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Single Dose Tramadol Effect on Extubation Response and Quality of Emergence Post-supratentorial Intracranial Surgery

Primary Purpose

Brain Neoplasm

Status
Completed
Phase
Phase 4
Locations
Pakistan
Study Type
Interventional
Intervention
Injection Tramadol
placebo
Sponsored by
Aga Khan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Brain Neoplasm focused on measuring supratentorial craniotomy, extubation response, emergence, tramadol

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with craniotomy for supratentorial tumors under general anesthesia
  • American Society of Anaesthesiologists (ASA) 2 and stable ASA 3 patients
  • Elective surgery
  • Patients with Glasgow Coma Scale (GCS) 15/15

Exclusion Criteria:

  • Patients with a history of allergy or hypersensitivity to tramadol.
  • History of epilepsy or convulsions due to any reason.
  • Chronic usage of analgesic drugs.
  • Patients using monoamine oxidase inhibitors.
  • Patients with clinical signs of raised ICP.
  • Obesity (women with a body mass index >35 kg/m2 or men with a body mass index >42 kg/m2)
  • Language barrier.
  • Patients taking B-blockers or Ca channel blockers.
  • Patients above 65 years of age ( Physiology difference)

Sites / Locations

  • Aga Khan University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Tramadol

Placebo

Arm Description

Injection Tramadol 100mg diluted in 10 cc syringe (10mg/ml) to be given as 1mg/kg or (1ml/10kg) via intravenous route, once, at the time of dura closure

0.9% Normal saline in 10 cc syringe,1ml/10kg via intravenous route, once at the time of dura closure

Outcomes

Primary Outcome Measures

Haemodynamic Parameters at the Time of Emergence and Postextubation
Systolic blood pressure will be recorded at 1 minute before giving the reversal (glycopyrolate and neostigmine) and then 1,2,5,10,20,30 minutes ,1,2,4 and 6 hours after extubation. If values of blood pressure rise more than 20% from baseline values injection Metoprolol 1mg (beta blocker) bolus will be used and titrated according to response. The study will end at 6 hours post extubation.
Haemodynamic Parameters at the Time of Emergence and Postextubation
Heart rate will be recorded at 1 minute before giving the reversal (glycopyrolate and neostigmine) and then 1,2,5,10,20,30 minutes ,1,2,4 and 6 hours after extubation. If haemodynamic values of heart rate rise more than 20% from baseline values injection Metoprolol 1mg (beta blocker) bolus will be used and titrated according to response. The study will end at 6 hours post extubation.
Haemodynamic Parameters at the Time of Emergence and Postextubation
Diastolic blood pressure will be recorded at 1 minute before giving the reversal (glycopyrolate and neostigmine) and then 1,2,5,10,20,30 minutes ,1,2,4 and 6 hours after extubation. If values of blood pressure rise more than 20% from baseline values injection Metoprolol 1mg (beta blocker) bolus will be used and titrated according to response. The study will end at 6 hours post extubation.

Secondary Outcome Measures

Measure the Quality of Emergence From General Anaesthesia by Measuring the Frequency of Cough on Cough Scale.
Cough will be described on following scale 5 = No coughing or straining, 4 = Very smooth minimal coughing, 3 = Moderate coughing, 2 = Marked coughing or straining, 1 = Poor extubation Cough will be recorded on the above mentioned scale by resident/consultant at following time intervals of emergence At resumption of spontaneous breathing, Ability to respond to verbal commands At cuff deflation At extubation 2 minutes after extubation. It will be noted if it occurs during emergence at the above mentioned time intervals. Absence of it will be considered as smooth emergence.
Measure the Quality of Emergence From General Anaesthesia by Measuring the Frequency of Laryngospasm and Bronchospasm.
If there is any episode of bronchospasm or laryngospasm, it will be noted if it occured during emergence and for 6 hours post operatively. Absence of it will be considered as smooth emergence
Measure the Quality of Emergence From General Anaesthesia by Measuring Sedation Score
If there is any episode of sedation it will be noted if it occurs during emergence and for 6 hours post operatively. Absence of it will be considered as smooth emergence. sedation score will be used as 0= no sedation, 1= mildly sedated (eye opening on verbal commands), 2= moderately sedated ( awakens on giving pain), 3= deeply sedated ( not waking up even on pain)
Effect of Tramadol on Quality of Emergence Measured by Extubation Response Through Monitoring PONV
Post operative nausea vomiting will be recorded at RR, 2, 4 and 6 hours postoperatively. If there is any episode of PONV it will be noted. Absence of it will be considered as smooth emergence
Effect of Tramadol on Quality of Emergence Measured by Extubation Response Through Monitoring Convulsions
Convulsions will be recorded at Recovery Room, 2, 4 and 6 hours postoperatively.If there is any episode of convulsion, it will be noted. Absence of it will be considered as smooth emergence.
Effect of Tramadol on Quality of Emergence Measured by Extubation Response Through Monitoring GCS
Post operative Glasgow Coma Scale (GCS) will be recorded at Recovery Room, 2, 4 and 6 hours postoperatively. If there is any deterioration in GCS less than 8/15, Patients will be intubated. GCS categories <8 Low GCS 9-12 Intermediate GCS 13-15 Full GCS
Effect of Tramadol on Quality of Emergence Measured by Extubation Response Through Mointoring Requirement of Analgesia
Requirement of analgesia will be recorded at recovery room, 2, 4 and 6 hours postoperatively. If there is any need of analgesic, it will be noted and will be considered as one of the determinants of poor quality of emergence.
Measure the Quality of Emergence From General Anaesthesia by Measuring the Frequency of Episodes of Denaturation
If there is any episodes of denaturation (Oxygen saturation <92%), it will be noted it it is occurring during emergence. Absence of it will be considered as smooth emergence

Full Information

First Posted
September 19, 2016
Last Updated
July 21, 2020
Sponsor
Aga Khan University
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1. Study Identification

Unique Protocol Identification Number
NCT02964416
Brief Title
Single Dose Tramadol Effect on Extubation Response and Quality of Emergence Post-supratentorial Intracranial Surgery
Official Title
Effect of Single Dose of Tramadol on Extubation Response and Quality of Emergence(Cough and Nausea Vomiting) Following Supratentorial Intracranial Surgery
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
March 2016 (Actual)
Primary Completion Date
March 2018 (Actual)
Study Completion Date
December 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Aga Khan University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Several modalities have been studied to prevent coughing during emergence, including extubation in a deep plane of anesthesia but have proved to be unreliable. So far, no reliable method is recommended as standard of care. The advantages of administering tramadol includes a long duration of action, rapid recovery, limited depression of respiratory function and no effect on platelet makes it a safe medication to use for neurosurgical patients after craniotomy. The primary objective of the study is to observe the effect of single dose of tramadol (1mg/kg) administered 45 minutes before extubation on hemodynamic response (measurement of B.P and H.R) during extubation.
Detailed Description
Extubation after intracranial tumor surgery is desirable in order to make an early diagnosis of intracranial complications. Extubation however, may be associated with haemodynamic and metabolic changes e.g. agitation, increased oxygen consumption, catecholamine secretion, hypercapnia and systemic hypertension. These changes cause cerebral hyperemia, intracranial hypertension leading to cerebral oedema or haemorrhage, thus it is important to have smooth extubation with minimal haemodynamic and metabolic effects. Incidence of coughing on emergence from general anesthesia ranges from 38% to 96%. This may also result in postoperative intracranial hemorrhage, intracranial hypertension, cerebral edema or intraocular hypertension.This can be detrimental in neurosurgery. Several modalities have been studied to prevent coughing during emergence, including extubation in a deep plane of anesthesia but have proved to be unreliable. So far, no reliable method is recommended as standard of care. Tramadol, a synthetic opioid of the aminocyclohexanes group, is a centrally acting opioid analgesic that is used to treat moderate-to-severe pain and has an inhibitory effect on M1 and M3 muscarinic receptors. It also reduces the incidence of cough and improves extubation quality, and provides more stable haemodynamics during emergence. It neither causes respiratory depression, nor affects intracranial pressure (ICP) and cerebral perfusion pressure (CPP). Other potential advantage of administering tramadol includes a long duration of action, rapid recovery, limited depression of respiratory function and no effect on platelets thus making it a safe medication to use for neurosurgical patients after craniotomy. The onset of effect following a single dose is 3 to 5 minutes with peak effect at 45 minutes. Aim of doing this study is to observe the effect of a single dose of tramadol on quality of tracheal extubation as judged by incidence of coughing and haemodynamic changes at emergence from anesthesia. OBJECTIVE: Primary Objective: To observe the effect of single dose of tramadol (1mg/kg) administered 45 minutes before extubation on haemodynamic response (measurement of B.P and H.R) during extubation. Secondary Objective: To measure the quality of emergence from general anaesthesia by measuring the frequency of cough, laryngospasm and episodes of desaturation. OPERATIONAL DEFINITION: Emergence Period: This will be defined as the time from the recovery of spontaneous breathing after giving reversal to tracheal extubation. Quality of emergence: Good quality emergence will be defined as extubation not associated with coughing, bucking, tachycardia, hypertension, laryngospasm or bronchospasm. Tachycardia and hypertension: Rise in heart rate and blood pressure more than 20% from baseline value. Extubation response: Physiological response related to blood pressure and heart rate during extubation of trachea is called extubation response, HYPOTHESIS: Tramadol obtunds haemodynamic and cough response to extubation and thus results in good quality emergence after supratentorial craniotomy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Neoplasm
Keywords
supratentorial craniotomy, extubation response, emergence, tramadol

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tramadol
Arm Type
Experimental
Arm Description
Injection Tramadol 100mg diluted in 10 cc syringe (10mg/ml) to be given as 1mg/kg or (1ml/10kg) via intravenous route, once, at the time of dura closure
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
0.9% Normal saline in 10 cc syringe,1ml/10kg via intravenous route, once at the time of dura closure
Intervention Type
Drug
Intervention Name(s)
Injection Tramadol
Other Intervention Name(s)
Tramal
Intervention Type
Other
Intervention Name(s)
placebo
Other Intervention Name(s)
normal saline
Intervention Description
0.9% Normal saline in 10 ml syringe
Primary Outcome Measure Information:
Title
Haemodynamic Parameters at the Time of Emergence and Postextubation
Description
Systolic blood pressure will be recorded at 1 minute before giving the reversal (glycopyrolate and neostigmine) and then 1,2,5,10,20,30 minutes ,1,2,4 and 6 hours after extubation. If values of blood pressure rise more than 20% from baseline values injection Metoprolol 1mg (beta blocker) bolus will be used and titrated according to response. The study will end at 6 hours post extubation.
Time Frame
Systolic BP from the time of extubation till 6 hours post operatively
Title
Haemodynamic Parameters at the Time of Emergence and Postextubation
Description
Heart rate will be recorded at 1 minute before giving the reversal (glycopyrolate and neostigmine) and then 1,2,5,10,20,30 minutes ,1,2,4 and 6 hours after extubation. If haemodynamic values of heart rate rise more than 20% from baseline values injection Metoprolol 1mg (beta blocker) bolus will be used and titrated according to response. The study will end at 6 hours post extubation.
Time Frame
HR from the time of extubation till 6 hours post operatively
Title
Haemodynamic Parameters at the Time of Emergence and Postextubation
Description
Diastolic blood pressure will be recorded at 1 minute before giving the reversal (glycopyrolate and neostigmine) and then 1,2,5,10,20,30 minutes ,1,2,4 and 6 hours after extubation. If values of blood pressure rise more than 20% from baseline values injection Metoprolol 1mg (beta blocker) bolus will be used and titrated according to response. The study will end at 6 hours post extubation.
Time Frame
Diastolic BP from the time of extubation till 6 hours post operatively
Secondary Outcome Measure Information:
Title
Measure the Quality of Emergence From General Anaesthesia by Measuring the Frequency of Cough on Cough Scale.
Description
Cough will be described on following scale 5 = No coughing or straining, 4 = Very smooth minimal coughing, 3 = Moderate coughing, 2 = Marked coughing or straining, 1 = Poor extubation Cough will be recorded on the above mentioned scale by resident/consultant at following time intervals of emergence At resumption of spontaneous breathing, Ability to respond to verbal commands At cuff deflation At extubation 2 minutes after extubation. It will be noted if it occurs during emergence at the above mentioned time intervals. Absence of it will be considered as smooth emergence.
Time Frame
Cough at the time of emergence
Title
Measure the Quality of Emergence From General Anaesthesia by Measuring the Frequency of Laryngospasm and Bronchospasm.
Description
If there is any episode of bronchospasm or laryngospasm, it will be noted if it occured during emergence and for 6 hours post operatively. Absence of it will be considered as smooth emergence
Time Frame
at the time of extubation till 6 hours postoperatively
Title
Measure the Quality of Emergence From General Anaesthesia by Measuring Sedation Score
Description
If there is any episode of sedation it will be noted if it occurs during emergence and for 6 hours post operatively. Absence of it will be considered as smooth emergence. sedation score will be used as 0= no sedation, 1= mildly sedated (eye opening on verbal commands), 2= moderately sedated ( awakens on giving pain), 3= deeply sedated ( not waking up even on pain)
Time Frame
at the time of extubation till 6 hours postoperatively
Title
Effect of Tramadol on Quality of Emergence Measured by Extubation Response Through Monitoring PONV
Description
Post operative nausea vomiting will be recorded at RR, 2, 4 and 6 hours postoperatively. If there is any episode of PONV it will be noted. Absence of it will be considered as smooth emergence
Time Frame
at Recovery Room , 2, 4 and 6 hours postoperatively
Title
Effect of Tramadol on Quality of Emergence Measured by Extubation Response Through Monitoring Convulsions
Description
Convulsions will be recorded at Recovery Room, 2, 4 and 6 hours postoperatively.If there is any episode of convulsion, it will be noted. Absence of it will be considered as smooth emergence.
Time Frame
at Recovery Room, 2, 4 and 6 hours postoperatively
Title
Effect of Tramadol on Quality of Emergence Measured by Extubation Response Through Monitoring GCS
Description
Post operative Glasgow Coma Scale (GCS) will be recorded at Recovery Room, 2, 4 and 6 hours postoperatively. If there is any deterioration in GCS less than 8/15, Patients will be intubated. GCS categories <8 Low GCS 9-12 Intermediate GCS 13-15 Full GCS
Time Frame
at Recovery Room, 2, 4 and 6 hours postoperatively
Title
Effect of Tramadol on Quality of Emergence Measured by Extubation Response Through Mointoring Requirement of Analgesia
Description
Requirement of analgesia will be recorded at recovery room, 2, 4 and 6 hours postoperatively. If there is any need of analgesic, it will be noted and will be considered as one of the determinants of poor quality of emergence.
Time Frame
At Recovery room, 2, 4 and 6 hours postoperatively
Title
Measure the Quality of Emergence From General Anaesthesia by Measuring the Frequency of Episodes of Denaturation
Description
If there is any episodes of denaturation (Oxygen saturation <92%), it will be noted it it is occurring during emergence. Absence of it will be considered as smooth emergence
Time Frame
at the time of extubation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with craniotomy for supratentorial tumors under general anesthesia American Society of Anaesthesiologists (ASA) 2 and stable ASA 3 patients Elective surgery Patients with Glasgow Coma Scale (GCS) 15/15 Exclusion Criteria: Patients with a history of allergy or hypersensitivity to tramadol. History of epilepsy or convulsions due to any reason. Chronic usage of analgesic drugs. Patients using monoamine oxidase inhibitors. Patients with clinical signs of raised ICP. Obesity (women with a body mass index >35 kg/m2 or men with a body mass index >42 kg/m2) Language barrier. Patients taking B-blockers or Ca channel blockers. Patients above 65 years of age ( Physiology difference)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Asma A Salam, MCPS, FCPS
Organizational Affiliation
Aga Khan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aga Khan University
City
Karachi
State/Province
Sindh
ZIP/Postal Code
74800
Country
Pakistan

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
8638792
Citation
Mikawa K, Nishina K, Maekawa N, Obara H. Attenuation of cardiovascular responses to tracheal extubation: verapamil versus diltiazem. Anesth Analg. 1996 Jun;82(6):1205-10. doi: 10.1097/00000539-199606000-00018.
Results Reference
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PubMed Identifier
22089326
Citation
Lin BF, Ju DT, Cherng CH, Hung NK, Yeh CC, Chan SM, Wu CT. Comparison between intraoperative fentanyl and tramadol to improve quality of emergence. J Neurosurg Anesthesiol. 2012 Apr;24(2):127-32. doi: 10.1097/ANA.0b013e31823c4a24.
Results Reference
background
PubMed Identifier
10195515
Citation
Valley RD, Ramza JT, Calhoun P, Freid EB, Bailey AG, Kopp VJ, Georges LS. Tracheal extubation of deeply anesthetized pediatric patients: a comparison of isoflurane and sevoflurane. Anesth Analg. 1999 Apr;88(4):742-5. doi: 10.1097/00000539-199904000-00010.
Results Reference
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PubMed Identifier
8024135
Citation
Neelakanta G, Miller J. Minimum alveolar concentration of isoflurane for tracheal extubation in deeply anesthetized children. Anesthesiology. 1994 Apr;80(4):811-3. doi: 10.1097/00000542-199404000-00013.
Results Reference
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PubMed Identifier
11452859
Citation
Ferber J, Juniewicz H, Glogowska E, Wronski J, Abraszko R, Mierzwa J. Tramadol for postoperative analgesia in intracranial surgery. Its effect on ICP and CPP. Neurol Neurochir Pol. 2000;34(6 Suppl):70-9.
Results Reference
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PubMed Identifier
17506732
Citation
Sudheer PS, Logan SW, Terblanche C, Ateleanu B, Hall JE. Comparison of the analgesic efficacy and respiratory effects of morphine, tramadol and codeine after craniotomy. Anaesthesia. 2007 Jun;62(6):555-60. doi: 10.1111/j.1365-2044.2007.05038.x.
Results Reference
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PubMed Identifier
19630495
Citation
Rahimi SY, Alleyne CH, Vernier E, Witcher MR, Vender JR. Postoperative pain management with tramadol after craniotomy: evaluation and cost analysis. J Neurosurg. 2010 Feb;112(2):268-72. doi: 10.3171/2008.9.17689.
Results Reference
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PubMed Identifier
10235420
Citation
Lintz W, Beier H, Gerloff J. Bioavailability of tramadol after i.m. injection in comparison to i.v. infusion. Int J Clin Pharmacol Ther. 1999 Apr;37(4):175-83.
Results Reference
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Single Dose Tramadol Effect on Extubation Response and Quality of Emergence Post-supratentorial Intracranial Surgery

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