“COMPARISON OF THE EFFECTS OF TWO DIFFERENT DOSES OF PRE-EMPTIVE INTRAVENOUS TRAMADOL IN PREVENTING PERIOPERATIVE SHIVERING IN PATIENTS UNDERGOING SPINAL ANAESTHESIA FOR UROLOGICAL SURGERIES – A PROSPECTIVE STUDY IN WEST BENGAL”

Objective of proposed research :

General Objecttive:

This study is aim to assess and compare the efficacy two different doses of Intravenous Tramadol used pre-emptive manner to prevent perioperative shivering under spinal anaesthesia in patient undergoing urological surgery and to find out the suitable dose with lesser side effects. This study also aims to check any advantage of pre-emptive use of the Tramadol over the current practice of rescue tramadol in similar circumstances.

Specific:

(i)   To compare the efficacy of two doses of pre-emptive intravanous Tramadol in preventing postanaesthetic shivering in patients undergoing urological surgeries under spinal anaesthesia.

(ii)  To corelate any dose related adverse effects of pre-emptive administration of intravanous Tramadol.

(iii)To find out any advantage of preemptive use over the current practice of rescue tramadol in preventing perioperative shivering in study groups.

Methodology :    

After obtaining approval from the Institutional Ethics Committee, this prospective study will be carried out in following manner,

The study included 155 Urological surgery cases under spinal anaesthesia in three groups

Inclusion Criteria:

(i)   ASA grade I or II

(ii)  Patients of 18 -70 years age group

(iii)Either sex

Following patients will be excluded from the study,

(i)   ASA grade III & IV

(ii)  Patients requiring administration of blood or blood products during surgery.

(iii)  All patients with contraindications for spinal anaesthesia like patient refusal; infection at the site of injection; severe, uncorrected hypovolemia; true allergy to any of the drugs; and increased intracranial pressure, except in cases of pseudo–tumor cerebri (idiopathic intracranial hypertension).

(iv)  Known hypersensitivity to tramadol and other allergies.

(v)  Known history of alcohol or substance abuse,

(vi) Patient with fever & urinary tract infection (UTI).

Sample Size:

The sample size will be calculated using the following formula:

(Z α + Z β ) 2 { p 1 x (1- p 1 ) + q 1 x (1 – q 1 )

n = …………………………………………………………………..

d 2

Where,

n = Sample size

Z α = 1.96 at 95% Confidence Interval

Z β = Power of the study = 0.84

p 1 = Prevalence of shivering among patients undergoing spinal anaesthesia = 0.6 (Reference)

q 1 = Expected reduced prevalence of shivering among patients undergoing spinal anaesthesia = 0.3

d = Difference between p 1 and q 1 = 0.3

Therefore ,

(1.96 + 0.84) 2 { 0.6 x 0.4 + 0.3 x 0.7)

n  = 39.2

Adding 10% extra for non-response, the sample size will be (39.2+3.92) = 43.12 ~ 43.

Considering and adding 0.25 as sampling error factor i. e. 0.25 × 43= 10.75

So the final sample size in each group will be (43+10.75)= 53.75 ~ 54.

The patients were randomly allocated, using a draw of lots technique, to one of the two groups of 55 patients each.

Study groups

i)            Group-A: No Pre- emptive, only rescue Tramadol-1mg/kg.

ii)          Group-B: Pre- emptive Tramadol-0.5mg/kg. with rescue Tramadol-1mg/kg.

iii)          Group-C: Pre-emptive Tramadol 1mg/kg. with  rescue Tramadol-1 mg/kg.

Before onset of spinal anaesthesia, standard monitoring procedures will be established. Pulse rate, non-invasive blood pressure (NIBP), oxygen saturation (SPO₂), body temperature (core) will be recorded before the commencement of subarachnoid block (SAB) and thereafter at every 5 minutes, during intraoperative period; and every 15 minutes, for the rest of the observation period (4 hrous) will be recorded.

Subarachnoid block will be given with inj. Bupivacaine 0.5% (10-15 mg) at L_3-4 or L_4-5 interspace using 25 gauge Quincke’s needle, and blockage up to T_9-10 dermatome will be expected to be achieved.

The Study dose of Intravenous Tramadol will be administered 05 minutes prior to the administration of Spinal Anaesthesia (Sub Arachnoid Block).

All operation theatres will maintain constant humidity (70%) and an ambient temperature of around 21°C to 23°C. Oxygen will be administered to patients of SPo2 < 93% .No active warming of the patient will be done. No means of active re-warming will be used. Intravenous fluids and anaesthetic drugs will be administered at room temperature. Preloading will be not done in any of the groups as we did not want intravenous fluid to influence the onset of shivering.

Ondansetron, Granisetrone, Dexamethasone, Dexmedetomidine, Pethidine, Ketamine, Clonidine, Meperidine, Remifentanil, Buprenorphine , Nefopam, Benzdiazepam & any other drug which may interfare with shivering in post spinal anaesthesia, are desired to be avoided if not essential to the case, to exclude bias.

Grading of shivering was done according to the criteria by Wrench which

Patients who develops either grade 2, grade 3 or grade 4 of shivering will be recorded in the study. The attending anaesthetist will record the time in minutes at which shivering started. The onset and duration of shivering will be recorded. Duration of surgery and spinal anaesthesia (onset of shivering), severity of the shivering, time to disappearance of shivering (in minutes) and response rate (shivering ceased after rescue dose in 15 minutes). Duration of surgery will be noted, and duration of spinal anaesthesia will be recorded by assessing spontaneous recovery of sensory block using pin-prick method and observing spontaneous movements of limbs in the postoperative period.

Modified Bromage score as used by Breen et al, will be used to assess the onset and recovery of SAB.

Recurrence of shivering will be observed for 4 hours post operatively.It will be treated with additional dose of tramadol (1 mg/kg IV) in the respective groups. Side effects like nausea, vomiting, bradycardia (<50/min), hypotension (>20% of baseline), dizziness. Sedation score will be assessed with a four-point scale [Filos]

• Awake and alert
• Drowsy, responsive to verbal stimuli
• Drowsy, arousable to physical stimuli
• Unarousable

Bradycardia, hypotension and vomiting will be treated with atropine, mephenteramine and metaclopramide, respectively, in titrated doses when required.

Ondansetron, Granisetrone, Dexamethasone, Dexmedetomidine, Pethidine, Ketamine, Clonidine, Meperidine, Remifentanil, Buprenorphine , Nefopam, Benzdiazepam & any other drug which may interfare with shivering in post spinal anaesthesia, are desired to be avoided if not essential to the case, to exclude bias.

Statistical analysis will be done using suitable statistical formulae according to the SPSS package .A P value <.05 was considered statistically significant.

Expected outcome :  

In the present study, we compared the efficacy of two doses of intravenous tramadol for prevention of shivering after spinal anaesthesia in patients undergoing various urological surgeries. Tramadol is an opioid analgesic with opioid action preferably mediated via μ (mu) receptor with minimal effect on kappa and delta binding sites. Tramadol also activates the monoaminergic receptors of the descending neuraxial inhibiting pain pathway. The anti-shivering action of tramadol is probably mediated via its opioid or serotonergic and noradrenergic activity or both.

In the present study, we expect to establish the relation of efficacy of prevention of shivering with the enhancement of doses of Intravenous Tramadol in post–spinal anaesthesia shivering, when given prior to the Sub Arachnoid Block. We expect more adverse effect of drug with higher dose of tramadol. Slowed breathing/long pauses between breaths, or shortness of breath, Bradycardia, Hypotention, nausea and dizziness will be recorded will be compared between two doses of Intravenous Tramadol. We expect to establish a hypothesis on efficacy and weightage to the severe side effects.