Vitamin B12 infusion as an adjuvant to postoperative analgesia in patients undergoing lowerabdominal surgeries

4.

BRIEF RESUME OF THE INTENDED WORK:

4.1 INTRODUCTION AND NEED FOR STUDY

Postoperative pain due to tissue injury and surgical trauma is associated with neuroendocrine stress responses, catecholamine and inflammatory mediator release, and the central sensitization, which is considered to be one of the mechanisms responsible for the persistence of postoperative pain 1.  The noxious stimuli may cause the expression of the new genes in the dorsal horn of the spinal cord within 1 hour after tissue injury due to surgical trauma [2,3] Hence, the traditional separation between the acute and chronic pain is unproven because the acute pain may quickly turn into chronic pain. Also, the intensity of acute postoperative pain is a significant predictor of chronic postoperative pain [3,4] Preventing central sensitization with multimodal analgesic interventions could reduce the intensity or even eliminate acute postoperative pain and chronic pain after surgery. Furthermore, pain control after surgery improves the general condition of the patient and helps in early ambulation 5.

Opioids are frequently used to treat pain today, although they frequently produce ineffective analgesia and may cause dangerous side effects 5. Additionally, it has been noted that a single opioid dose may result in a persistent elevation in threshold pain sensitivity, which causes delayed hyperalgesia [5,6]. It is therefore vital to look for a new medication that would lessen postoperative pain and have fewer adverse effects.

Improvement of nonspecific low back pain was observed by intramuscular supplementation of vitamin B12.7 Moreover, neurogenic claudication distance was improved significantly after the application of vitamin B12 8. Treatment with vitamin B12 significantly improved spontaneous pain, allodynia, and paresthesia of patients suffering from neck pain. The analgesic effect was more obvious when treated with vitamin B12 9.

Possible B12 analgesic and anti-neuralgic mechanisms have been explained in various studies : interaction with mediators causing pain in nociceptors, increasing availability and effectiveness of norepinephrine and 5-hydroxitriptamine in pain inhibitory descending pathway; regeneration of damaged nerve fibers; stabilization of electric nervous excitability inhibiting ectopic discharges; and improved axonal transport, increasing nervous conduction velocity10,11,12  However,  single doses of  cyanocobalamin (5000mcg) is effective as analgesics in nociceptive pain. 13

This study is being carried out to find out the analgesic effect of vitamin B12 infusion in patients undergoing lower abdominal surgeries under subarachnoid block.

4.2 REVIEW OF LITERATURE:

1.     Abbas Ostad Alipour et al (2015)14 conducted a prospective randomized double blind study to compare the analgesic effects of intravenous injections of B vitamins alone and Diclofenac plus B vitamin during general anaesthesia and in PACU. Three groups of patients (n=35 each) undergoing orthopaedic surgeries were taken. The first group received 250 ml normal saline intravenous infusion. The second group received vitamin B(B1-20 mg, B6 -300mg, B12- 1000mg) intravenous infusion, The third group received 75 mg Diclofenac plus B vitamin in 250 ml  normal saline over 25 mts before induction of anaesthesia. Pre-induction and post induction haemodynamic parameters, analgesic effect and opioid requirements were measured. They concluded that Opioid requirement was significantly lower in the second and third group, and heart rate & systolic BP were increased in first group when compared to other 2 groups.

2.     Marzieh Beigon Khezri et al (2017)15 studied on preemptive analgesic efficacy by addition of vitamin B complex to Gabapentin versus Gabapentin alone in women undergoing caesarean section under spinal anaesthesia. 180 women were randomized to receive orally 300 mg Gabapentin or 300 mg Gabapentin plus 2 tablets of vitamin B complex 30minutes before surgery. The primary outcomes of this randomized, double-blind, placebo-controlled clinical trial were to evaluate the time for the first requirement of analgesic  and  the  total  analgesic  consumption in the  first  12 postoperative hours. In this study, postoperative analgesia was defined as the time from intrathecal injection of anesthetic solution to the first requirement of analgesic supplement. The pain intensity was evaluated in the recovery room, soon after shifting from the operating room and then at 2,4,8, and 12 hours after surgery with the use of visual analog scale (VAS) of pain from zero to  10 (0 no pain, 10 maximum imaginable pain). If the VAS score was more than 4 or the patient requested analgesia, diclofenac Na suppository 100 mg was given for postoperative pain relief. If the time interval between administration of diclofenac Na to patients request was less than 8 hours, intravenous pethidine 25 mg was given for breakthrough pain (VAS>4) relief.

The secondary outcome of this study was assessment of sedation level and the incidence of vomiting. The sedation level of patients after surgery were measured according to modified Ramsay score scale. The difference of the mean time to the first analgesic request in group GB  (5.06±3.19  hours)  versus  group  G  (4.48±2.24  hours)  was insignificant (95% Cl: 4.14-5.48; P=.377).The pain intensity in group GB was less than group G up to 12 hours after surgery (P<.001). Meanwhile,the totalanalgesic consumption in this group was less than gabapentin alone (P=0.034). The incidence of vomiting was similar in both the groups  (P=.206).The difference in Ramsay sedation scores in patients between the two groups were insignificant (P=.82). No adverse events were reported in this study. They concluded that total analgesic requirement within first 12 hours postoperatively  in patients who received gabapentin and vitamin B complex was less than patients receiving gabapentin alone.

3.      Scott Buessing et al (2019)16 study compiled the potential mechanisms of Vitamin B12 for the treatment of pain conditions. They concluded that Vitamin B12 causes regeneration of nerves, inhibition of Cyclo oxygenase enzymes and other pain signaling pathways, synergestic benefits of vitamin B12 when combined with other pain medications, including NSAIDS and Opiates.  Many clinical trials provided evidence for the effectiveness of vitamin B12  for  the treatment of  low back pain and neuralgia. They concluded that Vitamin B12 may prove to be an adjunctive for pain conditions.

4.     A study by G. Devathasan et al (1986) 17 assessed the analgesic effect of methyl cobalamin in chronic diabetic neuropathy.   They gave methyl cobalamin 1500mcg daily   for   3months  to  42 patients  with longstanding  diabetes with  symptomatic  neuropathy. They assessed deep tendon reflexes, sensory loss to pin prick, 2-point discrimination and electrophysiological investigations. They concluded that methyl cobalamin provides satisfactory symptomatic relief, and improvement in motor and sensory function is possible by promoting myelin and axonal phospholipid synthesis.

5.     Ismael Abdel-Latif    Shabayek (2019) et al 18 studied  on  comparison  of Preemptive Analgesic Efficacy of Addition of Vitamin B Complex to Gabapentin ( group GB) versus Gabapentin (group G) alone in 80 patients undergoing elective Orthopedic Surgery under Spinal Anesthesia. In their study patients were randomized to receive orally 300mg gabapentin or 300mg of gabapentin plus 2 Vitamin B complex tablets 30 minutes before surgery. In this study, postoperative analgesia was defined as the time from the intrathecal injection of anesthetic solution to the first requirement of analgesic supplement. The pain intensity of patients was evaluated at the end of anesthesia in the recovery room, then at 2, 4, 8, and 12hours after surgery using visual analog scale (VAS). Postoperative pain intensity and total analgesic consumption during 12 hours after surgery, vomiting  and  drowsiness  during recovery were assessed.  If the VAS exceeded 4 and the patient requested a supplement analgesic, diclofenac Na 75mg was given. They concluded that combination of vitamin B complex to Gabapentin reduced intensity of postoperative pain and the total amount of analgesic consumption within the first 12 postoperative hours following orthopaedic surgery under spinal anaesthesia.

5

  4.3 AIMS AND OBJECTIVES OF THE STUDY:

 To detect the analgesic effect of Vitamin B12 infusion in patients undergoing lower abdominal surgeries under subarachnoid block by analyzing:

1.     The duration of analgesia.

  MATERIALS AND METHODS:

  5.1 SOURCE OF DATA:

The present study will be conducted in patients between 18 to 60 years of age (ASA 1&2), undergoing lower abdominal surgeries under subarachnoid block in ESIC Medical College-PGIMSR, Rajaji nagar,  Bengaluru- 10 , from ……….2023 to …………..2024.

  5.2 METHOD OF COLLECTION OF DATA:

  Study design: Randomized comparative study.

   A. Study period: The study will be done between ……2023 to ……… 2024.

  B. Sample size:

 Khezri et al 15 conducted a study where patients received orally 300mg gabapentin (group G) or 300mg of gabapentin plus 2 vitamin B complex (group GB) tablets 30minutes before surgery and found that the duration of pain intensity improved with group GB. We hypothesize that adding Vitamin B12 infusion would prolong the duration of analgesia.

Keeping the power of the study as 95%, with significance  at the 5% level, the sample size was calculated using the formula n = f(α/2, β) × 2 × σ2 / (μ1 �’ μ2)2; where μ1 and μ2 are the mean outcome in the study groups respectively, σ is the standard deviation; we decided to enroll 36 patients in each group.

D. Inclusion Criteria:§  Patients who are willing to give informed consent. (ANNEXURE 1)

§  ASA grade 1 & 2. (ANNEXURE 2)

§  Patients aged between 18 to 60 years.

§  Patients undergoing lower abdominal surgeries.

  E. Exclusion Criteria:§  Contraindications to spinal anaesthesia.

§  Neurological disorder.

§  Coagulation disorder.

§  Hypotension.

§  Emotional instability.

§  Unwillingness.

§  Any anticipated difficulty in regional anaesthesia.

§  ASA grade III and IV.

§  Signs and symptoms of vitamin B12 deficiency Patients with history of coagulopathy.

§  Patients with history of allergic to local anaesthetics.

   G. Methodology: Following ethics committee approval, informed consent will be obtained from the patients. Detailed pre-anaesthetic evaluation will be done. Patients fulfilling the required criteria, scheduled for lower abdominal surgeries will be enrolled by random allocation into two groups (group A & group B) of  36 patients each using sealed envelope technique. The patients will be kept nil per orally for 8 hours prior to surgery. A proforma will be used to enter the data which includes patient’s particulars, indication for surgery, the anaesthetic details, intra-operative & post-operative monitoring etc (ANNEXURE- 3). All patients will be pre-medicated with tablet alprazolam 0.5mg & tablet Ranitidine 150mg on the night before surgery. Patients will be educated regarding the use of visual analog scale during pre -anaesthetic evaluation (ANNEXURE 4).

                                                 On arrival into the operating room, an 18G intravenous cannula will be inserted and  preloading   will be done with Ringer lactate solution 10 ml/kg/body weight over period of 15 to 20   minutes.  Patients are connected to standard ASA monitors.

In group A,  1000 mcg injection Vitamin B12 in 100 ml Normal saline will be given followed by  25 G Quincke spinal needle will be inserted at L3-L4 site. 2.5 ml of 0.5% hyperbaric Bupivacaine will be injected through spinal needle.

In group B, 100 ml Normal saline will be given followed by   25 G Quincke  spinal needle will be introduced at L3-L4 site and 0.5% spinal Bupivacaine (H) 2.5 ml will be given for spinal block.

 The following observations are made:

1. Haemodynamic parameters such as Pulse rate and blood pressure will be monitored at 5-minute intervals.

2.Duration of analgesia –time from the intra thecal injection of anaesthetic solution to time needed for first dose of post-operative rescue analgesic ( VAS ≥ 4).

3.Postoperatively both groups’ patients will be observed for the following up to 24hours.

1)   The duration of analgesia - It is defined as the time duration from the intra thecal injection of anaesthetic solution to time needed for first dose of  post-operative  rescue analgesia is given.

2)   Total amount of rescue analgesia given

3)   VAS scores

4)   Haemodynamic changes

5)   Side effects (nausea, vomiting, hematoma, LA toxicity)

Parenteral Injection Paracetamol 15 mg/Kg  will be given when VAS ≥ 4 (rescue analgesia).

Post operatively, pain will be assessed using VAS scale, with zero representing no pain and ten representing worst pain. Haemo-dynamic parameters and VAS for pain will be recorded at 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours.

H. METHOD OF DATA ANALYSIS:

                                             All characteristics will be summarized descriptively. For continuous variables, the              summary statistics of N, mean, standard deviation (SD) will be used. For categorical data, the number and percentage will be used in the data summaries and data will be analyzed by Chi square test for association, comparison of means using t test, ANOVA, and diagrammatic presentation. Other suitable methods of analysis will also be used as per need. If the p-value is < 0.05, then the results will be statistically significant otherwise it will be considered as not statistically significant. Data will be analyzed using SPSS software v.23.0. and Microsoft office 2007.