxygenase inhibitors, acetaminophen, ketamine, clonidine, dexmedetomodine, gabapentin) as supplement of opioid analgesics can provide better postoperative pain management outcome. The opioid-sparing effects of these compounds may lead to reduced side effects of opioids (6). Nowadays variety of new drugs, analgesic techniques and devices, and preventive approaches are available for anesthesiologists, including patient-controlled analgesia (PCA), multimodal analgesia and pre-emptive analgesia. Besides, one of the most common methods for postoperative pain relief is PCA. This device is commonly assumed to imply on-demand intermittent, intravenous administration of opioids under patient control (with or without a continuous background infusion). PCA device is based on the use of a sophisticated microprocessor-controlled infusion pump that delivers a preprogrammed dosage of opioid analgesics when the patient pushes a demand button. Grass presented a more enlightened concept of PCA, noting that using any analgesic drugs under control of patient by any routes could be categorized as PCA, like patient-controlled epidural analgesia (PCEA) and patient-controlled regional analgesia (PCRA) (7). He proposed practical guidelines for the clinical usage of PCA, highlighted the complications and their management. To optimize the management of acute postoperative pain, basic mechanisms of postoperative pain must be explored and new treatments must continue to be developed. Tissue damages during surgery leads to two alterations in the responsiveness of the nociceptive system, peripheral sensitization and central sensitization. Pharmacological and non-pharmacological postoperative pain management should be started quickly to suppress the development of both peripheral and central sensitization, which involves both the primary afferent nociceptors and spinal dorsal horn neurons. Understanding the neuropharmacology of the spinal cord gives us the unbelievable opportunity to base clinical management on identified mechanisms of pain receptors, pathways, and mechanisms of action. Furthermore, evidence-based practice guidelines have the potential to provide valuable information to physicians and their patients. These guidelines not only provide guidance in routine practice, but they provide the “standard of care” for the specialists. Practice guidelines for anesthesiology and pain medicine must be improved by experts in these fields using the best available data obtained from a comprehensive review of the peer-reviewed medical literature.Anesthesiology and Pain Medicine, the official journal of Iranian Society of Regional Anesthesia and Pain Medicine (ISRAPM), aims at publishing of the scientific articles submitted by all the researchers and professionals in the field of anesthesiology and pain medicine from all over the world. It would be our pleasure to take our new steps toward medical excellence.
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                Author and article information

                Contributors
                Journal
                Anesth Pain Med
                Anesth Pain Med
                10.5812/aapm
                Kowsar
                Anesthesiology and Pain Medicine
                Kowsar
                2228-7523
                2228-7531
                31 October 2018
                October 2018
                : 8
                : 5
                : e85311
                Affiliations
                [1 ]Pain Research Center, Iran University of Medical Sciences, Tehran, Iran
                [2 ]Rasoul Akram Hospital, Clinical Research Development Center, Iran University of Medical Sciences, Tehran, Iran
                [3 ]Department of Anesthesiology and Pain Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
                Author notes
                [* ]Corresponding Author: Professor, MD, FIPP, Pain Research Center, Iran University of Medical Sciences, Tehran, Iran. Eamil: farnadimani@ 123456yahoo.com
                [** ]Corresponding Author: Pain Fellowship, Pain Research Center, Iran University of Medical Sciences, Tehran, Iran. Email: snowruzina@ 123456yahoo.com
                Article
                10.5812/aapm.85311
                6252045
                30538943
                e05ba875-8424-47eb-bbc5-dc600157c387
                Copyright © 2018, Author(s)

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

                History
                : 13 October 2018
                : 30 October 2018
                : 31 October 2018
                Categories
                Research Article

                analgesia,caesarean section,dexmedetomidine,ketorolac,paracetamol

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