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The investigators want to investigate the effect of low dose S+ ketamine compared to placebo on cumulative morphine consumption at 24 hours in 90 women undergoing open abdominal hysterectomy with remifentanil-propofol target controlled infusion (TCI) in KK Women's and Children's Hospital. The secondary aims are to investigate the use of low dose S+ ketamine on the incidence of nausea, vomiting, pruritus (opioid side effect), sedation score and psycho mimetic assessment compared to placebo group. The investigators propose to conduct a double blinded, randomized controlled study in women undergoing open abdominal hysterectomy with remifentanil-propofol TCI. (1) Treatment Group: intravenous ketamine 0.5 mg/kg at the beginning and 0.5 mg/kg 20 minutes before extubation. (2) Control Group: intravenous normal saline (as placebo) at the beginning and 20 minutes before extubation.
A number of 90 American Society of Anesthesiologists (ASA) I and II patients undergoing elective open abdominal hysterectomies will be randomly distributed in two groups of 45 patient's each and assigned to receive one of the of the following:
Randomization procedure is performed by the unblinded study team investigator. Patients will be randomized to either the treatment or control groups with a 1:1 allocation ratio. Sequence generation will be performed using a computerized random number generator, employing a permuted block randomization scheme. Allocation concealment will be maintained by having the random numbers pre-generated by an off-site statistician who will not be involved in subject recruitment. Implementation will be via serially numbered opaque sealed envelopes.
Throughout the study period, blinded study members will perform drug administration and data collection, while unblinded study members will be in charge for the investigational drug storage, dispensing and preparation. Any premature unblinding (e.g. accidental unblinding, unblinding due a serious adverse event) of the investigational product will be promptly documented and explained. In the case of adverse effect or severe adverse effect requiring information on the study treatment to manage a patient, the treatment code of the patient will be unblinded.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Esketamine | Active Comparator | Esketamine and remifentanil to be given alongside with propofol through target control infusion pump. |
|
| Control | Placebo Comparator | Saline and remifentanil to be given alongside with propofol through target control infusion pump. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Esketamine | Drug | intravenous S+ketamine 0.25 mg/kg (i.v. bolus) at the beginning and 0.25 mg/kg (i.v. bolus) 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Marsh model |
| Measure | Description | Time Frame |
|---|---|---|
| Post-operative Cumulative morphine consumption at 24 hours | Post-operative Cumulative morphine consumption at 24 hours will be measured in the S-ketamine group compared to the placebo group | 1 day |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of nausea | The use of low dose S-ketamine will reduce the incidence of nausea / vomiting, pruritus (opioid side effect) compared to placebo in women undergoing open abdominal hysterectomy with remifentanil-propofol target controlled infusion. | 1 day |
| Incidence of vomiting |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Farida Ithnin, MBBCh | KK Women's and Children's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kk Women'S and Children'S Hospital | Singapore | 229899 | Singapore |
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| ID | Term |
|---|---|
| C000629870 | Esketamine |
| D007649 | Ketamine |
| D012965 | Sodium Chloride |
| D000077208 | Remifentanil |
| D015742 | Propofol |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
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|
| Saline | Drug | intravenous normal saline (as placebo, with similar volume) at the beginning and 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Schnider model |
|
|
| Remifentanil | Drug | Either S+ketamine or saline at the beginning and 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Schnider model |
|
|
| Propofol | Drug | Either S+ketamine or saline at the beginning and 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Schnider model |
|
|
The use of low dose S-ketamine will reduce the incidence of nausea / vomiting, pruritus (opioid side effect) compared to placebo in women undergoing open abdominal hysterectomy with remifentanil-propofol target controlled infusion. |
| 1 day |
| Incidence of pruritus | The use of low dose S-ketamine will reduce the incidence of nausea / vomiting, pruritus (opioid side effect) compared to placebo in women undergoing open abdominal hysterectomy with remifentanil-propofol target controlled infusion. | 1 day |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| D011422 | Propionates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |