Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202101897491424 Date of Approval: 15/01/2021
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title caffeine speeds recovery from anesthesia
Official scientific title IMPACT OF CAFFIENE ON EMERGENCE FROM ANESTHESIA AND DISCHARGE CRITERIA IN DAY CASE SURGERIES: A PROSPECTIVE RANDOMIZED DOUBLE-BLIND PLACEBO CONTROLLED TRIAL
Brief summary describing the background and objectives of the trial The terms `ambulatory surgery', `day-case surgery' and `out-patient surgery' are used synonymously to indicate that the patient is discharged on the day of surgery without overnight hospital stay. Recent advances in anaesthetic and surgical techniques, along with escalating healthcare costs, have resulted in an ever-increasing number of surgical procedures being performed on a day-case basis world-wide. The cost effectiveness of day-case surgery is well recognized. As outcome data become available confirming the safety of day-case surgery, it is anticipated that even more procedures will be performed on a day-case basis. Most day-case surgery procedures are associated with relatively minor surgical trauma, so discharge of these patients frequently depends on recovery from anaesthesia. Top priorities for successful outpatient surgery are the four `A's: alertness, ambulation, analgesia and alimentation. Since the proportion of surgery done on an outpatient basis is increasing, and since early discharge and patient satisfaction are important goals, the previous four `A's are receiving greater attention. Currently, there is no method to accelerate emergence from anesthesia. Patients “wake” when they clear the anesthetic from their systems. In a study on rats, caffeine by complex pathways dramatically accelerated emergence from anesthesia, even at the high level of anesthetic employed. Because anesthesia in rodents is thought to be similar to that in humans, these results suggest that caffeine might allow for rapid and uniform emergence from general anesthesia in humans at all anesthetic concentrations. Although in one study intravenous caffeine enhanced the speed of recovery of heavily sedated patients in the post-anesthesia recovery area without changes in respiratory parameters or adverse cardiac events .
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Anaesthesia
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Other
Anticipated trial start date 10/05/2020
Actual trial start date 10/05/2020
Anticipated date of last follow up 16/08/2020
Actual Last follow-up date
Anticipated target sample size (number of participants) 70
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Masking/blinding used Care giver/Provider,Outcome Assessors
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group placebo control 50 ml normal saline 10 Minutes before the end of surgery Patients will be randomly assigned using randomized code (by double blind technique) into: Control group (P) (n = 35) will receive 50 ml saline infusion over 10 minutes. In the holding area, after history taking and clinical examination, baseline vital signs will be recorded. After insertion of I.V. line all patients will be premedicated with ranitidine (50 mg IV) and paracetamol (1 gm infused over 10 minutes). Standard monitoring will be maintained throughout; including electrocardiogram, blood pressure, respiratory rate, end-tidal CO2 and isoflurane levels, pulse oximetry, bispectral Index and temperature. Subjects will be preoxygenated with 100% O2 via a face mask and then given fentanyl 1.5 mic/kg and a sleeping dose of propofol to induce anesthesia. Cis-atracurium 0.15 mg/kg will be used to facilitate endotracheal intubation and mechanical ventilation followed by 0.03 mg/kg guided by TOF monitor while avoiding top up doses within the last 20 minutes of the surgical procedure. Anesthesia will be maintained by isoflurane 1.2 MAC in air:oxygen (50:50%) targeting BIS 40-50 all through the intraoperative course. Fentanyl 1 mic/kg will be given IV every 30 minutes intraoperatively. The study drug will be prepared by an anesthesia resident who is not involved in the study or care of the patient. All preventive measures against hypothermia will be done. Towards the end of surgery, ketorolac tromethamine (30 mg) will be slowly infused intravenously. At 10 min before the end of surgery, patients will receive an infusion during 10 min of either saline (control) or caffeine. The end of surgery is defined as time point zero (T0) for both groups and it corresponds to switching off isoflurane with the last skin stitch and marked the onset of the emergence time measurements. Towards the end of surgery, granisetron 1 mg will be slowly infused IV. After discontinuation of isoflurane, muscle relaxants will be reversed, and the subjects will be allowed to breathe spontaneous 35 Placebo
Experimental Group caffeine group caffeine citrate (500 mg) (Caffeinospire®) (60 mg / 3 ml vial) (20 mg / ml) (10 mg caffeine base) diluted by saline up to 50 ml once during the last 10 minutes of anesthesia In the holding area, after history taking and clinical examination, baseline vital signs will be recorded. After insertion of I.V. line all patients will be premedicated with ranitidine (50 mg) and paracetamol (1 gm). Standard monitoring will be maintained throughout; including electrocardiogram, blood pressure, respiratory rate, end-tidal CO2 and isoflurane levels, pulse oximetry, bispectral Index and temperature. Subjects will be preoxygenated with 100% O2 via a face mask and then given fentanyl 1.5 mic/kg and a sleeping dose of propofol to induce anesthesia. Cis-atracurium 0.15 mg/kg will be used to facilitate endotracheal intubation and mechanical ventilation followed by 0.03 mg/kg guided by TOF monitor while avoiding top up doses within the last 20 minutes of the surgical procedure. Anesthesia will be maintained by isoflurane 1.2 MAC in air:oxygen (50:50%) targeting BIS 40-50 all through the intraoperative course. Fentanyl 1 mic/kg will be given IV every 30 minutes intraoperatively. The study drug will be prepared by an anesthesia resident who is not involved in the study or care of the patient. All preventive measures against hypothermia will be done. Towards the end of surgery, ketorolac tromethamine (30 mg) will be slowly infused intravenously. At 10 min before the end of surgery, patients will receive an infusion during 10 min of either saline (control) or caffeine. The end of surgery is defined as time point zero (T0) for both groups and it corresponds to switching off isoflurane with the last skin stitch and marked the onset of the emergence time measurements. Towards the end of surgery, granisetron 1 mg will be slowly infused. After discontinuation of isoflurane, muscle relaxants will be reversed, and the subjects will be allowed to breathe spontaneously and emerge naturally until they opened their eyes. At this time, after the subjects open their eyes, they will be able to follow a command to open their mouths for the removal of endotracheal tubes. 35
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
normotensive patients aged 18-60 years (ASA physical status I or II, BMI 18-35 Kg/m2) scheduled for elective day case surgeries under general anaesthesia • Pregnant patients, • Breastfeeding • Severe visual or auditory impairment • Mental disorders or cognitive dysfunction. • Cardiac, liver, neuromuscular, endocrine or kidney diseases, • abnormal electrocardiogram findings • Peptic ulcer disease, gastroesophageal reflux disease or malabsorption diseases. • Severe anxiety. • History of epilepsy, antipsychotic, antidepressant medications or any other neurological problem. • Sensitivity to caffeine. • Use of caffeine and other caffeine containing tablets or beverages or methyl xanthines within 2 days prior to the study. • Cigarette smokers and alcohol and/or drug abusers. Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 60 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 03/05/2020 faculty of medicine menoufia university egypt
Ethics Committee Address
Street address City Postal code Country
25 yassin abdelghaffar street shebin elkom 32511 Egypt
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome the elapsed time after T0 until opening the eyes either spontaneously or upon verbal request repeated every 60 seconds by a blinded investigator. after T0
Secondary Outcome • The ET isoflurane, BIS level and minute volume will be observed continuously starting with isoflurane switching off till extubation. The last values before extubation will be recorded. from isoflurane dial swich off till extubation
Secondary Outcome • Mean arterial pressure, and heart rate before starting the study drug, every 3 minutes during the study drug administration, every 5 minutes after finishing the study drug for 1 hour in PACU.
Secondary Outcome • extubation time the time from the discontinuation of anesthesia till extubation.
Secondary Outcome • The elapsed time from T0 to the time the patient stated his/her full name (commands will be given every 20 s by a blinded investigator). from T0 to the time the patient stated his/her full name.
Secondary Outcome Adverse events: the occurrence of pain, nausea and/or vomiting, shivering, seizures, agitation, and any other adverse event. The visual analog scale (VAS), grading 0 to 10 cm, will be used to evaluate pain (0 = no pain to 10= the most pain I have ever felt) and nausea (0 = no nausea to 10 = as nauseous as I have ever been) during recovery. Pain requiring rescue medications (VAS>4) will be recorded. Agitation will be screened by modified Richmond sedation score during the first 3 postoperative hours starting from the extubation
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
anaesthesia department faculty of medicine menoufia university egypt 25 yassin abdelghaffar street shebin elkom 32511 Egypt
FUNDING SOURCES
Name of source Street address City Postal code Country
Authors 25 yassin abdelghaffar st Shebin elkom Menoufia 32511 Egypt
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Secondary Sponsor faculty of medicine menoufia university egypt 25 yassin abdelghaffar street shebin elkom 32511 Egypt University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator sabry abdallah sabryabdallah222@yahoo.com 00201204332202 25 yassin abdelghaffar street
City Postal code Country Position/Affiliation
shebin elkom 32511 Egypt lecturer of anaesthesia
Role Name Email Phone Street address
Public Enquiries khaled gaballah khgaballah@gmail.com 00201016009073 25 yassin abdelghaffar street
City Postal code Country Position/Affiliation
shebin elkom 32511 Egypt lecturer of anesthesia
Role Name Email Phone Street address
Scientific Enquiries sabry abdallah sabryabdallah222@yahoo.com 00201204332202 25 yassin abdelghaffar street
City Postal code Country Position/Affiliation
shebin elkom 32511 Egypt lecturer of anesthesia
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes All individual participant data collected during the trial, after deidentification will be available. Informed Consent Form,Statistical Analysis Plan,Study Protocol Immediately following publication, No end date Investigators whose proposed use of the data has been approved by an independent review committee (“learned intermediary”) identified for this purpose
URL Results Available Results Summary Result Posting Date First Journal Publication Date
Proposal should be directed to khgaballah@gmail.com. To gain access, data requestors will need to sign a data access agreement. No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information