Opioid Free VS Opioid Anesthesia for Craniotomies

NCT ID: NCT04941040

Last Updated: 2021-10-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-05

Study Completion Date

2021-10-03

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Supratentorial Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Opioid free anesthesia

patients are going to receive intraoperative analgesics other than opioids

Group Type EXPERIMENTAL

Opioid free anesthetics

Intervention Type DRUG

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 anesthesia

patients are going to receive intraoperative opioid analgesics

Group Type ACTIVE_COMPARATOR

Opioid Anesthetics

Intervention Type DRUG

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.

Interventions

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Opioid free anesthetics

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

Intervention Type DRUG

Opioid Anesthetics

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.

Intervention Type DRUG

Other Intervention Names

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OFA OA

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* Impaired renal functions.
* Systemic hypertension.
* Dysrhythmia.
* Heart failure.
* Glasgow coma scale less than 12.
* The need for postoperative ventilation.
* History of allergy to the study drugs.
* Surgeries lasting more than 6 hours.
* Pregnancy.
* Bronchial asthma
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kasr El Aini Hospital

OTHER

Sponsor Role lead

Responsible Party

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Rania Samir Fahmy

Assistant professor of Anesthesia, ICU and pain medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Rania S Fahmy

Role: PRINCIPAL_INVESTIGATOR

Kasr Al Ainy, Faculty of medicine, Cairo university

Locations

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Kasr El Aini Hospital

Cairo, , Egypt

Site Status

Countries

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Egypt

References

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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.

Reference Type BACKGROUND
PMID: 18580347 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10861145 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 16508405 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26595546 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15505442 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19138915 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33171574 (View on PubMed)

Other Identifiers

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N 56-2016/MD

Identifier Type: -

Identifier Source: org_study_id