Propofol Adverse Reaction, Anesthesia
Conditions
Keywords
propofol synergy, fentanyl, anesthesia induction
Brief summary
Objective: Determine if, by reducing the dose of propofol and increasing the time elapsed between fentanyl and propofol administration, hemodynamic response is improved. Methods: Patients were randomized into time groups (2 and 1 minute) and each subdivided into dose groups (1, 1.5 and 2 mg kg-1) obtaining six time-dose groups. After receiving 2 μg kg-1 of fentanyl, propofol was administered after the predetermined time. Time to hypnosis (BIS\<60) and hemodynamic parameters at pre-induction, pre-intubation and postintubation were registered.
Detailed description
A minimum of 162 patients were required, considering an expected Mean Difference of 5 with expected Standard Deviation of 22, confidence level of 95% and power of 80%. Estimating a possible loss of 15%, it was raised to 192. Consecutive identification numbers were assigned and the sample was randomized in six groups of 32 patients according to time and dose of propofol. Pre-oxygenation was performed until the expired oxygen fraction exceeded 80% and 2 µg/kg of intravenous fentanyl were administered. Depending on the study group, 1 or 2 minutes were allowed to pass and 1, 1.5 or 2 mg/kg of propofol were supplied (prior administration of intravenous lidocaine 0.5 mg/kg). The time in which the BIS dropped below 60 was recorded. If it did not reach that level after two minutes or when it exceeded it but then rose above 60 again, an extra dose of propofol of 0.5 mg/kg was administered. Muscle relaxation was performed with rocuronium 0.6 mg/kg. The patient was manually ventilated until endotracheal intubation was performed by the same experienced anaesthesiologist and connected to mechanical ventilation. Data were collected manually. Statistical analysis was performed using SPSS ver. 22. Inferential statistics were performed using t-test for quantitative variables, chi-square for qualitative and ANOVA for qualitative and quantitative comparisons. Non-parametric statistical tests were used when necessary. Confidence intervals were estimated at a level of 95% and a P value of \<.05 was considered statistically significant.
Interventions
1, 1.5 or 2 mg/kg of propofol according to the subgroup
Sponsors
Hospital Central de la Defensa Gómez Ulla
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Subject)
Masking description
aleatory assignation, time measured by nurses, drugs administrated by principal investigator
Intervention model description
2 time groups, divided into 3 dose groups
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Adults who required general anesthesia * General anesthesia with endotracheal intubation (no supraglottic devices) * Signed informed consent * Non-cardiac surgery * Same anesthesiologist
Exclusion criteria
* Hemodynamic instability (systolic BP \< 90 mmHg with clinical signs of low cardiac output: impaired consciousness, diuresis \<0.5 ml/kg/h, central venous saturation \<60% with normal arterial saturation or lactate \>3 mmol/l) * Increased risk of bronchoaspiration (absence of fasting, stomach retention, intestinal obstruction, pregnancy, etc.) * Suspected difficult airway * Known allergy to anesthetic drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure Variation | Baseline before fentanyl administration, pre-intubation after propofol and bispectral index<60 and postintubation 15 seconds after endotracheal tube positioned | Non-invasive systolic blood pressure change (%) at baseline, pre-intubation and postintubation. Positive results mean percentage reduction in SBP between the studied moments. Negative results mean percentage increase in SBP between the studied moments. |
| Heart Rate Variation | Baseline before fentanyl administration, pre-intubation after propofol and bispectral index<60 and postintubation 15 seconds after endotracheal tube positioned | Heart rate change (%) registered at baseline, pre-intubation and postintubation. Positive results mean percentage reduction in HR between the studied moments. Negative results mean percentage increase in HR between the studied moments. |
| Systolic Blood Pressure Variation in Elderly (>55y) | Baseline before fentanyl administration, pre-intubation after propofol and bispectral index<60 and postintubation 15 seconds after endotracheal tube positioned | Non-invasive SBP change (%) in patients \> 55 years at baseline, pre-intubation and postintubation. Positive results mean percentage reduction in SBP between the studied moments. Negative results mean percentage increase in SBP between the studied moments. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Hypnosis | After administration of propofol, time is measured in seconds until BIS values are less than 60 | Bispectral index (BIS)\<60 meaning general anesthesia, BIS\>60 meaning mild/moderate sedation. We measure the time until patient reachs hypnosis |
| Number of Patients Who Needed Vasoactive Drug | 1 minute after intubation | Patients who suffered SPB reduction \> 30% or SPB \< 90mmHg, receive vasoactive drugs |
Countries
Spain
Participant flow
Recruitment details
Every patient who agreed to participate and required general anesthesia with endotracheal intubation by the same anesthesiologist
Pre-assignment details
Randomization was prior to data collection. The patient number was assigned by computerized randomizer to the 6 study groups. The collection was systematic from day one of the study, including all patients who met inclusion criteria and accepted participation. Of 192 patients enrolled, 186 met inclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| 2 Minute - 2 mg/kg Group 2 mcg/kg of fentanyl administrated intravenously. wait for 2 minutes to inject 2 mg/kg of propofol | 31 |
| 2 Minute - 1,5 mg/kg Group 2 mcg/kg of fentanyl administrated intravenously. wait for 2 minutes to inject 1,5 mg/kg of propofol | 30 |
| 2 Minute - 1 mg/kg Group 2 mcg/kg of fentanyl administrated intravenously. wait for 2 minutes to inject 1 mg/kg of propofol | 31 |
| 1 Minute - 2 mg/kg Group 2 mcg/kg of fentanyl administrated intravenously. wait for 1 minute to inject 2 mg/kg of propofol | 31 |
| 1 Minute - 1,5 mg/kg Group 2 mcg/kg of fentanyl administrated intravenously. wait for 1 minute to inject 1,5 mg/kg of propofol | 32 |
| 1 Minute - 1 mg/kg Group 2 mcg/kg of fentanyl administrated intravenously. wait for 1 minute to inject 1 mg/kg of propofol | 31 |
| Total | 186 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Monitorization problem | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 1 | 1 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | 2 Minute - 2 mg/kg Group | 2 Minute - 1,5 mg/kg Group | 2 Minute - 1 mg/kg Group | 1 Minute - 2 mg/kg Group | 1 Minute - 1,5 mg/kg Group | 1 Minute - 1 mg/kg Group | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 59 years STANDARD_DEVIATION 20 | 61 years STANDARD_DEVIATION 17 | 60 years STANDARD_DEVIATION 19 | 59 years STANDARD_DEVIATION 17 | 64 years STANDARD_DEVIATION 18 | 55 years STANDARD_DEVIATION 16 | 60 years STANDARD_DEVIATION 18 |
| anesthesia risk (ASA), categorical High risk | 11 Participants | 11 Participants | 14 Participants | 10 Participants | 19 Participants | 10 Participants | 75 Participants |
| anesthesia risk (ASA), categorical Low risk | 20 Participants | 19 Participants | 17 Participants | 21 Participants | 13 Participants | 21 Participants | 111 Participants |
| Antihypertensive treatment | 9 Participants | 9 Participants | 12 Participants | 10 Participants | 12 Participants | 11 Participants | 63 Participants |
| Heart rate treatment | 11 Participants | 7 Participants | 10 Participants | 9 Participants | 11 Participants | 3 Participants | 51 Participants |
| Hypertension | 15 Participants | 9 Participants | 15 Participants | 13 Participants | 16 Participants | 13 Participants | 81 Participants |
| Race and Ethnicity Not Collected | — | — | — | — | — | — | 0 Participants |
| Sex: Female, Male Female | 15 Participants | 14 Participants | 17 Participants | 17 Participants | 18 Participants | 14 Participants | 95 Participants |
| Sex: Female, Male Male | 16 Participants | 16 Participants | 14 Participants | 14 Participants | 14 Participants | 17 Participants | 91 Participants |
| weight | 73 kilograms STANDARD_DEVIATION 16 | 77 kilograms STANDARD_DEVIATION 17 | 70 kilograms STANDARD_DEVIATION 15 | 71 kilograms STANDARD_DEVIATION 15 | 71 kilograms STANDARD_DEVIATION 15 | 73 kilograms STANDARD_DEVIATION 15 | 72 kilograms STANDARD_DEVIATION 15 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 30 | 0 / 31 | 0 / 31 | 0 / 32 | 0 / 31 |
| other Total, other adverse events | 4 / 31 | 1 / 30 | 0 / 31 | 2 / 31 | 3 / 32 | 0 / 31 |
| serious Total, serious adverse events | 0 / 31 | 0 / 30 | 0 / 31 | 0 / 31 | 0 / 32 | 0 / 31 |
Outcome results
Primary
Heart Rate Variation
Heart rate change (%) registered at baseline, pre-intubation and postintubation. Positive results mean percentage reduction in HR between the studied moments. Negative results mean percentage increase in HR between the studied moments.
Time frame: Baseline before fentanyl administration, pre-intubation after propofol and bispectral index<60 and postintubation 15 seconds after endotracheal tube positioned
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 Minute - 2 mg/kg Group | Heart Rate Variation | HR baseline/postintubation | -10 percentage of variation | Standard Deviation 19 |
| 2 Minute - 2 mg/kg Group | Heart Rate Variation | HR baseline/pre-intubation | 6 percentage of variation | Standard Deviation 13 |
| 2 Minute - 2 mg/kg Group | Heart Rate Variation | HR pre-intubation/postintubation | -17 percentage of variation | Standard Deviation 19 |
| 2 Minute - 1,5 mg/kg Group | Heart Rate Variation | HR baseline/postintubation | -8 percentage of variation | Standard Deviation 15 |
| 2 Minute - 1,5 mg/kg Group | Heart Rate Variation | HR baseline/pre-intubation | 4 percentage of variation | Standard Deviation 8 |
| 2 Minute - 1,5 mg/kg Group | Heart Rate Variation | HR pre-intubation/postintubation | -12 percentage of variation | Standard Deviation 16 |
| 2 Minute - 1 mg/kg Group | Heart Rate Variation | HR baseline/postintubation | -9 percentage of variation | Standard Deviation 16 |
| 2 Minute - 1 mg/kg Group | Heart Rate Variation | HR baseline/pre-intubation | 4 percentage of variation | Standard Deviation 10 |
| 2 Minute - 1 mg/kg Group | Heart Rate Variation | HR pre-intubation/postintubation | -15 percentage of variation | Standard Deviation 20 |
| 1 Minute - 2 mg/kg Group | Heart Rate Variation | HR baseline/postintubation | -4 percentage of variation | Standard Deviation 17 |
| 1 Minute - 2 mg/kg Group | Heart Rate Variation | HR baseline/pre-intubation | 1 percentage of variation | Standard Deviation 11 |
| 1 Minute - 2 mg/kg Group | Heart Rate Variation | HR pre-intubation/postintubation | -5 percentage of variation | Standard Deviation 16 |
| 1 Minute - 1,5 mg/kg Group | Heart Rate Variation | HR baseline/postintubation | -5 percentage of variation | Standard Deviation 20 |
| 1 Minute - 1,5 mg/kg Group | Heart Rate Variation | HR baseline/pre-intubation | 4 percentage of variation | Standard Deviation 15 |
| 1 Minute - 1,5 mg/kg Group | Heart Rate Variation | HR pre-intubation/postintubation | -10 percentage of variation | Standard Deviation 19 |
| 1 Minute - 1 mg/kg Group | Heart Rate Variation | HR baseline/pre-intubation | 5 percentage of variation | Standard Deviation 14 |
| 1 Minute - 1 mg/kg Group | Heart Rate Variation | HR pre-intubation/postintubation | -17 percentage of variation | Standard Deviation 19 |
| 1 Minute - 1 mg/kg Group | Heart Rate Variation | HR baseline/postintubation | -10 percentage of variation | Standard Deviation 18 |
Primary
Systolic Blood Pressure Variation
Non-invasive systolic blood pressure change (%) at baseline, pre-intubation and postintubation. Positive results mean percentage reduction in SBP between the studied moments. Negative results mean percentage increase in SBP between the studied moments.
Time frame: Baseline before fentanyl administration, pre-intubation after propofol and bispectral index<60 and postintubation 15 seconds after endotracheal tube positioned
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 Minute - 2 mg/kg Group | Systolic Blood Pressure Variation | SBP baseline/postintubation | 11 percentage of variation | Standard Deviation 22 |
| 2 Minute - 2 mg/kg Group | Systolic Blood Pressure Variation | SBP baseline/pre-intubation | 26 percentage of variation | Standard Deviation 16 |
| 2 Minute - 2 mg/kg Group | Systolic Blood Pressure Variation | SBP pre-intubation/postintubation | -22 percentage of variation | Standard Deviation 27 |
| 2 Minute - 1,5 mg/kg Group | Systolic Blood Pressure Variation | SBP baseline/postintubation | 8 percentage of variation | Standard Deviation 15 |
| 2 Minute - 1,5 mg/kg Group | Systolic Blood Pressure Variation | SBP baseline/pre-intubation | 23 percentage of variation | Standard Deviation 12 |
| 2 Minute - 1,5 mg/kg Group | Systolic Blood Pressure Variation | SBP pre-intubation/postintubation | -21 percentage of variation | Standard Deviation 28 |
| 2 Minute - 1 mg/kg Group | Systolic Blood Pressure Variation | SBP baseline/postintubation | 9 percentage of variation | Standard Deviation 19 |
| 2 Minute - 1 mg/kg Group | Systolic Blood Pressure Variation | SBP baseline/pre-intubation | 18 percentage of variation | Standard Deviation 13 |
| 2 Minute - 1 mg/kg Group | Systolic Blood Pressure Variation | SBP pre-intubation/postintubation | -12 percentage of variation | Standard Deviation 17 |
| 1 Minute - 2 mg/kg Group | Systolic Blood Pressure Variation | SBP baseline/postintubation | 14 percentage of variation | Standard Deviation 18 |
| 1 Minute - 2 mg/kg Group | Systolic Blood Pressure Variation | SBP baseline/pre-intubation | 22 percentage of variation | Standard Deviation 11 |
| 1 Minute - 2 mg/kg Group | Systolic Blood Pressure Variation | SBP pre-intubation/postintubation | -12 percentage of variation | Standard Deviation 21 |
| 1 Minute - 1,5 mg/kg Group | Systolic Blood Pressure Variation | SBP baseline/postintubation | 16 percentage of variation | Standard Deviation 19 |
| 1 Minute - 1,5 mg/kg Group | Systolic Blood Pressure Variation | SBP baseline/pre-intubation | 18 percentage of variation | Standard Deviation 13 |
| 1 Minute - 1,5 mg/kg Group | Systolic Blood Pressure Variation | SBP pre-intubation/postintubation | -3 percentage of variation | Standard Deviation 16 |
| 1 Minute - 1 mg/kg Group | Systolic Blood Pressure Variation | SBP baseline/pre-intubation | 17 percentage of variation | Standard Deviation 13 |
| 1 Minute - 1 mg/kg Group | Systolic Blood Pressure Variation | SBP pre-intubation/postintubation | -12 percentage of variation | Standard Deviation 16 |
| 1 Minute - 1 mg/kg Group | Systolic Blood Pressure Variation | SBP baseline/postintubation | 8 percentage of variation | Standard Deviation 16 |
Primary
Systolic Blood Pressure Variation in Elderly (>55y)
Non-invasive SBP change (%) in patients \> 55 years at baseline, pre-intubation and postintubation. Positive results mean percentage reduction in SBP between the studied moments. Negative results mean percentage increase in SBP between the studied moments.
Time frame: Baseline before fentanyl administration, pre-intubation after propofol and bispectral index<60 and postintubation 15 seconds after endotracheal tube positioned
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 Minute - 2 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP baseline/postintubation | 19 percentage of variation | Standard Deviation 22 |
| 2 Minute - 2 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP baseline/pre-intubation | 36 percentage of variation | Standard Deviation 12 |
| 2 Minute - 2 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP pre-intubation/postintubation | -27 percentage of variation | Standard Deviation 32 |
| 2 Minute - 1,5 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP baseline/postintubation | 10 percentage of variation | Standard Deviation 14 |
| 2 Minute - 1,5 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP baseline/pre-intubation | 26 percentage of variation | Standard Deviation 12 |
| 2 Minute - 1,5 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP pre-intubation/postintubation | -23 percentage of variation | Standard Deviation 30 |
| 2 Minute - 1 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP baseline/postintubation | 13 percentage of variation | Standard Deviation 19 |
| 2 Minute - 1 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP baseline/pre-intubation | 21 percentage of variation | Standard Deviation 13 |
| 2 Minute - 1 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP pre-intubation/postintubation | -10 percentage of variation | Standard Deviation 16 |
| 1 Minute - 2 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP baseline/postintubation | 22 percentage of variation | Standard Deviation 15 |
| 1 Minute - 2 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP baseline/pre-intubation | 29 percentage of variation | Standard Deviation 6 |
| 1 Minute - 2 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP pre-intubation/postintubation | -10 percentage of variation | Standard Deviation 23 |
| 1 Minute - 1,5 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP baseline/postintubation | 22 percentage of variation | Standard Deviation 17 |
| 1 Minute - 1,5 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP baseline/pre-intubation | 21 percentage of variation | Standard Deviation 13 |
| 1 Minute - 1,5 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP pre-intubation/postintubation | 2 percentage of variation | Standard Deviation 13 |
| 1 Minute - 1 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP baseline/pre-intubation | 22 percentage of variation | Standard Deviation 13 |
| 1 Minute - 1 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP pre-intubation/postintubation | -15 percentage of variation | Standard Deviation 19 |
| 1 Minute - 1 mg/kg Group | Systolic Blood Pressure Variation in Elderly (>55y) | SBP baseline/postintubation | 12 percentage of variation | Standard Deviation 13 |
Secondary
Number of Patients Who Needed Vasoactive Drug
Patients who suffered SPB reduction \> 30% or SPB \< 90mmHg, receive vasoactive drugs
Time frame: 1 minute after intubation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 2 Minute - 2 mg/kg Group | Number of Patients Who Needed Vasoactive Drug | 4 Participants |
| 2 Minute - 1,5 mg/kg Group | Number of Patients Who Needed Vasoactive Drug | 1 Participants |
| 2 Minute - 1 mg/kg Group | Number of Patients Who Needed Vasoactive Drug | 0 Participants |
| 1 Minute - 2 mg/kg Group | Number of Patients Who Needed Vasoactive Drug | 2 Participants |
| 1 Minute - 1,5 mg/kg Group | Number of Patients Who Needed Vasoactive Drug | 3 Participants |
| 1 Minute - 1 mg/kg Group | Number of Patients Who Needed Vasoactive Drug | 0 Participants |
Secondary
Time to Hypnosis
Bispectral index (BIS)\<60 meaning general anesthesia, BIS\>60 meaning mild/moderate sedation. We measure the time until patient reachs hypnosis
Time frame: After administration of propofol, time is measured in seconds until BIS values are less than 60
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 Minute - 2 mg/kg Group | Time to Hypnosis | 54 seconds | Standard Deviation 29 |
| 2 Minute - 1,5 mg/kg Group | Time to Hypnosis | 49 seconds | Standard Deviation 27 |
| 2 Minute - 1 mg/kg Group | Time to Hypnosis | 62 seconds | Standard Deviation 34 |
| 1 Minute - 2 mg/kg Group | Time to Hypnosis | 41 seconds | Standard Deviation 20 |
| 1 Minute - 1,5 mg/kg Group | Time to Hypnosis | 47 seconds | Standard Deviation 15 |
| 1 Minute - 1 mg/kg Group | Time to Hypnosis | 67 seconds | Standard Deviation 42 |