In 1908, a German surgeon professor August Bier, introduced an anesthesia method which is nowadays called IVRA O’Bier’s block. IVRA is a simple, safe and economic technique for short lasting upper limb surgeries. The main problem of IVRA is that the required LA dose is very close to the toxic dose. Many attempts have been done to overcome this problem as giving a mixture of small doses of two local anesthetics or giving small dose of LA and potentiating its effect by alkalinization, addition of adjuvants as potassium, opioids, neostigmine, NSAIDs, alpha adrenergic agonist, ketamine or muscle relaxants. Unfortunately, those adjuvants beside their potentiating effects, they have some drawbacks as nausea, vomiting, cardiovascular and respiratory depression. Until now, there is no adjuvant without drawbacks, but we hope in the future to find the ideal adjuvant which has potentiating effect without drawbacks.The aim of this work is to compare the effect of adding each of fentanyl, tenoxicam, neostigmine, and pancuronium to the relatively small doses of lidocaine on the characters of the produced IVRA for upper limb orthopedic surgical procedures to find out the best improving adjuvant without or at least with minimal side effects.The upper limb is innervated by radial, median, ulnar nerves, musculocutaneous nerve, circumflex nerve, medial cutaneous nerve of the arm, and medial cutaneous nerve of the forearm, all arise from brachial plexus.The venous system of the upper limb divided into superficial and deep veins. The superficial veins are dorsal venous arch, cephalic vein, accessory cephalic vein, basilic vein, median cubital vein and median antebrachial vein. The deep veins are deep veins of hand, deep veins of forearm, brachial vein, and axillary vein. The superficial veins and the veins of the long bones of upper limb drain in the deep veins.Pharmacologically, lidocaine is amide type local anesthetic of moderate potency and duration but of good penetrating power and rapid onset and effective by all routes of administration. The main uses are for local anesthesia, postoperative pain relief, prevention and control of post-extubation laryngospasm, pharmacological sympathetic block, and control of ventricular arrhythmias.Fentanyl is extremely lipid soluble opioid which is 50 times more potent than morphine. It is used for premedication, neuroleptic analgesia and as adjuvant to general and regional anesthesia.Tenoxicam is non-steroidal anti-inflammatory agent with analgesic antipyretic properties. It is used for treatment of painful orthopedic and surgical condition and recently is used as adjuvant for IVRA.Neostigmine is a reversible anticholinesterase. It has nicotinic (increase muscle power)and muscarinic effects (side effects). It is used to reverse the effect of muscle relaxant at the end of general anesthesia, treatment of myasthenia gravis, and as adjuvant to regional anesthesia.Pancuronium is a non-depolarizing muscle relaxant. It has beside muscle relaxing effect, vagolytic and may be sympathomimetic effect. It is used to facilitate intubation and mechanical ventilation, abdominal muscle relaxation beside as adjuvant to IVRA.Indications of IVRA is divided into anesthetic for minor surgical procedures below elbow or knee and therapeutic for upper or lower limb sympathetic blockade.Contraindications of IVRA are uncooperative patient, severe Raynaud’s disease, sickle cell disease, severe hypertension, allergy to local anesthetic, myasthenia gravis, infection or crush injury to the limb and surgery which will take more than 60 minutes.Preoperatively, the patient should be visited for clinical assessment, preparation, explanation of the technique, taking a consent, giving instructions as at least 8 hours fasting from food and water and prescribing some medications.Equipments for establishment of IVRA include; small size IV cannula, plastic tube extension, plaser tape, syringes, saline, local anesthetic, adjuvant drugs, Esmarch bandage, conjoint cuff or two separate cuffs tourniquet, pressure source, manometer, and soft padding under the tourniquet.The technique of establishment of IVRA include 5 steps;Step I: It is the step of application of an IV cannula in the most peripheral vein in the operated limb.Step II: It is the step of application of either 2 separate pneumatic cuff tourniquet or the proximal tourniquet firstly on the proximal ⅓ of the arm or conjoint pneumatic cuff tourniquet on the most proximal part of the arm or thigh.Step III: It is the step of limb exsanguination either by elevation of the limb for 3 minutes or by Esmarch bandage and then inflation of the proximal cuff to 100 mmHg above the base level of systolic blood pressure.Step IV: It is the step of LA mixture injection.Step V: After the onset of the anesthetic effect, it is the stage of inflation of distal and deflation of proximal tourniquet or application of distal tourniquet on the middle third of the arm (if not applied from the start) and inflation of it and deflation of the proximal one or inflation of the distal cuff and deflation of the proximal one.Postoperatively, the pneumatic tourniquet should be deflated by techniques of intermittent deflation and reinflation technique to avoid post-reperfusion shock.The commonly used LA for IVRA include lidocaine, prilocaine, bupivacaine, robivacaine, mepivacaine, 2-chloroprocaine, and articaine.The most commonly used adjuvants for IVRA are; opioids, tramadol, muscle relaxants, NSAIDs, alpha2-adrenergic agonists, sodium bicarbonate, ketamine, potassium, and neostigmine.The kinetics of the injected LA solution in venous system and nerve tissues are first filling the venous system, then diffuse outside it to reach around the peripheral nerve endings, small nerves and large nerve trunks. After that, it diffuses to the inside of the nerve tissues with subsequent block to their functions.Measures to increase safety during IVRA include that IVRA establishment should be in the theatre, good monitoring of patient hemodynamics, respiratory and central nervous system for early detection of earl signs of LA toxicity, equipments and drugs for resuscitation should be available, proper insertion and fixation of IV cannula, good exsanguination of the limb, soft padding under tourniquet to avoid skin injury, double cuff application technique to rapidly inflate one if the other is accidentally deflated, slow LA injection in distal limb vein, usage of the most safe LA, vasoconstrictors must never be used, proper tourniquet pressure, minimum tourniquet time is not less than 20 minutes, postoperative tourniquet deflation is by intermittent deflation nand reinflation method to avoid post-reperfusion shock.Measurements to increase effectiveness and success rate of IVRA are proper selection of the cooperative patient, good premedication, good exsanguination of the limb, double cuff technique, proper tourniquet time, proper choice of LA and adjuvant, and supplemental medications during IVRA.Advantages of IVRA include that it is simple, reliable, and economic technique, can be performed safely in patients with full stomach, respiratory and cardiovascular problems, and rapid offset of its anesthetic effect after cuff release allowing the patient to return home as soon as possible.Disadvantages of IVRA include pain and discomfort due to tight tourniquet application, lack of postoperative analgesic effect, probability of oozing from the surgical field, limited time, and LA toxicity which may be fatal.Complications of IVRA are LA toxicity, allergy, complications of the added adjuvants, complications of tourniquet (as skin bruises, blood oozing, etc…), failure of anesthetic effect, ischemia-reperfusion shock, compartmental syndrome and infection.This study was carried out on 150 patients of both sex undergoing minor surgical operations on the upper limbs at Zagazig University Hospitals. The patients were randomly divided into 5 equal groups:• Group I (control group); Their patients received 3 mg/kg of 0.5% lidocaine plus 5 ml of normal saline (as placebo).• Group II (fentanyl added group); their patients received 3 mg/kg of 0.5% lidocaine plus 25 microgram fentanyl diluted with normal saline up to 5 ml.• Group III (tenoxicam added group); their patients received 3 mg/kg of 0.5% lidocaine plus 20 mg of tenoxicam diluted with normal saline up to 5 ml.• Group IV (neostigmine added group); their patients received 3 mg/kg of 0.5% lidocaine plus 0.5 mg of neostigmine diluted with normal saline up to 5 ml.• Group V (pancuronium added group); their patients received 3 mg/kg of 0.5% lidocaine plus 0.5 mg pancuronium diluted with normal saline up to 5 ml.The technique of establishment of IVRA included 5 steps:1- Insertion of IV cannula in the vein of the dorsum of the hand.2- Application of the proximal pneumatic cuff on a well padded skin.3- Upper limb exsanguination by an Esmarch bandage that immediately followed by inflation of the preapplied proximal tourniquet to 100 mmHg more than the base level systolic blood pressure.4- Lidocaine adjuvant mixture was injected.5- Lastly, application and inflation of the distal pneumatic tourniquet on a well padded skin and deflation of the proximal one when the sensation was lost in the skin of the middle third of the arm.After injection of the local anesthetic mixture, the characters of the produced regional anesthesia were assessed as the following:I. Onset of the anesthetic effect which included:a- Onset of sensory block.b- Onset of motor block.II. Quality of the anesthetic effect by assessing the following:a- The degree of intraoperative patient discomfort.b- The amount of supplemental systemic analgesia that needed during the operation.c- Duration of tolerance to tourniquet pain.III. Recovery from the anesthetic effect of IVRA after tourniquet deflation which include:a- Time to return sensation.b- Time to return of motor power.IV. Duration of effective postoperative analgesic effect of IVRA.V. Postoperative analgesic consumption in the subsequent 24 hours of the operation.VI. The associated side effects which include:a- Lidocaine toxicity: In case of occurrence of some manifestations that indicate lidocaine toxicity, blood sample was taken from the patient to estimate the serum lidocaine toxic level (7 μg/ml) to confirm the diagnosis.b- Nausea and vomiting.c- Hemodynamic changes (HR and MABP).d- Respiratory changes (signs of respiratory depression).At the end of the operation, the tourniquet was released intermittently to avoid ischemia reperfusion shock.from this study, the characters of the resulting anesthesia in the various groups were as the following:- A significant decrease in the mean time of onset of sensory block in GN in comparison with the other groups. Also, a significant decrease in the mean time of onset of motor block in GN and GP in comparison to other groups with the superiority of pancuronium over neostigmine in decreasing this time.- A significant decrease in the patient discomfort during the operation and the amount of intraoperative supplemented analgesia in GF and GN in comparison to other groups with the superiority of GN over GF beside a significant increase in the duration of tolerance to tourniquet pain in GT and GN in comparison to other groups with no significant difference in comparison of GT with GN.- A significant delay in the mean time of return of sensory function in GN in comparison to the other groups beside a significant delay in the mean time of return of motor function in GN and GP in comparison to other groups with more delay in GP compared with GN.- A significant increase in the duration of effective postoperative analgesia in GF, GT and GN in comparison to GC and GP with superiority of GF over GT and GN and superiority of GT over GN.- A significant decrease in the amount of the required analgesia in the subsequent 24 hours of the operation in GF, GT, and GN in comparison to GC and GP with less amount of analgesia in GF compared with GT and GN and in GT compared to GN.The associated side effects were as the following:a- Lidocaine toxicity was not detected in any patient of all groups.b- Nausea and vomiting occurred in 2 patients of GF (6.6%) and 3 patients of GN (10%). Statistically, these 2 incidences differ significantly from the corresponding incidences of the other groups (0%) but both were statistically similar.c- Hemodynamic depression occurred in 6 patients (20%) in GN only. Statistically, this incidence showed significant difference when compared with the corresponding incidence of the other group (0%).d- Respiratory depression did not occur in any patient of the 5 groups.In conclusion, tenoxicam (20 mg) is the best adjuvant because it improved the characters of the resulting regional anesthesia without associated side effects. So, we recommend its usage. Other adjuvants were either improving the characters of the resulting IVRA but had side effects as neostigmine (0.5 mg) and fentanyl (25 micrograms) or nearly did not improve the characters of IVRA but had no side effects as pancuronium (0.5 mg). So, we did not recommend its routine usage by these used doses. Perhaps in future, investigators reveal that uses of smaller doses than that used in this study have improving effect on the IVRA characters without producing side effects.