Effect of Various Injection Speeds of Propofol on Blood Pressure, Time Taken and Dose Required for Induction of Anesthesia: A Prospective Observational Study
Background: To investigate the effect of injection speed of Propofol for induction of anesthesia primarily on blood pressure and secondarily, on time taken for induction of anesthesia and dose of propofol required. Methods: The prospective & interventional, randomized single blind comparative study conducted on 90 patients of both sexes aged 25-55 years of ASA grade I/II admitted to Paras Hospital Gurugram India, a tertiary care Centre, for elective surgeries under general anesthesia. Results: Mean age, sex, weight, height and distribution of patients as per ASA status was comparable among all the three groups as statistically P values were not significant (all P Value = >0.05). The differences of mean dose of Propofol used in mg and mg/kg for induction, mean induction time (seconds), pre and post induction mean systolic blood pressure (mmHg), mean diastolic blood pressure (mmHg) and mean arterial pressure (mmHg) among the studied groups (P50, P100, and inP200) were statistically significant with a p value of <0.05. There was no statistically significant difference between pre and post induction mean heart rate and oxygen saturation. Conclusion: At faster speeds of injection of Propofol, larger doses are required for induction of anesthesia and significant drop in systolic, diastolic and mean arterial pressures while as the time taken for induction of anesthesia was shorter when compared to the injection at slower speeds.
Introduction
Propofol is preferred over Thiopentone sodium for induction of anesthesia but one of the disadvantages of Propofol is significant hypotension. A typical induction dose of Propofol 2mg/kg body weight results in approximately 30% reduction in systolic blood pressure [1]. The hypotensive effect of Propofol is attributable to a decrease in sympathetic activity, direct vasodilatation and myocardial depression [2]. This fall in blood pressure is of little significance in normal healthy patients but can be of great significance in patients who have coronary artery disease etc. because it can lead to myocardial ischemia. Blood concentration of Propofol depends on many factors such as age, gender, body weight, dose, cardiac output and infusion rate [2, 3, 4].
The effect of different injection rates of Propofol on hemo dynamics, induction time and dose required for induction of anesthesia has been investigated in several studies [5, 6, 7, 8]. In most of the studies it was observed that decrease in blood pressure was significantly less in patients in whom the drug was injected at a slower speed although there was a slight delay in induction time which was statistically significant and also there was a slight decrease in the dose of Propofol which was also statistically significant, for induction of anesthesia.
Dose requirements of Propofol induction depend on patient characteristics and infusion rate [8] Cardiac output (CO) is thought to be an important factor affecting the induction of anesthesia [9] Particularly high concentrations could be expected if a normal dose of Propofol was injected into a patient with low CO. Consistent with the experience of most anesthesiologists, critically ill patients with low CO usually require very small doses of Propofol [10].
The mechanism of hypotension is attributed to a decrease in sympathetic activity [11], myocardial depression [12], and direct vasodilation [12, 13]. Hypotensive effects of Propofol are generally proportional to the dose and rate of administration [12, 14, 15]. Induction with Propofol is known to cause decrease in blood pressure. Studies have demonstrated up to a 28% decrease in SBP, an 11% decrease in MAP, and a 19% decrease in DBP [12, 16]. When Propofol is administered as a 2 mg/kg IV bolus, SBP decreased by 20%. There was also a decrease in DBP and MAP by 16% and 19% respectively. In a recent study, Cheng et al has proposed a molecular pathway that may contribute to vasodilatory effect of Propofol [17]. Due to the inhibitory effect of Propofol on baroreflexes and sympathetic activity, the effect of Propofol on heart rate is variable with many studies showing decrease in heart rate [18, 19].
Several studies with varied methods of delivery have demonstrated reduced hemodynamic effects and a decrease in dose requirements of Propofol. Studies have also shown that a slower injection of Propofol decreases cardiovascular effects [20, 21]. However, slow injection may also result in longer induction times. In a recent study using a target controlled infusion (TCI), Liu, et al. [22] demonstrated that the decrease in SBP was significantly less when Propofol was given in a step wise technique with an initial plasma concentration of 2.0 mg/ml and then raised to a target plasma concentration of 4.0 mg/ml [23].
The objective in the present study is to investigate the effect of injection speed of Propofol for induction of anesthesia primarily on blood pressure and secondarily, on time taken for induction of anesthesia and dose of propofol required.
Methodology
The was prospective & interventional, randomized single blind comparative study conducted on 90 patients of both sexes aged 25-55 years of ASA grade I/II admitted to Paras Hospital Gurugram India, a tertiary care Centre, for elective surgeries under general anesthesia after taking clearance from ethical and scientific committee and after obtaining an informed written consent from every patient. The mean age, weight, height and ASA Status was comparable among all the groups.
Inclusion Criteria
- Patients in age group of 25-55 years
- ASA Grade I/II
- Elective surgeries
Exclusion Criteria
- Patients less than 25 and more than 55 years of age
- ASA Grade III/IV
- Emergency surgeries
- Known allergy to the study drug
- Patient’s refusal to participate in the study.
- Hypertensive patients
- Diabetic patients
A detailed pre-anesthetic checkup including history, general physical examination, and routine investigations as guided by age were carried out in all patients. After shifting the patient to the operating room, multichannel monitors were attached to the patient for recording the vital parameters like fasting status, Systolic blood pressure, Diastolic blood pressure, mean arterial pressure, ECG, Heart rate, End tidal CO2 and Oxygen saturation. All these vitals were recorded as baseline parameters.
1% Propofol was given in the form of injection manually using stop watch & 20ml disposable syringe, at three different rates of 50mg/min (1ml/12sec.) to the patients of group P50, 100mg/min (1ml/6sec.) to the patients of group P100 and 200mg/min (1ml/3sec.) to the patients of group P200 respectively until the loss of verbal contact. After that fentanyl (1mcg/kg) and atracurium (0.5mg/kg) were administered and anesthesia was maintained with isoflurane in 50% O2-N2O. Hypotension, time taken for induction and dose of Propofol (till loss of verbal contact) were compared among the three groups.
Results
In our study as illustrated in Table 1.
Statistical Analysis
Statistical analysis was done by SPSS Version 20.0 (SPSS Inc., Chicago, Illinois, USA). Continuous variables were expressed as Mean±SD and categorical variables were summarized as frequencies and percentages. Analysis of variance (ANOVA) with least significant difference (LSD) test was employed for comparing continuous variables. Chi-square test or Fisher’s exact test, whichever appropriate, was applied for comparing categorical variables. A P-value of less than 0.05 was considered statistically significant.
| P50 | P100 | P200 | P Value | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age (Years) | 37.6 (28-52) | 40.1 (26-55) | 39.2(25-55) | 0.546 | ||||||||||
| 14 (46.7%)/16(53.3%) | 17 (56.7%)/13(43.3 %) | 16 (53.3%)/14(46.7%) | 0.732 | |||||||||||
| Gender M/F | ||||||||||||||
| Weight Kg | 68.3 (57-79) | 69(58-77) | 68.5(53-80) | 0.898 | ||||||||||
| Height | 163.2(154-174) | 162.1(156-168) | 163.8(157-175) | 0.338 |
Table 1: Parameters of patients of all groups.
Mean age in group P50 was 37.6±6.13 years (range 28-52), group P100 was 40.1±9.15 years (range 26-55) and in group P200 was 39.2±9.86 years (range 25-55) with p value of 0.546. Out of 30 patients, in group P50 14(46.7%) were males and 16 (53.3%) were female, in group P100 17 (56.7%) were males and 13 (43.3%) were females, in group P200 16 (53.3) were males and 14 (46.7) were females. P value =0.732. Mean weight in group P50 being 68.3± 5.86kg (range 57-79), group P100 being 69.0±5.49kgs (range 58-77) and group P200 68.5±6.67kg (range 53-80) with a p value=0. 898. Mean height in group P50 being 163.2±5.29cm (range 154- 174), group P200 being 162.1±3.03cms (range 156-168) and group P200 163.8±4.27cms (range 157-175) with a p value of =0.338. Table 2 shows distribution of patients as per ASA status with 24 (80.0%).
| ASA I | ASA II | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Group | P-value | ||||||||||||||||
| No. | Percentage | No. | Percentage | ||||||||||||||
| P50 | 24 | 80 | 6 | 20 | 0.627 | ||||||||||||
| P100 | 22 | 73.3 | 8 | 26.7 | |||||||||||||
| P200 | 25 | 83.3 | 5 | 16.7 |
Table 2: Distribution of patients as per ASA status.
Patients of group P50 in ASA I and 6 (20.0%) in ASA II. In group P100 there were 23 (73.3%) and 8 (26.7%) patients in ASA I and ASA II. There were 25 (83.3%) patients of group P200 in ASA I and 5 (16.7%) patients with ASA II. When compared statistically P value of 0.627 was calculated.
statistically difference P values were not significant. (All P Value = >0.05) as shown in Table 1. The mean total dose of Propofol used (mg) for induction among the studied groups was 101.2+7.79, in P50 (range 89-112), p-value <0.001, 152.7+7.71 in P100 with (range 139-164), p value <0.001, and in group P200 the mean dosage was 207.4+8.06 with a (range of 192-219), p –value <0.001. The difference was statistically significant with a p value of < 0.05 (Table 3).
Since, mean age, sex, weight, height and ASA status was comparable among all the three groups as
| Propofol Amount (mg) | Mean | SD | Range | Comparison | P-value | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P50 | 101.2 | 7.79 | 89-112 | P50 vs P100 | <0.001* | ||||||||||||
| P100 | 152.7 | 7.71 | 139-164 | P100 vs P200 | <0.001* | ||||||||||||
| P200 | 207.4 | 8.06 | 192-219 | P200 vs P50 | <0.001* |
Table 3: Showing calculated propofol dose during induction (mg/kg) among various groups. *Statistically Significant Difference (P
- The mean dose per kg body weight of Propofol used
- (mg/kg) for induction among the studied groups, in P50 was 1.49+0.029 (range 1.2-1.8) with p- value <0.001, in
- P100 was 2.23+0.038 (range 1.8-2.7) with p value <0.001, and in group P200 the mean dosage was 3.07+0.061 with a range of 2.4-4.1, p value <0.001. The difference was statistically significant (p value <0.05) in all the groups
- (Table 4).
- Groups mg/kg
- SD
- Range
- Comparison
- P value
- P50
- 1.49
- 0.029
- 1.2-1.8
- P50 vs P100
- <0.001*
- P100
- 2.23
- 0.038
- 1.8-2.7
- P100 vs P200
- <0.001*
- P200
- 3.07
- 0.061
- 2.4-4.1
- P200 vs P50
- <0.001*
- P50
- 1.49
- 0.029
- 1.2-1.8
- P50 vs P100
- <0.001*
Table 4: Showing calculated propofol dose during induction (mg/kg) among various groups.
| Induction time (seconds) | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Groups | Comparison | P-value | |||||||||||||||
| Mean | SD | Range | |||||||||||||||
| P50 | 121.9 | 8.26 | 107-134 | P50 vs P100 | <0.001* | ||||||||||||
| P100 | 89.4 | 6.51 | 78-99 | P100 vs P200 | <0.001* | ||||||||||||
| P200 | 60.8 | 7.01 | 50-73 | P200 vs P50 | <0.001* |
Table 5: Comparison based on induction time (seconds) among different groups. *Statistically Significant Difference (P-value<0.05
122.5+4.41 and 91.1+3.89 respectively. The difference was statistically significant with a p <0.05 (Table 6).
| Systolic blood pressure (SBP) | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Groups | Before Induction | After Induction | Diff. in SBP | P-value (ANOVA) | ||||||||||||||||
| Mean | SD | Mean | SD | |||||||||||||||||
| P50 | 123.1 | 6.26 | 109.8 | 5.13 | 13.3 | <0.001 | ||||||||||||||
| P100 | 122.6 | 4.5 | 99.7 | 4.35 | 22.9* | |||||||||||||||
| P200 | 122.5 | 4.41 | 91.1 | 3.89 | 31.5 |
Table 6: Comparison of changes in systolic blood pressure (mmHg) before and after induction among different groups.
The mean diastolic blood pressure (mmHg) pre and post induction was 81.6+3.99 and 75.5+2.90 in P50, 82.1+2.81and 74.8+1.89 in P100 and 80.8+3.23 and
66.9+2.63 in group P200 respectively. The difference was statistically significant with a p <0.001 (Table 7).
| Diastolic blood pressure (DBP) | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Groups | Before Induction | After Induction | Diff. in DBP | P-value (ANOVA) | ||||||||||||||
| Mean | SD | Mean | SD | |||||||||||||||
| P50 | 81.6 | 3.99 | 75.5 | 2.9 | 6.1 | <0.001 | ||||||||||||
| P100 | 82.1 | 2.81 | 74.8 | 1.89 | 11.0* | |||||||||||||
| P200 | 80.8 | 3.23 | 66.9 | 2.63 | 13.9** |
Table 7: Comparison of changes in diastolic blood pressure (mmHg) before and after induction among different groups. *Statistical
Table 7: Comparison of changes in diastolic blood pressure (mmHg) before and after induction among different groups. *Statistically Significant Difference (P-value<0.05) Compared with P50 ** Statistically Significant Difference (P-value<0.05) Compared to P50 and P100 The mean arterial pressure (mmHg) pre and post induction was 95.4+4.61 and 86.9+3.52 in P50, 95.6+3.25 and 80.7+2.53 in P100 and 94.7+3.52 and 74.9+2.75 in group P200 respectively. The difference was statistically significant with a p <0.05 (Table 8).
| Mean arterial pressure (MAP) | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P-value | ||||||||||||||||||
| Groups | Before Induction | After Induction | Diff. in MAP | |||||||||||||||
| (ANOVA) | ||||||||||||||||||
| Mean | SD | Mean | SD | |||||||||||||||
| P50 | 95.4 | 4.61 | 86.9 | 3.52 | 8.5 | <0.001 | ||||||||||||
| P100 | 95.6 | 3.25 | 80.7 | 2.53 | 14.9* | |||||||||||||
| P200 | 94.7 | 3.52 | 74.9 | 2.75 | 19.8** |
Table 8: Comparison of changes in mean arterial pressure (mmHg) before and after induction among different groups. *Statistically
Table 8: Comparison of changes in mean arterial pressure (mmHg) before and after induction among different groups. *Statistically Significant Difference (P-value<0.05) Compared with P5 ** Statistically Significant Difference (P-value<0.05) Compared to P50 and P100 There was no statistically significant difference between pre and post induction mean heart rate and oxygen saturation. The mean heart rate (bpm) pre and post induction was 87.9+4.40 and 83.5+4.51 in P50, 88.4+3.60 and 83.6+3.70 in P100 and 88.5+4.43 and
84.2+4.53 in group P200 respectively (P value >0.05). The mean oxygen saturation (%) pre and post induction was 99.2+1.02 and 98.1+1.12 in P200, 98.6+1.0 and 97.9+1.68 in P100 and was 99.1+0.99 and 98.2+1.10 in group P200 respectively ( P value >0.05) (Table 9).
| Heart Rate (HR) | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P-value | ||||||||||||||||||
| Groups | Before Induction | After Induction | Diff. in HR | |||||||||||||||
| (ANOVA) | ||||||||||||||||||
| Mean | SD | Mean | SD | |||||||||||||||
| P50 | 87.9 | 4.4 | 83.5 | 4.51 | 4.4 | 0.861 | ||||||||||||
| P100 | 88.4 | 3.6 | 83.6 | 3.7 | 4.8 | |||||||||||||
| P200 | 88.5 | 4.43 | 84.2 | 4.53 | 4.3 |
Table 9: Comparison of changes in heart rate (beats/min) before and after induction among different groups. *Statistically Signif
Discussion
In our study gender & age wise distribution, mean weight, mean height were all statistically comparable. This was consistent with findings of Sennur Uzun, et al. [24] who in their study of 72 patients showed mean age was 38±10 in P200, 43±11 in P300 and 40±14 in P400, male to female ratio was 8/16 in p200,12/12in p300 and7 /17 in p400. The mean weight was 70.7±14.4 in P 200, 77.5±14.2 in P 300 and 75.3±17.6in p400. The mean height was 165±9in p200, 169±11in p300 and 168±10 in p400.
Statistical no significant difference was found between three groups P value= 0.627 when patients were distributed as per ASA status. Kazama T, et al. [2] in their study the subjects of the study were 250 patients classified as American Society of Anesthesiologists physical status I or II aged 25-55 years which is similar to our finding.
In our study it was observed that as the rate of infusion increased, larger Propofol doses were required which, in their study the total dose used was (1.2, 1.6 and 2.5 mg kg-1 in groups 1,2,3. respectively). Similar results were shown by Stokes DN, et al. [8] Sennur Uzun, et al & Lie, et al. [24, 25] in their studies.
The mean induction time in our study was shorter in P200 when compared to P50 and P100 and the difference between three groups was statistically significant with p value <0.05. This showed resemblance with the study conducted by Rolly G, et al. [6] who in their study showed mean induction time increased from 21.5 to 34.7 and 50.5 s, when injection time was increased from 5 to 20 to 60 s, respectively. Mean induction time in studies conducted by Sennur Uzun, et al & Lie et al. [24, 25] is same as present in our study.
- SPO2
- Groups
- Diff.in spo2
- P-value (ANOVA)
- Before Induction
- After Induction
- Mean
- SD
- Mean
- SD
- P50
- 99.2
- 1.02
- 98.1
- 1.12
- 1.1
- 0.542
- P100
- 98.6
- 1
- 97.9
- 1.68
- 0.8
- P200
- 99.1
- 0.99
- 98.2
- 1.1
- 0.9
Table 10: Comparison of changes in SPo2 before and after induction among different groups.
| 100mg/min to 200mg/min. Li Q, et al. [25] | In their study | ||
|---|---|---|---|
| showed decrease in systolic and diastolic arterial | |||
| pressure was significantly less in the 300-ml h-1 group at | |||
| the end of induction and immediately after induction (P< | |||
| 0.01). | Sennur Uzun, | et al. [24] in their study also observed |
Table 11: Comparison of changes in SPo2 before and after induction among different groups.
In our study, the mean heart rate (bpm) and mean oxygen saturation (%) (Pre and post induction) showed no statistical significant change. This finding was supported by Rolly G, et al. [6] who also shows statistical insignificant changes in heart rate apnea, and saturation in their respective studies.
Conclusion
This study concludes that at faster speeds of injection of Propofol, larger doses are required for induction of anesthesia as compared to the doses required at slower speeds. Also, faster speeds of injection of propofol are associated with a significant drop in systolic, diastolic sand mean arterial pressures while as the time taken for induction of anesthesia was shorter when compared to the injection at slower speeds.
Limitations of this study were, injection of the drug manually to deliver it at accurate speeds is liable to errors, subjective assessment of induction by loss of verbal contact and small sample size.
Acknowledgment
The authors are highly thankful to the hospital administration, the paramedical staff of the anaesthetic department, hospital statistician, and computer operators for helping in conducting this research.
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