The miracle of Lidocaine: Second Look with Cellular and Molecular Perspectives

Mahnoosh Foroughi

Journal of Cellular & Molecular Anesthesia, Vol. 3 No. 1 (2018), 31 January 2018 , Page 1-2

The pain phenomena as a disabling state but normal fact in human have been noticed to alarm and concern to the tissue injury and damage. Pain management is one the most worldwide clinical challenges in general population that is associated with considerable health care expenses, decreased productive time and impression on the quality of life. Numerous studies have been done to identify its pathophysiology and effective therapeutic agents. Attention to pain etiology, the relationship of inflammatory pathways, the molecular mechanisms and involved transmitters have given insights to novel approaches with more effective pain relief agents. In addition to over the counter analgesic and prescription medicine (NSAIDs, opioids, COX-2 inhibitors), there is no consensus about the analgesic role of herbal medicines. Cochrane library reviewed the place of herbal medicine in low back pain. They showed although the RCTs were not large trials and well-designed but herbal medicine could reduce pain more than placebo in short term without significant side effects (1).Lidocaine as local/regional anesthetic agent has been introduced to reduce acute postoperative pain, the chronic pain conditions, myofascial pain, refractory neuropathic pain and neuralgia. In cancer pain patients with refractory to opioid agents, lidocaine infusion could achieve adequate analgesic state (2). Review of literature shows the recovery improvement by lidocaine infusion depends to the type of surgery. There is strong evidence to decrease pain scores in abdominal surgeries (both open and laparoscopy). In prostate, breast, thoracic and spine operations, the evidence is moderate with small benefit. In cardiac surgery, lidocaine infusion would decrease postoperative cognitive disorder with no analgesic effect (3). Lidocaine acts predominantly through blocking sodium channels. These channels in cell membrane would be upregulated and more excitable in neuropathic pain. Moreover lidocaine potentiates the ATP production and release of endogenous opioids. It has anti-inflammatory properties, reduces the level of circulating inflammatory cytokines and inhibits the stimulatory amino acids and thromboxane A2. The lidocaine metabolite attenuates nociceptive effect by increasing glycine level. Intravenous infusion of Lidocaine at the time of operation had been proved to be analgesic immediately after surgery until 24h later with recovery improvement. The low plasma level (0.5-5 μg/ml) is adequate for pain relief with reasonable safety profile. Different treatment regimens have been described: low vs, high dose (< or > 2mg/kg/h) and diversity in infusion time (until the end of surgery vs, prolonged infusion). Although it is short acting but prolonged anesthetic effect has been reported even after single treatment. Its analgesic effect may be constant for more than 6h and reduced pain level for several days. With consideration of short biologic half-life it couldn’t be interpreted. The analgesic effect is more pronounce in elderly patients than young and it is more efficient in more severe pain vs. lower intensity pain. The most frequent reported adverse effects during lidocaine infusion are: nausea, vomiting, lightheadedness, tinnitus, muscle spasm, perioral paresthesia and cardiac dysrhythmias. All of them would respond to dose reduction. It is inexpensive, comparable and as effective as epidural catheter without related neurologic complications. Although there is no consensus in dosing and infusion time, but is suggested to be part of treatment in opioid dependent persons (2-6). In this issue two pain related articles would be discussed:” Potential role of herbal medicine in alleviating pain and inflammation in osteoarthritis: A review”, and “Effect of intravenous infusion of Lidocaine on pain reduction after caesarean section under general anesthesia (7, 8) There are well defined strategies to control pain, reduce postoperative bleeding and homeostasis maintenance. Balancing the homeostasis, correction of acid base irregularity, pain management, bleeding

control and reduction of blood loss during surgery are part of the main skills of anesthesiologists. Today attention to cellular and molecular aspects of mentioned items are the more interesting topics. Consideration of molecular basis of these items are the main aim of the Journal of Cellular and Molecular Anesthesia.

Original Articles

Effect of Acid-Base Balance on Cytokines Serum Levels and Short-Term Outcomes in Kidney Transplant Recipients; a Randomized Clinical Trial

Mohammad Fathi, Nilofar Massoudi, Navid Noraee, Narges-Sadat Ghaemi, Dawar Amani, Ali Asadirad

Journal of Cellular & Molecular Anesthesia, Vol. 3 No. 1 (2018), 31 January 2018 , Page 3-13

Background: Control of blood acids and bases can help prevent many potentially life-threatening disorders in end stage renal disease (ESRD) patients. Aim of this study was to assess the effect of acid-base balance on cytokines serum levels and short-term outcomes in kidney transplant recipients.
Materials and Methods: In this randomized clinical trial study, 40 patients with end-stage renal disease aged 18 to 70 who had undergone a kidney transplant from a living donor in Modarres hospital during 2016-2017 were included. The primary outcomes measured in this study were sera levels of cytokine such as IL-2, IL-10, IFN-γ and BUN and Cr serum after the treatment of acidosis in kidney transplant recipients.
Results: Mean±SD of the patient’s age was 42±12.6 years. Results showed that there is a significant difference in means of IL-2, IL-10, and IFN-γ between the intervention and control groups over the time (for all p<0.05). We also found that correction of acidosis occurred with reduces of IFN-γ to -1.74 in the intervention group compared to the group receiving saline (P=0.011); and reduction for IL-2 was -1.37 (p=0.025). The concentration of anti-inflammatory cytokine of IL-10 was increased to 2.85 (P<0.001).
Conclusion: The results clearly suggest that correction of acidosis in renal transplant patients during surgery helps improve the performance of allograft in the short run; however, more studies are recommended, taking into account the long-term and short-term effects of this intervention.
Keywords: Cytokines, Kidney Transplantation, Acid-Base Balance, Randomized Controlled Trial

Bleeding Episodes Among Patients with Congenital Fibrinogen Disorders, a Study On 12 New Iranian Patients

Majid Naderi, Parvin Rahamani, Shaban Alizadeh, Hengam Razavi, Akbar Dorgalaleh

Journal of Cellular & Molecular Anesthesia, Vol. 3 No. 1 (2018), 31 January 2018 , Page 14-17

Background: Congenital fibrinogen disorders (CFDs) comprise about 10% of rare bleeding disorders (RBDs). CFDs are divided into two groups of quantitative (afibrinogenemia and hypofibrinogenemia) with autosomal recessive inheritance pattern, and qualitative (dysfibrinogenemia, hypodysfibrogenemia) disorders, mainly with autosomal dominant inheritance pattern. Sistan and Baluchestan Province in Iran, with its high rate of consanguineous marriages, has a high incidence of RBDs including CFD. In the current study, we report clinical manifestations of patients with CFDs.

Methods: Twelve new Iranian patients from Sistan and Baluchestan Province with different types of CFDs were selected for this study. Diagnosis of CFDs was based on clinical features and familial history followed by laboratory assessment by routine and specific coagulation tests including prothrombin time (PT) and activated partial time tests (APTT), as well as FI activity assay by Clauss method.

Results: Out of 12 patients, 3(25%) had afibrinogenemia, 7(58.3%) had hypofibrinogenemia while 2(16/7%) were suspected of having dysfibrinogenemia. Although umbilical cord bleeding (UCB) 9(75%) was the most common clinical presentation among the study population, this feature was not observed among patients with dysfibrinogenemia. Hematoma (100%) was the most common presentation of patients with dysfibrinogenemia. 

Conclusion: Results of this study revealed that some clinical presentations are the diagnostic features of CFDs and can be used for precise and in-time diagnosis CFDs in conjunction with family history and laboratory findings.

Keywords: Fibrinogen Deficiency; Congenital Afibrinogenemia; Blood Coagulation Disorder; Afibrinogenemia

Comparison of Two Methods of Bolus and Infusion of Tranexamic Acid in Reduction of Blood Loss in Total Knee Arthroplasty

Mohammadreza Moshari, Bahman Malek, Mohammadreza Minator-Sajjadi, Maryam Vosoghian, Mastaneh Dahi, Mahshid Ghasemi, Razieh Shekari

Journal of Cellular & Molecular Anesthesia, Vol. 3 No. 1 (2018), 31 January 2018 , Page 18-21


Background: So far, many studies have been performed to determine the optimal dose and regimen of tranexamic acid to reduce preoperative and postoperative blood loss in primary total knee arthroplasty. In the present study, two different methods of administration (bolus and infusion), were compared.

Materials and Methods: Forty patients were randomized in the two groups (A and B) of 20 patients each. All patients received 500 mg tranexamic acid before inflation of tourniquet. Group A (mean age, 64± 6.1 years) received 500 mg tranexamic acid 10 minutes before loosening of tourniquet and group B (mean age, 63.5 ± 7.7 years) received 500 mg tranexamic acid through IV infusion during 6 hours from the time of tourniquet loosening (total dose of TA, 1 g in both groups). Intraoperative blood loss,postoperative drainage (in 6 and 12 hours), blood transfusion (in 48 hours), and decrease in hematocrit and hemoglobin (6 and 12 hours later), were compared between the two groups.

Results: The patients in group B had lower intra- and postoperative blood loss in 6 and 12 hours and also had lower decrease in hemoglobin, and their packed cell transfusion rate was significantly lower compared to the group A.

Conclusion: The findings of this study indicated that infusion administration of tranexamic acid in primary total knee arthroplasty, was more effective in the reduction of perioperative blood loss as well as need for blood transfusion in 48 hours.

Effect of Intravenous Infusion of Lidocaine on Pain Reduction after Cesarean Section under General Anesthesia

Anahita Hirmanpour, Reihanak Talakoub, Hamed Mansouri

Journal of Cellular & Molecular Anesthesia, Vol. 3 No. 1 (2018), 31 January 2018 , Page 22-30

Background: The present study was conducted to evaluate the effect of Lidocaine on pain reduction during and ileus and the need for opioids after caesarean section.

Methods: For this randomized double-blind controlled clinical trial, 40 ASA I, II pregnant women who were candidates for caesarean section with general anesthesia, were randomly allocated into two groups of Lidocaine receivers and placebo using randomized block design; the Lidocaine group received 1.5 mg/kg of Lidocaine right before the surgery and then its infusion with a dose of 2 mg/kg.h until the end of the surgery and the placebo group received normal saline with the same volume and application. Patients’ pain intensity was measured using numerical rating scale (NRS), 0 (entering the recovery), 0.5, 1, 4, 12 and 24 hours after the surgery.

Results: Lidocaine decreased the systolic and diastolic pressures of the patients only during the first minute after intubation, decreased the mean of arterial blood pressure at the 10th minute after intubation and 40th minute after surgery, and also decreased the mean of patients’ pain intensity, Diclofenac and Pethidine consumption, side effects (nausea and vomiting) and reduced the time interval before the first time of tolerating oral liquids; but it had effect on infants’ Apgar score 1 and 5 minutes after delivery.

Conclusions: Lidocaine was definitely effective on reducing the intensity of pain, opioid and non-steroidal anti-inflammatory drugs consumption and ileus after surgery with the least occurrence of side effects for mothers and infants.

Brief Communications

Treacher Collins Syndrome; Anesthetic considerations and Molecular Findings

Shahram Sayyadi, Morteza Jabbari Moghadam, Alireza Mirkheshti, Elham Memary, Dariush Abtahi, Sohrab Salimi, Ardeshir Tajbakhsh

Journal of Cellular & Molecular Anesthesia, Vol. 3 No. 1 (2018), 31 January 2018 , Page 31-34

Treacher Collins Syndrome (TCS) is a rare disease with mandibulofacial dysostosis. The deformities accompanied by this syndrome could cause especial challenges for anesthesiologist. On the other hand Treacher protein is well recognized in the pathogenesis of this syndrome. In this report we want to present a successful management of a patient with Treacher Collins syndrome and also describe new advances in the molecular aspect of this disease.


Potential Role of Herbal Medicine in Alleviating Pain and Inflammation in Osteoarthritis: a Review

Mahdi Mahdavi, Mahdi Taherian, Hossein Maghsoudi, Reza Taherian

Journal of Cellular & Molecular Anesthesia, Vol. 3 No. 1 (2018), 31 January 2018 , Page 35-44

Osteoarthritis (OA) is a rheumatological disorder accompanied with imbalance between anabolic and catabolic mediators which leads to the destruction of homeostasis of articular cartilage. Currently, Steroids and non-steroidal anti-inflammatory drugs are commonly used in the management of OA. Besides the various side effects of these drugs, they can just alleviate symptoms of OA. Hence, to achieve safe and efficacious drugs, the research tendency toward exploration of novel sources has been grown up. Various previous researches have focused on the use of medicinal plants in the treatment of OA. This review focuses on the most efficacious medicinal plants and drugs considering related laboratory and clinical evidences. More investigations are needed to develop therapeutic agents with disease-modifying properties to treat OA.