Bariatric Surgery Candidate, Glucose Intolerance, Insulin Resistance
Conditions
Keywords
Impaired Glucose Tolerance, Obese patients, Dexmedetomidine
Brief summary
This study investigated the effect of dexmedetomidine in obese patients undergoing bariatric surgery.
Detailed description
A prospective, double-blind, randomized controlled trial was performed. Consenting obese adult patients with impaired glucose tolerance, undergoing bariatric surgery, were randomized, by a computer, to receive placebo (0.9% Sodium-chloride) or dexmedetomidine 1 ug/kg bolus in 10 minutes followed by an infusion of 0.5 ug/kg/h until the end of surgery. Baseline HgbA1c, glucose, and insulin plasmatic levels were measured. Subsequently, glucose and insulin levels were taken every 2 hours during the first 12 hours from the onset of the drug infusion. Intraoperative fentanyl and postoperative morphine consumption, pain score, the occurrence of emesis, and postoperative sedation levels were recorded as secondary outcomes.
Interventions
DRUGDexmedetomidine
A bolus of 1ug/kg in 10 minutes, followed by an infusion of 0.5ug/kg/h until the end of surgery.
The same infusion rate used in the dexmedetomidine group.
DRUGFentanyl
Intraoperative fentanyl was given in case of 25% increment in the blood pressure and/or heart rate in comparison to baseline (previous anesthesia induction).
DRUGMorphine Sulfate
Boluses of 3mg of intravenous morphine were given in the postoperative acute care unit. Once the pain score was equal or less than 3/10 the patient-controlled analgesia pumps were installed and the patients were discharged to their room.
Sponsors
Pontificia Universidad Catolica de Chile
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Blinded
Intervention model description
Prospective, randomized, placebo-controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Obese patient (BMI\>30) * American Society of Anesthesiologists grades II or III * Diagnosis of impaired glucose tolerance * Undergoing sleeve gastrectomy
Exclusion criteria
* Baseline glucose \> 200mg/dl * Diagnosis of Diabetes * Under corticosteroids treatment * Oral hypoglycemic medication within 7 days previous surgery * Use of insulin within 24h previous surgery * Allergy to any drug used in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasmatic Glucose Levels (mg/dl). | Baseline levels(T0) and at hour 2(T1), 4(T2), 6(T3), 8(T4), 10(T5), and 12(T6) after the onset of bolus and infusion of dexmedetomidine | Change of baseline glucose levels within the first 12 postoperative hours. |
| Plasmatic Insulin Levels (uU/ml). | Baseline levels(T0) and at hour 2(T1), 4(T2), 6(T3), 8(T4), 10(T5), and 12(T6) after the onset of bolus and infusion of dexmedetomidine | Change of baseline insulin levels within the first 12 postoperative hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Scores in the First 24 Postoperative Hours. | At postoperative hours 2(T1), 4(T2), 6(T3), 8(T4), 10(T5), 12(T6) and 24(T7). | Visual analogue scale (VAS), provided by patients, ranging from 0 to 10 (0= no pain and 10= worst possible pain). We considered a pain score between 1-3, 4-6 and 7-10 as mild, moderate and severe pain, respectively. |
| Fentanyl Consumption. | Since the beginning of anesthesia until the end of it, an average of one hour and a half. | Amount of fentanyl (ug/kg) intraoperatively administered. |
| Postoperative Nausea and Vomiting. | Postoperative nausea and vomiting during the first 12 postoperative hours. | Number of patients with postoperative nausea and vomiting in the first 12 postoperative hours. |
| Sedation-agitation Scores in the First 12 Postoperative Hours. | At postoperative hours 2(T1), 4(T2), 6(T3), 8(T4), 10(T5) and 12(T6). | Sedation-agitation scale (SAS), ranging from 1 to 7 (1=unarousable, 2=very sedated, 3=sedated, 4=calm and cooperative, 5=agitated, 6=very agitated and 7=dangerous agitation). |
| Amount (mg) of Morphine Consumed. | At 24h postoperative hours. | Morphine consumption in the first 24 postoperative hours. |
Participant flow
Recruitment details
The patients were recruited at the Pontifical Catholic University Hospital between 2012 and 2013. Twenty patients were assigned to each arm to allow some dropouts. Nonetheless, every randomized patient included in the study was analyzed at the end of it (intention to treat analysis).
Pre-assignment details
No patient was excluded from the study after being assigned to one arm/group.
Participants by arm
| Arm | Count |
|---|---|
| Dexmedetomidine After anesthesia induction, patients who were randomized to the Dexmedetomidine group, received a bolus of 1ug/kg in 10 minutes, followed by an infusion of 0.5ug/kg/h until the end of surgery. In the case of intraoperative increment of the blood pressure and/or heart rate more than 25% from its baseline, fentanyl 1ug/kg was administered.
Dexmedetomidine: A bolus of 1ug/kg in 10 minutes, followed by an infusion of 0.5ug/kg/h until the end of surgery.
Fentanyl: Intraoperative fentanyl was given in the case of 25% increment in the blood pressure and/or heart rate in comparison to baseline (previous anesthesia induction).
Morphine Sulfate: Boluses of 3mg of intravenous morphine were given in the postoperative acute care unit. Once the pain score was equal or less than 3/10 a patient-controlled analgesia pump was installed and the patient was discharged to his/her room. | 20 |
| 0.9% Sodium-chloride After anesthesia induction, patients who were randomized to the Placebo group received a bolus and infusion of 0.9% normal saline at the same rate as the Dexmedetomidine group until the end of surgery. In the case of intraoperative increment of the blood pressure and/or heart rate more than 25% from its baseline, fentanyl 1ug/kg was administered.
0.9% Sodium-chloride: The same dose used in the dexmedetomidine group (bolus and infusion).
Fentanyl: Intraoperative fentanyl was given in the case of 25% increment in the blood pressure and/or heart rate in comparison to baseline (previous anesthesia induction).
Morphine Sulfate: Boluses of 3mg of intravenous morphine were given in the postoperative acute care unit. Once the pain score was equal or less than 3/10 a patient-controlled analgesia pump was installed and the patient was discharged to his/her room. | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Dexmedetomidine | 0.9% Sodium-chloride | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 20 Participants | 40 Participants |
| Age, Continuous | 33 years STANDARD_DEVIATION 10.2 | 31.5 years STANDARD_DEVIATION 9.9 | 32 years STANDARD_DEVIATION 10 |
| ASA physical status II | 20 Participants | 20 Participants | 40 Participants |
| Baseline HbA1c | 5.4 Percentage STANDARD_DEVIATION 0.2 | 5.4 Percentage STANDARD_DEVIATION 0.4 | 5.4 Percentage STANDARD_DEVIATION 0.3 |
| Body Mass Index (BMI) | 34.4 kg/m^2 STANDARD_DEVIATION 2.5 | 35.2 kg/m^2 STANDARD_DEVIATION 3.6 | 34.8 kg/m^2 STANDARD_DEVIATION 3.1 |
| Region of Enrollment Chile | 20 participants | 20 participants | 40 participants |
| Risk score for postoperative nausea and vomiting (PONV) in adults 0 risk factor | 0 Participants | 0 Participants | 0 Participants |
| Risk score for postoperative nausea and vomiting (PONV) in adults 1 risk factor | 0 Participants | 4 Participants | 4 Participants |
| Risk score for postoperative nausea and vomiting (PONV) in adults 2 risk factors | 14 Participants | 9 Participants | 23 Participants |
| Risk score for postoperative nausea and vomiting (PONV) in adults 3 risk factors | 5 Participants | 6 Participants | 11 Participants |
| Risk score for postoperative nausea and vomiting (PONV) in adults 4 risk factors | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 20 Participants | 15 Participants | 35 Participants |
| Sex: Female, Male Male | 0 Participants | 5 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 17 / 20 | 10 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Plasmatic Glucose Levels (mg/dl).
Change of baseline glucose levels within the first 12 postoperative hours.
Time frame: Baseline levels(T0) and at hour 2(T1), 4(T2), 6(T3), 8(T4), 10(T5), and 12(T6) after the onset of bolus and infusion of dexmedetomidine
Population: All recruited population was analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexmedetomidine | Plasmatic Glucose Levels (mg/dl). | Hour 10 (T5) | 130 mg/dl | Standard Deviation 62 |
| Dexmedetomidine | Plasmatic Glucose Levels (mg/dl). | Hour 12 (T6) | 125 mg/dl | Standard Deviation 31 |
| Dexmedetomidine | Plasmatic Glucose Levels (mg/dl). | Hour 2 (T1) | 114 mg/dl | Standard Deviation 29 |
| Dexmedetomidine | Plasmatic Glucose Levels (mg/dl). | Hour 4 (T2) | 124 mg/dl | Standard Deviation 25 |
| Dexmedetomidine | Plasmatic Glucose Levels (mg/dl). | Hour 6 (T3) | 131 mg/dl | Standard Deviation 60 |
| Dexmedetomidine | Plasmatic Glucose Levels (mg/dl). | Hour 8 (T4) | 122 mg/dl | Standard Deviation 41 |
| Dexmedetomidine | Plasmatic Glucose Levels (mg/dl). | Baseline level (T0) | 80 mg/dl | Standard Deviation 15 |
| 0.9% Sodium-chloride | Plasmatic Glucose Levels (mg/dl). | Hour 6 (T3) | 120 mg/dl | Standard Deviation 16 |
| 0.9% Sodium-chloride | Plasmatic Glucose Levels (mg/dl). | Hour 10 (T5) | 117 mg/dl | Standard Deviation 18 |
| 0.9% Sodium-chloride | Plasmatic Glucose Levels (mg/dl). | Hour 4 (T2) | 129 mg/dl | Standard Deviation 17 |
| 0.9% Sodium-chloride | Plasmatic Glucose Levels (mg/dl). | Hour 12 (T6) | 117 mg/dl | Standard Deviation 17 |
| 0.9% Sodium-chloride | Plasmatic Glucose Levels (mg/dl). | Baseline level (T0) | 82 mg/dl | Standard Deviation 8 |
| 0.9% Sodium-chloride | Plasmatic Glucose Levels (mg/dl). | Hour 8 (T4) | 118 mg/dl | Standard Deviation 17 |
| 0.9% Sodium-chloride | Plasmatic Glucose Levels (mg/dl). | Hour 2 (T1) | 111 mg/dl | Standard Deviation 20 |
Comparison: Null hypothesis: There is no difference in plasmatic glucose levels between dexmedetomidine and 0.9% sodium-chloride groups.p-value: 0.38Mixed Models Analysis
Primary
Plasmatic Insulin Levels (uU/ml).
Change of baseline insulin levels within the first 12 postoperative hours.
Time frame: Baseline levels(T0) and at hour 2(T1), 4(T2), 6(T3), 8(T4), 10(T5), and 12(T6) after the onset of bolus and infusion of dexmedetomidine
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexmedetomidine | Plasmatic Insulin Levels (uU/ml). | Baseline level (T0) | 10.5 uU/dl | Standard Deviation 6 |
| Dexmedetomidine | Plasmatic Insulin Levels (uU/ml). | Hour 8 (T4) | 16.6 uU/dl | Standard Deviation 8.9 |
| Dexmedetomidine | Plasmatic Insulin Levels (uU/ml). | Hour 10 (T5) | 16 uU/dl | Standard Deviation 10 |
| Dexmedetomidine | Plasmatic Insulin Levels (uU/ml). | Hour 2 (T1) | 11.8 uU/dl | Standard Deviation 9 |
| Dexmedetomidine | Plasmatic Insulin Levels (uU/ml). | Hour 4 (T2) | 16.7 uU/dl | Standard Deviation 9.5 |
| Dexmedetomidine | Plasmatic Insulin Levels (uU/ml). | Hour 6 (T3) | 16.8 uU/dl | Standard Deviation 11.4 |
| Dexmedetomidine | Plasmatic Insulin Levels (uU/ml). | Hour 12 (T6) | 16.6 uU/dl | Standard Deviation 9.2 |
| 0.9% Sodium-chloride | Plasmatic Insulin Levels (uU/ml). | Hour 10 (T5) | 24 uU/dl | Standard Deviation 17.7 |
| 0.9% Sodium-chloride | Plasmatic Insulin Levels (uU/ml). | Hour 4 (T2) | 30.3 uU/dl | Standard Deviation 19.9 |
| 0.9% Sodium-chloride | Plasmatic Insulin Levels (uU/ml). | Hour 8 (T4) | 21.5 uU/dl | Standard Deviation 10.4 |
| 0.9% Sodium-chloride | Plasmatic Insulin Levels (uU/ml). | Hour 12 (T6) | 25.9 uU/dl | Standard Deviation 18.3 |
| 0.9% Sodium-chloride | Plasmatic Insulin Levels (uU/ml). | Baseline level (T0) | 11.2 uU/dl | Standard Deviation 6 |
| 0.9% Sodium-chloride | Plasmatic Insulin Levels (uU/ml). | Hour 6 (T3) | 23 uU/dl | Standard Deviation 11.4 |
| 0.9% Sodium-chloride | Plasmatic Insulin Levels (uU/ml). | Hour 2 (T1) | 19.9 uU/dl | Standard Deviation 11.8 |
Comparison: Null hypothesis: There is no difference in insulin levels between dexmedetomidine and 0.9% sodium-chloride groups.p-value: 0.02Mixed Models Analysis
Secondary
Amount (mg) of Morphine Consumed.
Morphine consumption in the first 24 postoperative hours.
Time frame: At 24h postoperative hours.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexmedetomidine | Amount (mg) of Morphine Consumed. | 26 mg | Standard Deviation 14.4 |
| 0.9% Sodium-chloride | Amount (mg) of Morphine Consumed. | 18.4 mg | Standard Deviation 10.6 |
Secondary
Fentanyl Consumption.
Amount of fentanyl (ug/kg) intraoperatively administered.
Time frame: Since the beginning of anesthesia until the end of it, an average of one hour and a half.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexmedetomidine | Fentanyl Consumption. | 6.0 mcg/kg | Standard Deviation 2.2 |
| 0.9% Sodium-chloride | Fentanyl Consumption. | 7 mcg/kg | Standard Deviation 2.4 |
Secondary
Pain Scores in the First 24 Postoperative Hours.
Visual analogue scale (VAS), provided by patients, ranging from 0 to 10 (0= no pain and 10= worst possible pain). We considered a pain score between 1-3, 4-6 and 7-10 as mild, moderate and severe pain, respectively.
Time frame: At postoperative hours 2(T1), 4(T2), 6(T3), 8(T4), 10(T5), 12(T6) and 24(T7).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dexmedetomidine | Pain Scores in the First 24 Postoperative Hours. | Hour 2 (T1) Pain at rest | 0 units on a scale |
| Dexmedetomidine | Pain Scores in the First 24 Postoperative Hours. | Hour 2 (T1) Pain at movement | 0 units on a scale |
| Dexmedetomidine | Pain Scores in the First 24 Postoperative Hours. | Hour 4 (T2) Pain at rest | 4 units on a scale |
| Dexmedetomidine | Pain Scores in the First 24 Postoperative Hours. | Hour 4 (T2) Pain at movement | 5 units on a scale |
| Dexmedetomidine | Pain Scores in the First 24 Postoperative Hours. | Hour 6 (T3) Pain at rest | 3 units on a scale |
| Dexmedetomidine | Pain Scores in the First 24 Postoperative Hours. | Hour 6 (T3) Pain at movement | 4 units on a scale |
| Dexmedetomidine | Pain Scores in the First 24 Postoperative Hours. | Hour 8 (T4) Pain at rest | 3 units on a scale |
| Dexmedetomidine | Pain Scores in the First 24 Postoperative Hours. | Hour 8 (T4) Pain at movement | 4 units on a scale |
| Dexmedetomidine | Pain Scores in the First 24 Postoperative Hours. | Hour 10 (T5) Pain at rest | 3 units on a scale |
| Dexmedetomidine | Pain Scores in the First 24 Postoperative Hours. | Hour 10 (T5) Pain at movement | 5 units on a scale |
| Dexmedetomidine | Pain Scores in the First 24 Postoperative Hours. | Hour 12 (T6) Pain at rest | 3 units on a scale |
| Dexmedetomidine | Pain Scores in the First 24 Postoperative Hours. | Hour 12 (T6) Pain at movement | 3 units on a scale |
| Dexmedetomidine | Pain Scores in the First 24 Postoperative Hours. | Hour 24 (T7) Pain at rest | 2 units on a scale |
| Dexmedetomidine | Pain Scores in the First 24 Postoperative Hours. | Hour 24 (T7) Pain at movement | 3 units on a scale |
| 0.9% Sodium-chloride | Pain Scores in the First 24 Postoperative Hours. | Hour 12 (T6) Pain at rest | 1 units on a scale |
| 0.9% Sodium-chloride | Pain Scores in the First 24 Postoperative Hours. | Hour 2 (T1) Pain at rest | 0 units on a scale |
| 0.9% Sodium-chloride | Pain Scores in the First 24 Postoperative Hours. | Hour 8 (T4) Pain at movement | 4 units on a scale |
| 0.9% Sodium-chloride | Pain Scores in the First 24 Postoperative Hours. | Hour 2 (T1) Pain at movement | 0 units on a scale |
| 0.9% Sodium-chloride | Pain Scores in the First 24 Postoperative Hours. | Hour 24 (T7) Pain at rest | 0 units on a scale |
| 0.9% Sodium-chloride | Pain Scores in the First 24 Postoperative Hours. | Hour 4 (T2) Pain at rest | 3 units on a scale |
| 0.9% Sodium-chloride | Pain Scores in the First 24 Postoperative Hours. | Hour 10 (T5) Pain at rest | 1 units on a scale |
| 0.9% Sodium-chloride | Pain Scores in the First 24 Postoperative Hours. | Hour 4 (T2) Pain at movement | 4 units on a scale |
| 0.9% Sodium-chloride | Pain Scores in the First 24 Postoperative Hours. | Hour 12 (T6) Pain at movement | 3 units on a scale |
| 0.9% Sodium-chloride | Pain Scores in the First 24 Postoperative Hours. | Hour 6 (T3) Pain at rest | 2 units on a scale |
| 0.9% Sodium-chloride | Pain Scores in the First 24 Postoperative Hours. | Hour 10 (T5) Pain at movement | 3 units on a scale |
| 0.9% Sodium-chloride | Pain Scores in the First 24 Postoperative Hours. | Hour 6 (T3) Pain at movement | 4 units on a scale |
| 0.9% Sodium-chloride | Pain Scores in the First 24 Postoperative Hours. | Hour 24 (T7) Pain at movement | 3 units on a scale |
| 0.9% Sodium-chloride | Pain Scores in the First 24 Postoperative Hours. | Hour 8 (T4) Pain at rest | 1 units on a scale |
Secondary
Postoperative Nausea and Vomiting.
Number of patients with postoperative nausea and vomiting in the first 12 postoperative hours.
Time frame: Postoperative nausea and vomiting during the first 12 postoperative hours.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexmedetomidine | Postoperative Nausea and Vomiting. | 16 Participants |
| 0.9% Sodium-chloride | Postoperative Nausea and Vomiting. | 19 Participants |
Secondary
Sedation-agitation Scores in the First 12 Postoperative Hours.
Sedation-agitation scale (SAS), ranging from 1 to 7 (1=unarousable, 2=very sedated, 3=sedated, 4=calm and cooperative, 5=agitated, 6=very agitated and 7=dangerous agitation).
Time frame: At postoperative hours 2(T1), 4(T2), 6(T3), 8(T4), 10(T5) and 12(T6).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dexmedetomidine | Sedation-agitation Scores in the First 12 Postoperative Hours. | Hour 2 (T1) | 3 score on a scale |
| Dexmedetomidine | Sedation-agitation Scores in the First 12 Postoperative Hours. | Hour 4 (T2) | 4 score on a scale |
| Dexmedetomidine | Sedation-agitation Scores in the First 12 Postoperative Hours. | Hour 6 (T3) | 4 score on a scale |
| Dexmedetomidine | Sedation-agitation Scores in the First 12 Postoperative Hours. | Hour 8 (T4) | 4 score on a scale |
| Dexmedetomidine | Sedation-agitation Scores in the First 12 Postoperative Hours. | Hour 10 (T5) | 4 score on a scale |
| Dexmedetomidine | Sedation-agitation Scores in the First 12 Postoperative Hours. | Hour 12 (T6) | 4 score on a scale |
| 0.9% Sodium-chloride | Sedation-agitation Scores in the First 12 Postoperative Hours. | Hour 10 (T5) | 4 score on a scale |
| 0.9% Sodium-chloride | Sedation-agitation Scores in the First 12 Postoperative Hours. | Hour 2 (T1) | 4 score on a scale |
| 0.9% Sodium-chloride | Sedation-agitation Scores in the First 12 Postoperative Hours. | Hour 8 (T4) | 4 score on a scale |
| 0.9% Sodium-chloride | Sedation-agitation Scores in the First 12 Postoperative Hours. | Hour 4 (T2) | 4 score on a scale |
| 0.9% Sodium-chloride | Sedation-agitation Scores in the First 12 Postoperative Hours. | Hour 12 (T6) | 4 score on a scale |
| 0.9% Sodium-chloride | Sedation-agitation Scores in the First 12 Postoperative Hours. | Hour 6 (T3) | 4 score on a scale |