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

• ClinicalTrials.gov Identifier: NCT02964416
• Recruitment Status: Completed
• First Posted: November 16, 2016
• Results First Posted: August 4, 2020
• Last Update Posted: August 4, 2020
• Sponsor: Aga Khan University
• Information provided by (Responsible Party): Asma Abdus Salam, Aga Khan University

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.

Condition or disease	Intervention/treatment	Phase
Brain Neoplasm	Drug: Injection Tramadol; Other: placebo	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Effect of Single Dose of Tramadol on Extubation Response and Quality of Emergence(Cough and Nausea Vomiting) Following Supratentorial Intracranial Surgery
• Actual Study Start Date: March 2016
• Actual Primary Completion Date: March 2018
• Actual Study Completion Date: December 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Tramadol; 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	Drug: Injection Tramadol; Other Name: Tramal
Placebo Comparator: Placebo; 0.9% Normal saline in 10 cc syringe,1ml/10kg via intravenous route, once at the time of dura closure	Other: placebo; 0.9% Normal saline in 10 ml syringe; Other Name: normal saline

Outcome Measures

Primary Outcome Measures :

1. Haemodynamic Parameters at the Time of Emergence and Postextubation [ Time Frame: Systolic BP from the time of extubation till 6 hours post operatively ]
   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.
2. Haemodynamic Parameters at the Time of Emergence and Postextubation [ Time Frame: HR from the time of extubation till 6 hours post operatively ]
   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.
3. Haemodynamic Parameters at the Time of Emergence and Postextubation [ Time Frame: Diastolic BP from the time of extubation till 6 hours post operatively ]
   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 :

1. Measure the Quality of Emergence From General Anaesthesia by Measuring the Frequency of Cough on Cough Scale. [ Time Frame: Cough at the time of emergence ]

   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.
2. Measure the Quality of Emergence From General Anaesthesia by Measuring the Frequency of Laryngospasm and Bronchospasm. [ Time Frame: at the time of extubation till 6 hours postoperatively ]
   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
3. Measure the Quality of Emergence From General Anaesthesia by Measuring Sedation Score [ Time Frame: at the time of extubation till 6 hours postoperatively ]

   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)

4. Effect of Tramadol on Quality of Emergence Measured by Extubation Response Through Monitoring PONV [ Time Frame: at Recovery Room , 2, 4 and 6 hours postoperatively ]
   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
5. Effect of Tramadol on Quality of Emergence Measured by Extubation Response Through Monitoring Convulsions [ Time Frame: at Recovery Room, 2, 4 and 6 hours postoperatively ]
   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.
6. Effect of Tramadol on Quality of Emergence Measured by Extubation Response Through Monitoring GCS [ Time Frame: at Recovery Room, 2, 4 and 6 hours postoperatively ]

   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

7. Effect of Tramadol on Quality of Emergence Measured by Extubation Response Through Mointoring Requirement of Analgesia [ Time Frame: At Recovery room, 2, 4 and 6 hours postoperatively ]
   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.
8. Measure the Quality of Emergence From General Anaesthesia by Measuring the Frequency of Episodes of Denaturation [ Time Frame: at the time of extubation ]

   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

Pakistan

Aga Khan University

Karachi, Sindh, Pakistan, 74800

Sponsors and Collaborators

Aga Khan University

Investigators

• Principal Investigator: Asma A Salam, MCPS, FCPS; Aga Khan University

  Study Documents (Full-Text)

Documents provided by Asma Abdus Salam, Aga Khan University:

Study Protocol and Statistical Analysis Plan  [PDF] April 5, 2016

More Information

Publications:

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.

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.

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.

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.

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.

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.

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.

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.

• Responsible Party: Asma Abdus Salam, Senior Instructor, Aga Khan University
• ClinicalTrials.gov Identifier: NCT02964416
• Other Study ID Numbers: 2954-Ane-ERC-14
• First Posted: November 16, 2016
• Results First Posted: August 4, 2020
• Last Update Posted: August 4, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Asma Abdus Salam, Aga Khan University:

supratentorial craniotomy; extubation response; emergence; tramadol

Additional relevant MeSH terms:

Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tramadol; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents