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Trial registered on ANZCTR


Registration number
ACTRN12610000316000
Ethics application status
Approved
Date submitted
15/04/2010
Date registered
20/04/2010
Date last updated
11/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Hydromorphone as an adjuvant induction agent in reducing rocuronium induced pain and hemodynamic changes during tracheal intubation
Scientific title
Comparison of pretreatment with hydromorphone and fentanyl as an adjuvant induction agent in adult Korean surgical patients: the effect on rocuronium induced pain and hemodynamic change during tracheal intubation
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
rocuronium induced pain 257186 0
hemodynamic stability during induction 257215 0
nil 257218 0
Condition category
Condition code
Anaesthesiology 257322 257322 0 0
Anaesthetics

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Groups are divided according to the pretreatment drugs : (a)hydromorphone (hydromorphone group), (b) fentanyl (fentanyl group) or (c) normal saline (normal saline group)

During preoxygenation with 100% oxygen, the study drug was injected over 30 sec and an investigator blinded to the study drug observed the signs of side effects, such as apnea or coughing, for 30 sec. The study drugs were 5 ml of either intravenous (IV) hydromorphone hydrochloride 2 mg (Dilid registered trademark, Ha Na Phram, Seoul, Korea; hydromorphone group, n = 65) or intravenous (IV) fentanyl citrate 100 microgram (Gu Ju Pharm, Seoul, Korea; fentanyl group, n = 67) or intravenous (IV) normal saline (sodium chloride, Joong Wae Pharm, Seoul, Korea; saline group, n = 62).Then 2.5% thiopental sodium 5 mg/kg was injected over 5 sec. After the loss of consciousness and eyelash reflexes, when the appropriate end tidal carbon dioxide curve appeared on capnography upon trial of mask ventilation with the fraction of oxygen ratio (FiO2) 1.0, rocuronium 0.6 mg/kg was injected over 5 sec. The time interval between the study drug injection and rocuronium injection was set to be < 90 sec in all patients. Two anesthesiologists, one who administered the study drug and another to conduct the anesthetic induction, assessed the patient response during and immediately after rocuronium injection in a double-blinded manner. The two investigators were educated beforehand to grade the patient response according to the scale proposed by Shevchenko and colleagues 12: 1 = no movement, 2 = movement at the wrist only, 3 = movement/withdrawal involving the arm only (elbow/shoulder), 4 = generalized response, withdrawal or movement in more than one extremity.
Sevoflurane was started after the rocuronium injection and was adjusted to maintain an end-tidal concentration of 2.5-3.0 vol% in 100% oxygen. Two minutes after the rocuronium injection, the anesthesiologist who had more than 4 years’ experience of anesthetic practice performed tracheal intubation and applied controlled ventilation in order to maintain normocarbia without ballooning the cuff for 1 min to avoid stimulation. The patient movement and the status of vocal cord relaxation were observed during tracheal intubation. Anaesthesia was maintained with sevoflurane (end-tidal concentration of 2-3 vol%). The time interval between the study drug injection and intubation was designed to be within three to four minutes in all patients. The intubation time, which was defined as the time from mouth opening to obtaining the appropriate capnographic trace, was measured in all patients. The mean arterial pressure and heart rate were measured upon arrival at the operating room, 1 min before and after tracheal intubation. If there was an increase of heart rate (> 40% in baseline) and/or increased blood pressure with ST change in electrocardiogram after intubation, the administration of IV esmolol (0.3 mg/kg) was available.
Intervention code [1] 256338 0
Treatment: Drugs
Comparator / control treatment
Compared with fentanyl pretreatment or normal saline pretreatment
Control group
Active

Outcomes
Primary outcome [1] 258268 0
Reduction in rocuronium induced withdrawal movement. The two investigators were educated beforehand to grade the patient response according to the scale proposed by Shevchenko and colleagues 12: 1 = no movement, 2 = movement at the wrist only, 3 = movement/withdrawal involving the arm only (elbow/shoulder), 4 = generalized response, withdrawal or movement in more than one extremity.
Timepoint [1] 258268 0
Thirty seconds after administering the study drug, anesthesia was induced with 2.5% thiopental sodium 5 mg/kg. After the loss of consciousness, rocuronium 0.6 mg/kg was injected, and immediate withdrawal movements were recorded.
Secondary outcome [1] 263930 0
attenuation of hemodynamic profile (Mean arterial pressure, MAP. Heart rate, HR) during tracheal intubation
Timepoint [1] 263930 0
Two minutes after rocuronium injection, the tracheal intubation was performed and the hemodynamic changes were observed. The mean arterial pressure (MAP) and heart rate (HR) were measured upon arrival at the operating room, 1 min before and after tracheal intubation. The MAPs were measured by noninvasive blood pressure manometer and HRs were measured by using electrocardiograms.

Eligibility
Key inclusion criteria
Ages between 20-70 yr, American Society of Anesthesia (ASA) physical status I or II and undergoing general anesthesia for elective gastric and colorectal surgery from August 2008 to January 2009
Minimum age
20 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Known allergy to opioids, diabetes mellitus, asthma, neurological deficit, pregnancy or patients who had received analgesics or sedatives within the previous 24 h

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Enrollment is decided and permission of the patient is obtained by two of the anesthesiologists during preoperative roundings and allocation of the patients is facilitated by using a computer generated random numbers concealed in an envelope until one of two anesthesiologists (Sook Young Lee and Woo Seok Sim) unsealed the envelope and prepared the drug syringes accordingly.
The drug syringes are handed over to anesthesiologists blinded to the patient allocation to carry out the induction of anesthesia.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer generated random numbers was used to generate the sequence order.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 2588 0
Korea, Republic Of
State/province [1] 2588 0

Funding & Sponsors
Funding source category [1] 256843 0
Self funded/Unfunded
Name [1] 256843 0
Chul Joong Lee, M.D., Ph.D.
Address [1] 256843 0
Department of Anesthesiology and Pain Medicine, Samsung Seoul Hospital, Samsung Medical Center, Sungkyunkwan University School of Medicine,
#50 Ilwon-Dong, Kangnam-Gu, Seoul 135-710, Republic of Korea
Country [1] 256843 0
Primary sponsor type
Individual
Name
Chul Joong Lee, M.D., Ph.D.
Address
Department of Anesthesiology and Pain Medicine, Samsung Seoul Hospital, Samsung Medical Center, Sungkyunkwan University School of Medicine,
#50 Ilwon-Dong, Kangnam-Gu, Seoul 135-710, Republic of Korea
Country
Korea, Republic Of
Secondary sponsor category [1] 256119 0
Individual
Name [1] 256119 0
Sang Hyun Lee, M.D.
Address [1] 256119 0
Department of Anesthesiology and Pain Medicine, Samsung Seoul Hospital, Samsung Medical Center, Sungkyunkwan University School of Medicine,
#50 Ilwon-Dong, Kangnam-Gu, Seoul 135-710, Republic of Korea
Country [1] 256119 0
Korea, Republic Of

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258841 0
Samsung Medical Center Institutional Review Board
Ethics committee address [1] 258841 0
Samsung Seoul Hospital, Samsung Medical Center, Sungkyunkwan University School of Medicine,
#50 Ilwon-Dong, Kangnam-Gu, Seoul 135-710, Republic of Korea
Ethics committee country [1] 258841 0
Korea, Republic Of
Date submitted for ethics approval [1] 258841 0
27/06/2008
Approval date [1] 258841 0
29/07/2008
Ethics approval number [1] 258841 0
2008-06-051

Summary
Brief summary
Attenuation of rocuronium-induced withdrawal movements with opioids pretreatment may be attributed to peripheral anti-nociception at the veins. Hydromorphone, known to have a delayed systemic analgesic onset time of five minutes, may present immediate analgesia to rocuronium injection pain via peripheral effects. We compared the effects of a pretreatment with hydromorphone in reducing rocuronium-induced withdrawal movements and hemodynamic changes during tracheal intubation to those of fentanyl and normal saline. One hundred and ninety four patients were randomly assigned to receive 5 ml of hydromorphone 2 mg or fentanyl 100 µg or normal saline. Thirty seconds after administering the study drug, anaesthesia was induced with 2.5% thiopental sodium 5 mg/kg. After the loss of consciousness, rocuronium 0.6 mg/kg was injected, and immediate withdrawal movements were recorded. Two minutes after rocuronium injection, the tracheal intubation was performed and the hemodynamic changes were observed. A total of 190 patients were analyzed and the overall incidence of withdrawal movements was significantly lower in the hydromorphone (2 patients; 3%) and fentanyl group (5 patients; 7.9%) than in saline group (36 patients; 59%) (P < 0.001). The MAP (mean arterial pressure) and HR (heart rate) after intubation in hydromorphone and fentanyl group were significantly lower than those in saline group (fentanyl group P = 0.003, < 0.001; hydromorphone group P < 0.001, < 0.001 respectively). Hydromorphone conveyed immediate substantial analgesia to rocuronium pain-induced withdrawal movement comparable to fentanyl effect and also reduced the hemodynamic responses to tracheal intubation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31058 0
Address 31058 0
Country 31058 0
Phone 31058 0
Fax 31058 0
Email 31058 0
Contact person for public queries
Name 14305 0
Chul Joong Lee, M.D., Ph.D.
Address 14305 0
Department of Anesthesiology and Pain Medicine, Samsung Seoul Hospital, Samsung Medical Center, Sungkyunkwan University School of Medicine,
#50 Ilwon-Dong, Kangnam-Gu, Seoul 135-710, Republic of Korea
Country 14305 0
Korea, Republic Of
Phone 14305 0
+82-2-3410-2470
Fax 14305 0
Email 14305 0
chuljlee@skku.edu
Contact person for scientific queries
Name 5233 0
Chul Joong Lee, M.D., Ph.D.
Address 5233 0
Department of Anesthesiology and Pain Medicine, Samsung Seoul Hospital, Samsung Medical Center, Sungkyunkwan University School of Medicine,
#50 Ilwon-Dong, Kangnam-Gu, Seoul 135-710, Republic of Korea
Country 5233 0
Korea, Republic Of
Phone 5233 0
+82-2-3410-2470
Fax 5233 0
Email 5233 0
chuljlee@skku.edu

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary