Magnesium Sulfate versus Fentanyl for attenuation of pneumoperitoneum induced hemodynamic changes in laparoscopic cholecystectomy - A prospective randomized controlled study

Laparoscopic cholecystectomy was first performed by Philipe Mouret in 1987. Since then, this procedure has become prevalent worldwide because of its benefits compared to open cholecystectomy. For laparoscopic cholecystectomy, carbon dioxide is commonly used to create pneumoperitoneum. Pneumoperitoneum and Carbon dioxide can induce stimulation of neuroendocrinal pathway causing increase in level of catecholamines, renin, vasopressin, prostaglandin and cortisol, which is seen in form of abrupt elevation of arterial BP, systemic vascular resistance and decreased cardiac output.

Methods to reduce hemodynamic changes following pneumoperitoneum induced effects include administration of some pharmacological preparations to the patients such as α2 agonist, β blocker, vasodilators, opioids ,MgSO4 etc. which will help us to modify the pneumoperitoneum induced stress response and improving the patients postoperative outcome.

Fentanyl citrate being narcotic analgesic interacts predominantly with the μ opioid receptor and exerts its principal pharmacological effect on CNS. Its primary action of therapeutic value is analgesia and sedation. It also leads to obtundation of pressor response of laryngoscopy /intubation and pneumoperitoneum and thereby it attenuates increase in arterial pressure and HR.

Magnesium sulfate is an antagonist of NMDA receptors that has shown to have a potential to reduce intra-operative anesthetic requirements and to reduce post-operative pain. It has shown to inhibit the release of catecholamines from adrenergic nerves and produces vasodilatation, attenuates vasopressin-mediated vasoconstriction and normalize sensitivity to vasopressin. Intravenously administered magnesium sulphate is capable of attenuating the adverse hemodynamic responses associated with endotracheal intubation also.

So, here we will compare Fentanyl with Magnesium sulfate for attenuation of pneumoperitoneum induced hemodynamic response in patients undergoing laparoscopic cholecystectomy.

STUDY HYPOTHESIS :

Our Study may find both adjuvants effective but MgSO4 may be a better adjuvant than fentanyl in terms of attenuation of pneumoperitoneum induced hemodynamic response and postoperative analgesia in patients undergoing laparoscopic cholecystectomy.

AIMS AND OBJECTIVES :

Aims-Magnesium sulfate versus Fentanyl for attenuation of pneumoperitoneum induced hemodynamic changes in laparoscopic cholecystectomy.

Objectives :

Primary objective:-

To compare Hemodynamic parameters like HR, SBP, DBP, MAP

Secondary objectives:-

To assess postoperative analgesia

To observe complications if any.

STUDY DESIGN:

Study Site: Major Operation theatre, B.J. Medical College, Civil Hospital, Ahmedabad

Study Type: Prospective Randomized controlled study

Sample Size: Sample size is calculated using MedCalc software from the Pilot study result. Taking HR following intubation, the difference of mean was 12.4 and standard deviation of 8.98 and 11.22 with type 1 error at α 0.05 and type 2 error at β 0.2. Minimum sample size per group came to 11. We will study 25 patients in each group considering drop outs and attrition loss.

PATIENT SELECTION :

INCLUSION CRITERIA:

Patients in the age group20 to 60 year

Either gender

ASA PS I and II patients

Patient undergoing elective laparoscopic surgeries.

EXCLUSION CRITERIA:

Patient refusal to participate in study

Patient having cardiovascular, respiratory, hepatic, renal, neurologic, psychiatric or metabolic disease.

ASAPS III and IV patients

Pregnant woman

Morbid obesity

Those with a history of alcohol.

Patients on antihypertensive, antipsychotics , analgesics corticosteroids or sedative medications.

Had a history of hypersensitivity to any of the study drug.

MATERIAL AND METHODOLOGY :

Study drugs are Fentanyl and Magnesium sulfate which are available in Government supply. If not available then I will purchase on my own.

Source of data:

Present study will be conducted on 50 patients aged 20-60 years who are scheduled for laparoscopic cholecystectomy surgery in civil hospital, Ahmedabad, Gujarat.

Method of collection of data:

Randomization was done by computer generated number. Allocation concealment was done using opaque envelopes to randomize patients into 2 groups.

1. Group F: Patients who will be given Fentanyl 2mcg/kg diluted in 100ml NS intravenously over 10 minutes, 10 minutes prior to induction.

2. Group M: Patients who will be given MgSO4 (40 mg/kg)diluted in 100ml NS intravenously over 10 minutes, 10 minutes prior to induction.

Method:

Pre -operative evaluation will be carried out a day before surgery. A thorough history will be taken and detailed examination will be carried out. Patient will be explained about VAS (visual analogue scale).

Patient will be subjected to routine and relevant investigations like hemoglobin, renal function tests, serum electrolytes, random blood sugar, coagulation profile, chest X-ray PA view and ECG and other special tests needed according to procedure.

All the patients will be kept nil by mouth as per ASA guidelines.

Tablet ranitidine 150 mg and tablet lorazepam 2mg will be given in night before day of surgery.

On the day of surgery informed, written consent will be taken and prior to operation after explaining about the procedure to be done, participation in the study and doubts will be cleared.

Patient will be taken on O.T table and standard monitors including non-invasive blood pressure (NIBP), pulse oximetry (SpO2), electrocardiogram (ECG), will be attached.

After establishing intravenous access using an 18G cannula, Injection ringer lactate will be started and baseline vital parameters will be recorded.

All patients will be given either of study drugs 10 minutes prior to induction over 10 minutes.

All patients will be pre medicated with Injection glycopyrolate 0.004mg/kg, Injection Ondansetron 0.15mg/kg, Injection Paracetamol 1 gm IV and injection xylocard 1.5 mg/kg intravenously.

Patient will be pre oxygenated using Bain’s circuit with100%O2for five minutes. Induction will be done with Injection Propofol2-3 mg/kg intravenously till the loss of eyelid reflex and Injection succinylcholine2mg/kg IV. Tracheal intubation will be done with appropriate sized of cuffed endotracheal tube (for female ETT of 7,7.5 and for males ETT of 8;8.5). Following confirmation of bilateral equal air entry, ETT will be connected to EtCO2 and closed circle circuit will be used for IPPV.

Maintenance of anesthesia will be done using O2:air(50:50), Sevoflurane 2-2.5% and Injection Vecuronium bromide 0.1 mg/kg as a loading dose and 0.02 mg/kg maintenance dose.

Any hemodynamic changes (deviation of 20% from baseline) will be managed accordingly. For hypotension NS 250-300 ml will be given first if not resolved with this then injection mephentramine 6mg IV will be given. For hypertension nitroglycerine infusion will be used.

Ventilation will be adjusted to maintain EtCO2 in range of 35-40 mmHg.

CO2 pneumoperitoneum will be established and maintained at a pressure of around 12-14 mm Hg by an automatic insufflation until the completion of surgery.

Normothermia will be maintained during the operation and Ringer Lactate solution will be administered in a maintenance dose according to volume requirements and blood loss.

Patients will be placed in supine position with 15° left lateral tilt and 30° head elevation.

Sevoflurane will be discontinued 10 minutes before the end of surgery.

The neuromuscular block will be reversed with neostigmine 0.05 mg/kg and glycopyrolate 0.008 mg/kg intravenously and patients will be extubated following fulfillment of extubation criteria.

Patient’s HR, SBP, DBP, MAP will be observed at baseline then following administration of study drug, induction , intubation, following pneumoperitoneum, then at interval of 5min, 10min, 15min, 30 min, 45 min, 60 min,75 min, 90 min then every half an hour till surgery continues and at last till 10 minutes post extubation. Patients will be assessed for postoperative analgesia following extubation at 30 minutes, 2 hour, 4 hour, 6 hour, 8 hour then every four hourly till 24 hours. Rescue analgesia will be given in the form of Inj. P.C.M 1gm intravenously when VAS > 4 or on patient’s demand. Patient will also be observed for Pulse, SBP, DBP and complication, if any.

VISUAL ANALOGUE SCALE

DATA ANALYSIS:

All observations will be recorded and results will be an analyzed statistically. Data will be entered in Microsoft excel and analyzed using students t- test. Numerical data will be expressed as mean ±SD. P value ≤ 0.05 will be interpreted as clinically significant

STUDY END POINTS :

The study involves observation of effect of Magnesium sulfate versus Fentanyl for attenuation of pneumoperitoneum induced hemodynamic changes in laparoscopic cholecystectomy. We will observe the patient for 24 hours post operatively for complications if any.