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Supratentorial NeoplasmsPhase 1NCT04941040

Opioid Free VS Opioid Anesthesia for Craniotomies

A Phase 1 study testing Opioid free anesthetics and Opioid Anesthetics in people with Supratentorial Neoplasms, run by Kasr El Aini Hospital at 1 site in Egypt.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Hemodynamic control during craniotomies can be a bit hectic specially during periods of intense noxious stimulation. For long anesthesiologists used high doses of opioids such as fentanyl and remifentanyl to provide analgesia with a good hemodynamic control during intraoperative period in patients undergoing… Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Supratentorial Neoplasms
What is being tested?
Opioid free anesthetics and Opioid Anesthetics
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteEgypt
Study dates
5 Jul 2021to 3 Oct 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • ASA Ι and II.
  • Patients undergoing surgeries for removal of supratentorial tumors.
  • Age (18-60) years.
  • Both sexes.

Who cannot join

  • Impaired renal functions.
  • Systemic hypertension.
  • Dysrhythmia.
  • Heart failure.
  • Glasgow coma scale less than 12.
  • The need for postoperative ventilation.
Show all 10Show fewer
  • History of allergy to the study drugs.
  • Surgeries lasting more than 6 hours.
  • Pregnancy.
  • Bronchial asthma

Trial locations and contacts

1 site in 1 country.

Egypt1 site
  • Kasr El Aini Hospital

    Cairo, 11687

Other trials in Egypt

About this study

Official title: Hemodynamic Effects of Opioid Free Anesthesia Versus Opioid Anesthesia on Adult Patients Undergoing Craniotomies for Supratentorial Tumors. Randomized Controlled Trial

Hemodynamic control during craniotomies can be a bit hectic specially during periods of intense noxious stimulation. For long anesthesiologists used high doses of opioids such as fentanyl and remifentanyl to provide analgesia with a good hemodynamic control during intraoperative period in patients undergoing craniotomies. However, the use of opioids was not devoid of side effects. Exploring other anesthetic plans using multiple opioid free anesthetic adjuvants that have analgesic effects given together in small doses appear to be appealing plan. This idea is the basis of our proposed study in which we compare the hemodynamic effects of using opioid free anesthesia versus opioid anesthesia in cranial surgeries.

Read the detailed description

Anesthesia for craniotomies can be very challenging because of the presence of periods of noxious stimuli that interposes with periods of little stimulation which makes hemodynamic control a little bit more complicated. Intraoperative episodes of hypertension during periods of intense stimulations and early postoperative hypertension may lead to serious complications as post craniotomy intracranial hemorrhage and vasogenic brain edema. Anesthetic techniques based on usage of high doses of potent opioid analgesics such as fentanyl and remifentanil have been widely popular among anesthesiologists. However, the intra operative use of large bolus doses or continuous infusions of potent opioids may be associated with postoperative hyperalgesia and increased analgesic consumption.

More recently, concerns have arisen about impaired healing,immunosuppression,and worsening of oncologic outcomes with systemic opioids. Another technique that started gaining its popularity is opioid free anesthesia (OFA) technique whose corner stone is depending on multiple anesthetic adjuvants that have analgesic effects, , therefore when given together in small doses they result in good anesthesia with less side effects and faster recovery compared with opioids. This technique has been successfully used in anesthesia for bariatric surgeries combining multiple drugs as dexmedetomidine, lidocaine, ketamine, ketorolac and magnesium.

Dexmedetomidine is a highly selective α2-adrenoceptor agonist with sedative, anxiolytic and analgesic properties that has minimal effects on respiratory drive. Although preoperative intravenous dexmedetomidine administration is associated with a reduction in postoperative pain intensity, analgesic consumption and nausea, the analgesic property of dexmedetomidine is less effective compared with opioids. Intravenous lidocaine has been described as having analgesic, anti-hyperalgesic, and anti-inflammatory properties. Intravenous lidocaine infusion in the perioperative period is safe and has clear advantages, such as decreased intra operative anesthetic requirements, lower pain scores, reduced postoperative analgesic requirements, as well as faster recovery. In addition to ketamine magnesium is also reported to enhance analgesia by blocking NMDA receptor, also magnesium has the properties of a sympatholytic and has been introduced as a safe component of balanced anesthesia.

This comparative study between Opioid free anesthesia (OFA) and Opioid anesthesia (OA) aims to compare the effect of both techniques on intra operative hemodynamics, intracranial tension and recovery in cranial surgeries for supratentorial tumors.

After obtaining an informed written consent from the patients or their responsible relative, patients will be divided into 2 groups randomly using computer software (research randomizer.org); Opioid free Anesthesia group (OFA) and Opioid Anesthesia group (OA). To assure blindness, numbers will be concealed by closed envelope, analgesic infusions will prepared by a clinical pharmacist not included in data collection and the attending anesthetist will be blinded to the type of analgesic solution injected.

Over 10 minutes prior to induction of analgesia patients in the OFA group will receive small doses of demedetomidine, ketamine, lidocaine and magnesium along with ketorlac and acetaminophen. an infusion afterwards will be administered through the operation containing dexmedetomidine, ketamine and lidocaine. In the OA group, over 10 minutes, patients will receive a loading dose of fentanyl followed by fentanyl infusion through the operation. General anesthesia will be induced using the same drugs and the same parameters in both groups after the completion of the initial analgesic infusions The primary outcome parameter will be the percentage of patients experiencing hemodynamic instability at Burr Hole (defined as recording an increase or decrease of the mean arterial blood pressure by 25 % of the baseline reading) Assuming the rate of hemodynamic instability (defined as increase or decrease of the mean blood pressure by 25 % of the baseline reading) would be 40 % in the control arm, a clinically meaningful reduction of the rate of hemodynamic instability to 10 % in the investigational arm with a statistical power of 80 % and an alpha error of less than 0.05 would require recruiting 29 patients in each group (a total of 58 patients).

Continuous data will be presented as mean + (SD). Categorical variables will be represented as frequencies and percentages. According to the type of data Comparison between the two groups will be performed using either Chi square test or Fisher's exact test. Hemodynamic variables will be compared to baseline using repeated measures analysis of variance (ANOVA) with post hoc scheffe's test for positive data. P values less than 0.05 will be considered statistically significant.

Being tested
Opioid free anesthetics, Opioid Anesthetics
Keywords
Opioid free Anesthesia, Craniotomies, Dexmedetomidine, Ketamine, Fentanyl, Lidocaine, Magnesium sulphate, supratentorial tumors
Medical subject headings
Supratentorial Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Opioid free anestheticsDrug

    Also called OFA

    Patients will receive over the 10 minutes prior to induction:

    • Acetaminophen 1 gm i.v. infusion in 100ml over 10 minutes.
    • Ketorolac 30 mg i.v. infusion in100 ml over 10 minutes.
    • Mg SO4 loading dose 30 mg/kg i.v. infusion in 100 ml over 10 minutes.
    • Dexmedetomidine loading dose 1 μg/kg i.v. infusion.
    • Lidocaine loading dose 1.5 mg/kg i.v. infusion.
    • Ketamine loading dose 0.25 mg/kg i.v. infusion.

    The weight based doses of dexmedetomidine, lidocaine, ketamine will be prepared on 20 ml syringe and infused over 10 minutes prior to induction. In a dose of 0.1 ml/kg

    Then after induction maintenance analgesic infusion will start in a rate that ranges from 0.025 to 0.05 ml/kg/h which is equivalent to:

    • Dexmedetomidine 0.25-0.5 μg/kg/h
    • Lidocaine 0.375-0.75 mg/kg/h
    • Ketamine 0.0625- 0.125 mg/kg/h
  • Opioid AnestheticsDrug

    Also called OA

    Placebo equivalent to acetaminophen, ketorolac, magnesium sulphate will be infused as 100 ml normal saline each over 10 minutes ,patients will receive fentanyl 2 μg/kg loading dose which will be prepared over 20 ml syringe and infused over 10 minutes prior to induction, Then after induction maintenance of analgesic infusion by fentanyl 0.5-1 μg/kg/h.

Study groups in NCT04941040
Study groupRoleWhat they receive
Opioid free anesthesiaExperimentalpatients are going to receive intraoperative analgesics other than opioids
Receives: Drug: Opioid free anesthetics
Opioid anesthesiaActive comparatorpatients are going to receive intraoperative opioid analgesics
Receives: Drug: Opioid Anesthetics

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of patients experiencing a change in mean arterial pressure at time of Burr Hole

    Defined as recording an increase or decrease of the mean arterial blood pressure by more than 25 % from baseline readings at the time of burr hole

    Measured: During Burr hole surgery

Secondary outcomes (8)
  1. HR (heart rate) in beats/min

    Hemodynamic parameter recorded during the study

    Measured: Baseline, pre-induction, pre-intubation, after intubation, skin incision, burr hole, dural incision, dural closure, skin closure, every 30 minutes intraoperative till extubation, time of extubation, every 15 minutes for 2 hours in PACU.

  2. Brain relaxation score

    Defined as 1= excellently relaxed, 2= satisfactory relaxed, 3= leveled, 4=bulging

    Measured: At the time of dural incision

  3. Number of patients requiring antihypertensive medication

    Number of patients needing nitroglycerine infusion in each group was recorded together with total amount infused

    Measured: Throughout the operation

  4. Number of patients requiring medication to increase blood pressure

    Number of patients needing ephedrine in each group was recorded together with total amount infused.

    Measured: Throughout the operation

  5. Time to extubation

    Defined as the time between the discontinuation of inhalation agents and extubation

    Measured: At the end of the operation, the time from the discontinuation of inhalation agents till extubation

  6. Ramsay Sedation Scale (RSS)

    to assess the postoperative sedation, it is a scale from 1 to 6. It provides three levels of 'awake' states (score 1-3) and three levels of 'asleep' states (score 4-6). A score of 2 (patient is cooperative, orientated and tranquil)

    Measured: every 30 minutes for 2 hours postoperative

  7. Systolic blood pressure (SBP) in mmhg

    Hemodynamic parameter recorded during the study

    Measured: Baseline, pre-induction, pre-intubation, after intubation, skin incision, burr hole, dural incision, dural closure, skin closure, every 30 minutes intraoperative till extubation, time of extubation, every 15 minutes for 2 hours in PACU.

  8. Mean arterial blood pressure (MAP) in mmhg

    Hemodynamic parameter recorded during the study

    Measured: Baseline, pre-induction, pre-intubation, after intubation, skin incision, burr hole, dural incision, dural closure, skin closure, every 30 minutes intraoperative till extubation, time of extubation, every 15 minutes for 2 hours in PACU.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jun 2021
  2. Study start5 Jul 2021
  3. Primary completion3 Oct 2021
  4. Study completion3 Oct 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04941040
Sponsor's protocol ID
N 56-2016/MD
Status last verified
Oct 2021
First submitted
12 Jun 2021
Last updated
19 Oct 2021
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Uyar AS, Yagmurdur H, Fidan Y, Topkaya C, Basar H. Dexmedetomidine attenuates the hemodynamic and neuroendocrinal responses to skull-pin head-holder application during craniotomy. J Neurosurg Anesthesiol. 2008 Jul;20(3):174-9. doi: 10.1097/ANA.0b013e318177e5eb.

    PubMed 18580347
  • Basali A, Mascha EJ, Kalfas I, Schubert A. Relation between perioperative hypertension and intracranial hemorrhage after craniotomy. Anesthesiology. 2000 Jul;93(1):48-54. doi: 10.1097/00000542-200007000-00012.

    PubMed 10861145
  • Angst MS, Clark JD. Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology. 2006 Mar;104(3):570-87. doi: 10.1097/00000542-200603000-00025.

    PubMed 16508405
  • Mulier JP. Perioperative opioids aggravate obstructive breathing in sleep apnea syndrome: mechanisms and alternative anesthesia strategies. Curr Opin Anaesthesiol. 2016 Feb;29(1):129-33. doi: 10.1097/ACO.0000000000000281.

    PubMed 26595546
  • Cortinez LI, Hsu YW, Sum-Ping ST, Young C, Keifer JC, Macleod D, Robertson KM, Wright DR, Moretti EW, Somma J. Dexmedetomidine pharmacodynamics: Part II: Crossover comparison of the analgesic effect of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology. 2004 Nov;101(5):1077-83. doi: 10.1097/00000542-200411000-00006.

    PubMed 15505442
  • Lauwick S, Kim DJ, Michelagnoli G, Mistraletti G, Feldman L, Fried G, Carli F. Intraoperative infusion of lidocaine reduces postoperative fentanyl requirements in patients undergoing laparoscopic cholecystectomy. Can J Anaesth. 2008 Nov;55(11):754-60. doi: 10.1007/BF03016348.

    PubMed 19138915
  • Syeda S, Palaniswamy SR, Sriganesh K. Opioid Free Analgesia With Dexmedetomidine for Craniotomy in an Obese Patient With Obstructive Sleep Apnea and Difficult Airway. Asian J Anesthesiol. 2020 Jun 1;58(2):76-77. doi: 10.6859/aja.202006_58(2).0007. Epub 2020 Jul 24. No abstract available.

    PubMed 33171574

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Opioid free anesthetics and Opioid Anesthetics in people with Supratentorial Neoplasms, run by Kasr El Aini Hospital at 1 site in Egypt.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of patients experiencing a change in mean arterial pressure at time of Burr Hole (time frame: During Burr hole surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04941040, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2021.

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