Opioid Epidemic: Cellular & Molecular Anesthesia as a Key Solution

Ali Dabbagh

Journal of Cellular & Molecular Anesthesia, Vol. 2 No. 4 (2017), 11 December 2017 , Page 147-148

Opioids are one of the most important arsenals armamentarium of physicians for fighting against pain. During the decades, opioids have been used in a wide range of indications; both for treatment of acute and chronic pain; as natural and synthetic compounds and in a variety of delivery forms from intravenous infusion to intrathecal adjuvants of local anesthetics or as transdermal patches. There is no doubt that we are in an opioid misuse epidemic status; whether in the US or other countries; but if we want to resolve this miserable multilateral complication, there is no doubt that Cellular and Molecular aspects of Anesthesia has a key role in resolving the problem; through creating an opioid free pain management era.

Original Articles

Background: Osteoarthritis (OA) is now considered as an active complex of biomechanical, biochemical and cellular processes, not a mere degenerative disorder. Considering the complications of common treatments of OA, including non-steroidal anti-inflammatory drug (NSAIDs) and corticosteroids, establishment of new treatments is crucial. This study aimed to explore the effect of Malva Neglecta extract on the main inflammatory biomarkers in OA.

Materials and Methods: Aqueous extract of Malva Neglecta, ibuprofen and betamethasone were prepared to investigate their effects on inflammatory biomarkers. Synoviocytes were obtained from the healthy radiocarpal joint cartilage of an 8-month-old Holstein cow. Human monocyte/macrophage (THP-1) cells were also obtained to investigate the effect of Malva neglecta extract on inflammatory agents. Lipopolysaccharide (LPS) was used to induce production of inflammatory cytokines in both cells. Real-time PCR was used to investigate the effect of Malva Neglecta extract on expression profile of TNF-α, IL-1β, COX-2, IL-18 and iNOS. Production of NO and PGE2 was also investigated in THP-1 cells.

Results: Malva Neglecta extract reduced TNF-α, IL-1β, iNOS, IL-18 and COX-2 expression in synoviocytes. Expression of all of these factors was also reduced by the extract in THP-1 cells. Moreover, production of PGE2 and NO in the LPS-induced THP-1 cells was reduced by Malva neglecta extract. Ibuprofen and betamethasone were more effective in reducing inflammatory agents than the extract.

Conclusion: According to Malva’s ability to reduce the pro-inflammatory cytokines in the synoviocytes and THP-1 cells, its potential role as a supplement method to common NSAIDs and corticosteroids was confirmed.

Comparing the use of Memantine with Dextromethorphan and Placebo to Reduce Pain before Orthopedic Surgery

Mehrdad Taheri, Alireza Mirkheshti, Alireza Manafi Rasi, Yalda Adili

Journal of Cellular & Molecular Anesthesia, Vol. 2 No. 4 (2017), 11 December 2017 , Page 157-164

Introduction: To compare the use of Memantine with Dextromethorphan and placebo to reduce pain after orthopedic surgery.

Materials and Methods: The present study was a double-blind clinical trial including180 patients undergoing elective orthopedic surgery of the lower limbs. Patients were divided randomly into three groups of 60 patients each. The first group (Group M) received 30 mg Memantine orally, the second group (Group D) received 45 mg of Dextromethorphan and the third group (Group P) received only placebo, two and a half hours before the operation. The intensity of pain (VAS score), sedation score, and nausea and vomiting were recorded postoperatively.

Results: In this study, 60 patients were enrolled in each group. The total VAS (Visual Analogue Scale) score was significantly lower among patients receiving Memantine and the satisfaction was significantly higher compared to the Dextromethorphan and placebo groups (P-value <0.001).

Conclusion: The present study results indicate that Memantine has a relatively better outcome compared to Dextromethorphan or placebo in reducing the post surgical pain among patients undergoing orthopedic surgeries. It also reduced the need for post surgical opioid use and improved the patients’ satisfaction. 


Comparison of adding neostigmine and fentanyl to bupivacaine in caudal analgesia in pediatric inguinal herniorrhaphy

Omid Aghadavoudi, Amir Shafa, Zahra Nowrozi

Journal of Cellular & Molecular Anesthesia, Vol. 2 No. 4 (2017), 11 December 2017 , Page 165-170


Objective: The aim of the present trial was to compare efficacy and adverse effects of neostigmine against fentanyl when used as adjuvant to bupivacaine in caudal anesthesia.

Method: A total of 140 children, aged 1-6 year scheduled to elective herniorrhaphy, were enrolled. Exclusion criteria were sacral area infection, history of allergic reactions to local anesthetics, bleeding tendency, neurological or spinal disease and lack of parent consent. Patients were assigned, using permuted block randomization method, into four groups of 35. Children in the first group received a caudal injection of 0.5 ml/kg bupivacaine 0.25% plus fentanyl 1µ/kg. The second group received 0.5 ml/kg bupivacaine 0.25% plus neostigmine 1µ/kg. Patients in the third group received 0.5 ml/kg bupivacaine 0.25% plus combination of fentanyl 1µ/kg and neostigmine 1µ/kg, and those in the fourth group only received 0.5 ml/kg bupivacaine 0.25% concentration. To assess pain intensity, Wong-Baker Scale was used. Time to first analgesic request and the dosage of analgesic agent was recorded. Data were analyzed using SPSS 17.0.


Significant differences were observed among groups in terms of number of patients needing analgesic (p=0.01), time to first analgesic request (p=0.005) and analgesic dose. (p=0.05) The lowest number of requests for analgesia, lowest dose of pethidine and longest time to first analgesic request were in patients receiving combination of bupivacaine, neostigmine and fentanyl.

Conclusion: The present study shows that the combination of fentanyl and neostigmine, could prolong duration of analgesia, and decrease severity of pain when added to bupivacaine

Comparing the Efficacy and Safety of Dexmedetomidine-Lidocaine and Propofol-Fentanyl-Midazolam Combinations during Endoscopic Retrograde Cholangiopancreatography

Mohammadreza Moshari, Bahman Malek, Maryam Vosoughian, Maryam Vosoghian, Mastaneh Dahi-Taleghani, Mahshid Ghasemi, Seyed Mohammad Seyed-Alshohadaei

Journal of Cellular & Molecular Anesthesia, Vol. 2 No. 4 (2017), 11 December 2017 , Page 171-179

Background and Aims: Propofol is commonly used for providing sedation in endoscopic retrograde cholangio-pancreatography (ERCP). It’s simple to use and effective but presents cardiovascular and respiratory adverse effects. Recently, dexmedetomidine has been tried but very little evidence exists to support its use. The aim of this study was to compare the efficacy and safety of combination of dexmedetomidine and lidocaine (DL) with the standard propofol-fentanyl (PF) regimen.

Methods: After approval of the hospital ethics committee, 63 patients (18-60 years of age) were randomly divided into 2 groups. Thirty-one patients received a PF combination (group PF), and 32 patients received DL combination (group DL). The level of sedation was adjusted to achieve a Ramasy Sedation Scale (RSS) score of 3 (moderate sedation) in both groups of patients. Arterial pressure (MAP), heart rate (HR), and peripheral oxygen saturation (SpO2) during ERCP and recovery was continuously assessed.

Results: The oxygen saturation (SpO2) showed high statistical significant differences between both groups throughout the procedure with stability in DL group (P<0.01). There was no statistical difference in HR and MAP between the two groups (P>0.05). Post-procedural recovery time was significantly shorter in PF group (15.97±3.27 min) compared with (19.38±5.64 min) DL group (p<0.01). PONV was 3.2% in PF group, while it was absent in DL group. No drug adverse effect or cardiovascular complications were observed in both groups.

Conclusion: Dexmedetomidine and lidocaine combination as total intravenous anesthesia (TIVA) during ERCP not only did not reported any oxygen desaturation (SpO2<90%) but also showed better stability of oxygen saturation (SpO2) and less PONV when compared with propofol and fentanyl combination.

The Effects of 6% Hydroxyethyl Starch Compared with Normal Saline on Controlling Undesirable Hemodynamic Changes Following Spinal Anesthesia in Patients Undergoing Orthopedic Surgery: A Randomized Clinical Trial

Siamak Yaghobi, Amir Hesam Alirezaei, Mahmood Bakhtiyari, Marzieh-Beigom Khezri, Niloufar Massoudi

Journal of Cellular & Molecular Anesthesia, Vol. 2 No. 4 (2017), 11 December 2017 , Page 180-188


Objective: The aim of the current study was to compare the effects of normal saline solution and 6% hydroxyethyl starch (HES/HAES) solution on hemodynamic changes after spinal anesthesia in patients undergoing lower limb orthopedic surgery.

Method: This randomized clinical trial was performed on 50 patients undergoing surgery, aged 20-60, with physical status of ASA I, II. Before surgery, the hemodynamic status of each patient including systolic and diastolic blood pressure, heart rate, and central venous pressure was measured. Then, the patients were randomly divided into two groups and for the control group, 7 ml/kg 9% (or normal) saline and for the experimental group 6% hydroxyethyl starch were administered. Hemodynamic indices were re-measured after the completion of infusion, and then spinal anesthesia was performed. After anesthesia, hemodynamic indices were measured every 5 minutes for 1 hour and then every 10 minutes for 2 hours. The analysis of variance (ANOVA) for repeated measures was used to evaluate the significant changes in hemodynamic indices.

Results: The mean and standard deviation of systolic and diastolic blood pressure, heart rate, and central venous pressure in the control group were 113.0 (7.3), 73.0 (6.0), 95.6 (5.7), and 5.8 (0.9), respectively, and in the intervention group were 104.8 (5.5), 66.1 (4.2), 95.8 (8.2), and 4.3 (0.9(. ANOVA for repeated measures showed that the incidence of decreasing changes in systolic and diastolic blood pressure, heart rate, and central venous pressure of the patients for whom hydroxyethyl starch was prescribed was significantly less than that of the patients for whom normal saline was prescribed.

Conclusion: Hydroxyethyl starch has a more effective role in controlling hemodynamic changes before spinal anesthesia than normal saline.


Acute post-operative pain and gut microbiota; is there any (clinical) relationship?

Elham Alipoor, Mahdi Shadnoush, Ali Dabbagh

Journal of Cellular & Molecular Anesthesia, Vol. 2 No. 4 (2017), 11 December 2017 , Page 189-193

Gut microbiota are the primary focus for a number of active research fields; one of their main areas of effect seem to be their effects on acute pain. Though it is generally realized that development of gut microbiota is after birth, the initial microbial core originates from maternal microbiota in fetus life, rapidly colonizing to adulthood microflora in 3-5 years. Understanding the crosstalk between microbiota, changes in gut flora and post-operative pain, and recognizing the underlying mechanisms are novel fields of study.