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CTRI Number  CTRI/2020/01/022983 [Registered on: 27/01/2020] Trial Registered Prospectively
Last Modified On: 15/01/2020
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Drug
Surgical/Anesthesia 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   A clinical based study to find out the exact lowest possible dose of ketamine, a drug which takes care of the pain and also helps in maintaining the state of anaesthesia during surgery, in keeping the patient pain free in the period after Laparoscopic Cholecystectomy surgery. 
Scientific Title of Study   A Parallel Group, Double-Blind, Randomized Controlled Trial to assess the optimum dose of ketamine infusion in management of early postoperative pain in Elective Laparoscopic Cholecystectomy 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  John Christian S 
Designation  Post Graduate Trainee 
Affiliation  Dept. of Anaesthesiology, Midnapore Medical College 
Address  Dept. of Anaesthesiology, Midnapore Medical College, Midnapore, Paschim Medinipur. Medinipur

Medinipur
WEST BENGAL
721101
India 
Phone  9944911771  
Fax    
Email  johnchris.sam@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Bani Parvati Magda Hembrom 
Designation  Associate Professor 
Affiliation  Dept. of Anaesthesiology, Midnapore Medical College 
Address  Dept. of Anaesthesiology, Midnapore Medical College, Midnapore, Paschim Medinipur. Medinipur
Dept. of Anaesthesiology, Midnapore Medical College, Midnapore, Paschim Medinipur. Medinipur
Medinipur
WEST BENGAL
721101
India 
Phone  9903207690  
Fax    
Email  banihembrom72@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Bani Parvati Magda Hembrom 
Designation  Associate Professor 
Affiliation  Dept. of Anaesthesiology, Midnapore Medical College 
Address  Dept. of Anaesthesiology, Midnapore Medical College, Midnapore, Paschim Medinipur. Medinipur
Dept. of Anaesthesiology, Midnapore Medical College, Midnapore, Paschim Medinipur. Medinipur
North Twentyfour Parganas
WEST BENGAL
721101
India 
Phone  9903207690  
Fax    
Email  banihembrom72@gmail.com  
 
Source of Monetary or Material Support  
Office of the Principal, Midnapore Medical College, Govt. of West Bengal, Vidyasagar Road, Paschim Medinipur-721101 
 
Primary Sponsor  
Name  Midnapore Medical College 
Address  Midnapore, Paschim Medinipur. Pin 721101 
Type of Sponsor  Government medical college 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
John Christian S  General surgery operation theatre complex with post-operative care unit  Operation Theatre A, Surgical OT Complex, Department of Surgery, Bidhan Block, Midnapore Medical College, Vidyasagar Road, Midnapore, Paschim Medinipur- 721101
Medinipur
WEST BENGAL 
9944911771

johnchris.sam@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: K802||Calculus of gallbladder without cholecystitis,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  35 Patients undergoing elective laparoscopic cholecystectomy will recieve an equivalent dose of normal saline (Group N)  The patients undergoing elective Laparoscopic Cholecystectomy under General Anaesthesia will be started with the intravenous test drug from the start of abdominal port placement till the end of skin closure. Other steps of general anaesthesia are followed as per routine standards. Following the surgery patients will be observed in Post Anaesthesia Care Unit for 4 hours and then upon shifting to post operative ward will be followed up for the next 24 hours and assessed 
Intervention  Patients undergoing elective laparoscopic cholecystectomy will be allotted into 3 subgroups with 35 patients each and will recieve 20 mcg/kg/min (Group K1), 30 mcg/kg/min (Group K2) & 40 mcg/kg/min (Group K3) respectively  The patients undergoing elective Laparoscopic Cholecystectomy under General Anaesthesia will be started with the intravenous test drug from the start of abdominal port placement till the end of skin closure. Other steps of general anaesthesia are followed as per routine standards. Following the surgery patients will be observed in Post Anaesthesia Care Unit for 4 hours and then upon shifting to post operative ward will be followed up for the next 24 hours and assessed 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  1) Age group between 18-65 years.
2) ASA grade I to II.
3) Patients posted for Elective laproscopic cholecystectomy under General 
 
ExclusionCriteria 
Details  1) Psychiatric disorders such as schizophrenia and acute psychoses.
2) Patients with features of raised IntraCranial Pressure
3) Penetrating Eye injury and increased IntraOcular Pressure.
4) Regular use of anti-inflammatory drugs (NSAIDs)
5) Chronic pain syndromes
6) Acute or chronic alcohol intoxication
7) Chronic kidney disease, Chronic Liver disease
8) Moderate to severe hypertension 9) Acute Porphyria
10) History of CErebroVascular accident
11) Intolerance or allergy to S(+)-ketamine
12) Any patients below 18 years old and above 65 years old
13) Any drug allergy.
14) Any emergency surgery. 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Participant, Investigator and Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
1. To assess the effectiveness of different doses of intraoperative ketamine infusion for post operative analgesia in reducing the need for rescue analgesic requirement.
2.To assess the time of requirement of first rescue analgesic dose in each individual groups. 
During the period of next 24 hours following the surgery 
 
Secondary Outcome  
Outcome  TimePoints 
observation of change in hemodyanamic profile in either groups upon administering of the test drug  throughout the surgery duration 
 
Target Sample Size   Total Sample Size="140"
Sample Size from India="140" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   N/A 
Date of First Enrollment (India)   01/02/2020 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary  

BACKGROUND OF RESEARCH:

In the developing world, Ketamine is a vital and highly valued drug that allows performance of interventions and operations that may otherwise prove impossible, especially when resources are limited. Ketamine is one of the most available anaesthetic agents in low- to middle-income countries (LMICs)[1].

With the recent developments of anesthetic and newer surgical techniques and a need to reduce costs, surgeries such as laparoscopic cholecystectomy are now performed with minimal hospital stay or done as outpatient services. Delayed hospital discharge is mainly due to the intensity of postoperative pain and the occurrence of nausea or vomiting. Inadequate management of postoperative pain in laproscopic cholecystectomy can lead to negative consequences such as late mobilization with consequent delay in discharge development of chronic pain and increased treatment costs.

Ketamine, an NMDA (N-methyl-D-Aspartate) receptor antagonist is a potent analgesic and a dissociative anaesthetic agent used in anaesthetic procedures in a routine. It’s newly found neuro-protective, anti-inflammatory and anti-tumor effects, and the finding of the usefulness of low dose ketamine regimens have helped to widen the clinical application profile of ketamine.

In Developing World, Ketamine is currently used extensively due to its versatility, availability and low side-effect profile. There has been discussion about its potential for misuse and whether greater controls worldwide are required.

Fewer notable newer mechanisms of action ketamine,

i. NMDA receptor interaction with ketamine plays a role in the opioid induced anti-hyperalgesic effects of ketamine[2]

ii. Its anti-pro-inflammatory effects may be responsible for its antihyperalgesic effects[2].

iii. Its immediate analgesic effects are mediated predominantly by a combination of opioid system sensitization and anti-nociception[3]

iv. Sub-anesthetic doses of ketamine via NMDA receptor blockade potentiate opioid analgesia[4]

Dipti et al. on using low dose ketamine as a sole anaesthetic agent in laproscopic gynecological surgeries found out that low dose ketamine has efficacious analgesic effect in long duration laproscopic gynecological surgeries and also stabilises the intraoperative hemodyanamics[5].

Harsimran et al. Studied on preemptive analgesia with ketamine for laproscopic cholecystectomy found that ketamine has a definitive role in reducing postoperative pain and analgesic requirement and also the lower dosage is devoid of the adverse effects and hemodyanamic changes in optimal dose[6].

Ozhan et al. on comparing sub anaesthetic doses of ketamine in scheduled cases of laproscopic cholecystectomy found out that there is decrease in need of total analgesic consumption in postoperative period and Cognitive functions at 24th postoperative hour were identical to those at baseline[7].

 

STEPS OF STUDY PROCEDURE

I. Preoperative evaluation

II. PREMEDICATIONS -Inj. Glycopyrolate 10mcg/kg

Inj. Fentanyl 2mcg/kg ( 5mins before induction)

III. PREOXYGENATION x 3 mins

IV. INDUCTION  -Inj Propofol 2mg/kg

V. INTUBATIOIN FOLLOWING Inj Atracurium 0.5mg/kg

VI. 1. INFUSION OF TEST DRUG with syringe pump with 50 ml syringe containing preloaded prefixed dose of test drug

2. Inf Paracetamol 15mg/kg

VII. MAINTAINENCE - N2O:02  = 7:3

ISOFLURANE @ 0.5 - 1 MAC

Inj Atracurium 0.2mg/kg

VIII. INTRAOPERATIVE DRUGS- Inf. RL/NS

Inj Ondanseteran 4mg (30mins before end of surgery)

IX. Stop maintainence doses and test drug at end of skin closure

X. Extubatation with Inj. Neostigmine 0.5mg/kg + Inj Glycopyrolate 0.2mg/kg

XI. Shift to PACU after reversal and follow-up

XII. Shift to Post-operative unit in surgical ward after 4 hours and follow-up

XIII. Follow up till 24hours with documentation of study parameters and interventions the case proforma

 

EXPECTED OUTCOME :  By using different doses of ketamine the optimal dose to use in a day today practice in Laproscopic Cholecystectomy patients with the decrease in adverse effects of ketamine itself and also achieving a of better haemodynamic and postoperative outcome with a decrease in need of intervention in postoperative period will be evaluated. Using a placebo centered group will show the effectiveness of performing the study with infusion ketamine intraoperatively.

 

REFERENCES:

1. Dong TT, Mellin-Olsen J, Gelb AW. Ketamine: a growing global health-care need. Br J Anaesth. 2015;115(4):491-493.

2. Persson J. Wherefore ketamine? Curr Opin Anaesthesiol. 2010;23:455–60.

3. Sleigh J, Harvey M, Voss L, Denny B. Ketamine-more mechanisms of action than just NMDA blockade. Trends Anaesth Crit Care. [In press]

4. Hirota K, Lambert DG. Ketamine: New uses for an old drug? Br J Anaesth. 2011;107:123–6.

5. Saxena D, Dixit A, Kumar N, Arya B, Sanwatsarkar S, Bhandari S. Efficacy of low-dose ketamine as sole analgesic agent in maintaining analgesia and intraoperative

hemodynamics during laparoscopic gynecological surgeries. Anesth Essays Res

2017;11:385-9

6. Singh, Harsimran & Kundra, Sandeep & M Singh, Rupinder & Grewal, Anju & K Kaul, Tej & Sood, Dinesh. (2013). Preemptive analgesia with Ketamine for Laparoscopic cholecystectomy. Journal of anaesthesiology, clinical pharmacology. 29. 478-84. 10.4103/0970-9185.119141.

7. Ozhan Y, Bakan N, Karaoren GY, Tomruk SG, Topaç Z. Effects of subanesthetic

ketamine on pain and cognitive functions in TIVA. J Clin Anal Med. 015;6(4):452-7.

 

 

 
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