|Year : 2015 | Volume
| Issue : 2 | Page : 92-95
Priming effects of propofol during induction of anesthesia
Rilin Karlo, Nongthonbam Ratan Singh, Khullem Maniram Singh, Takhelmayum Hemjit Singh, Ningthoujam Anita Devi, Maharambam Binarani Devi
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Web Publication||20-Aug-2015|
Takhelmayum Hemjit Singh
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal - 795 004, Manipur
Source of Support: None, Conflict of Interest: None
Background: The "priming principle" is a method to reduce the total dose requirements of a drug. This study was carried out to evaluate whether the priming technique reduces the total induction dose requirements of propofol. Materials and Methods: Fifty (50) patients with American Society of Anesthesiologists (ASA) I and ASA II grades, of both sexes, aged 18-65 years, and undergoing elective surgical procedures under general anesthesia were randomly allocated into two equal groups with 25 patients each. Group I (control) received 3 mL of normal saline (placebo) intravenously (IV) as priming 2 min prior to the calculated dose of injection (inj.) propofol. Group II (study) received 0.5 mg/kg of inj. propofol as the priming dose 2 min prior to receiving a titrated dose of propofol. The titrated dose of propofol was given till loss of the eyelash reflex or loss of verbal command. Baseline hemodynamic variables were recorded at 2 min after priming and immediately after the titrated dose of propofol. Results: The hemodynamic changes in the heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) at different time intervals were similar in both groups (P > 0.05). The control group consumed a higher dose of inj. propofol (119.84 ± 12.28 mg) as compared with the study group (107.58 ± 14.73 mg), i.e., there was 10.23% reduction of the total dose in the study group. Most of the patients (80%) in both the groups were without any associated side effects and the incidence was similar (P = 1.00). Conclusion: The priming technique effectively reduced the total induction dose requirements of propofol and minimized periintubation hemodynamic alterations with minimal adverse effects.
Keywords: General anesthesia, Induction dose, Priming, Propofol
|How to cite this article:|
Karlo R, Singh NR, Singh KM, Singh TH, Devi NA, Devi MB. Priming effects of propofol during induction of anesthesia. J Med Soc 2015;29:92-5
|How to cite this URL:|
Karlo R, Singh NR, Singh KM, Singh TH, Devi NA, Devi MB. Priming effects of propofol during induction of anesthesia. J Med Soc [serial online] 2015 [cited 2021 Apr 17];29:92-5. Available from: https://www.jmedsoc.org/text.asp?2015/29/2/92/163198
| Introduction|| |
Propofol has been established as an excellent intravenous anesthetic agent because of its fast onset and short duration of action, clear-headed recovery,  better intubating conditions, and minimal postoperative complications. However, rapid induction with a conventional dose of propofol is associated with fall in the blood pressure (BP) and local pain, which is dose-dependent. 
Thus, a reduction in the induction dose would reduce the associated side effects. Various methods have been studied for reducing the induction dose requirements of propofol, but all of them have their own side effects, such as excess sedation, hypotension, and respiratory depression. A constant search for an ideal method to reduce the induction dose requirements of propofol continued, until finally an alternative method was introduced as the "priming principle." 
The priming principle or autocoinduction is a technique of giving a precalculated dose of the induction agent prior to giving the full dose of the same induction agent. It is a technique that is reliable, effective, and safe for the patient.  Application of the "priming principle" is a well-known practice with use of nondepolarizing muscle relaxants wherein "priming" shortens the onset of neuromuscular blockade and provides better intubating conditions. , Some workers have used benzodiazepines or opioids along with routine premedication agents.  These drugs have a synergistic effect with induction agents , and thereby may mask the actual priming effect of propofol.
We therefore conducted this study to evaluate whether the priming principle really reduces the total induction dose requirements of propofol and its associated hemodynamic changes without the additional use of agents with synergistic effect.
| Materials and methods|| |
After institutional Ethical Committee approval, a randomized double-blinded study was conducted at the Department of Anesthesiology at a tertiary teaching hospital in Imphal. After obtaining written informed consent, American Society of Anesthesiologists (ASA) Grade I and II patients of both sexes, 18-65 years of age, and undergoing elective surgical procedures were allocated by computer-generated randomization into two groups. Based on a previous study,  a total of 50 patients were recruited considering an α value = 0.05, desired power = 0.8, and a sample size of 24; the number of patients was calculated and rounded to 25 patients in each group.
Group I: Received 3 mL of normal saline intravenously.
Received 25% of calculated dose of 2 mg/kg, i.e., 0.5 mg/kg of propofol intravenously (IV) as priming dose 2 min before the remaining induction dose.
Patients allergic to the proposed study medication, pregnant and lactating woman, patients with anticipated difficult intubation, and hemodynamically compromised patients were excluded from the study. To prevent bias, the study drugs were prepared and administered by a colleague not involved in the study.
After recording the baseline hemodynamic parameters and preoxygenation, the priming dose was given at a rate of 3 mL/10 min, i.e., 30 mg/10 min, followed 2 min later by the remaining dose of propofol by titration method till the loss of verbal command or loss of eyelash reflex, in both the groups. Hemodynamic parameters such as BP, heart rate (HR), saturation of peripheral oxygen (SpO 2 ), and electrocardiogram (ECG) were recorded every 2 min after priming and immediately after the titrated dose. Adverse effects, if any, were noted.
| Results|| |
Demographic characteristics in the two groups were comparable in the two groups and statistically not significant; P = 0.89 [Table 1].
The HR recorded a maximum value at 2 min after priming and a minimum value after induction in both the control and study groups. This trend of changes in the HR rate at different time intervals was similar in both the groups [P < 0.05; [Table 2]].
|Table 2: Showing the mean heart rate (HR/min) at different time intervals|
Click here to view
A maximum value of systolic blood pressure (SBP) was recorded at 2 min after priming with a minimum value after induction in both the groups. This trend in the changes of SBP, as shown in [Table 3], is not different and statistically not significant. Similar findings were observed with the diastolic blood pressure (DBP) [Table 4].
The control group consumed a higher dose of inj. propofol (119.84 ± 12.28 mg) as compared with the study group (107.58 ± 14.73 mg). This 10.23% reduction of the total dose in the study group, as shown in [Table 5] and [Figure 1], is statistically significant (P = 0.02).
|Figure 1 : Showing mean induction total dose of propofol (mg) in the two groups (P = 0.02)|
Click here to view
[Table 5] shows the distribution of adverse effects in the two groups. Most of the patients (80%) in both the groups were without any associated side effects, while 16% and 4% of patients in both the groups were associated with pain on injection and hypotension respectively. However, this distribution in the incidence of adverse effects is similar in both the groups and statistically not significant (P = 1.00).
| Discussion|| |
Rapid induction with a conventional dose of propofol is associated with fall in the BP and local pain, which is dose-dependent.  To reduce the induction dose requirements of propofol, the concurrent use of synergistic drugs such as nitrous oxide,  methylene blue,  esmolol,  α2-agonist, , magnesium,  opioids,  barbiturates,  and benzodiazepines such as midazolam  and ketamine  is usually practiced, but all of them have their own side effects, such as excess sedation, hypotension, and respiratory depression.
In our study, we used 25% (0.5 mg/kg) of the calculated dose, taking a conventional dose of propofol at 2 mg/kg. Most of the studies related to the priming principle were done with concomitant use of synergistic agents, which we thought could have masked the actual effect of this method.
Changes in the HR following propofol priming in this study varied from other studies, such as those of Claeys et al.  and Pensado et al.,  who observed that there was no associated change in the HR following induction with 2 mg/kg of propofol. They attributed it to the concurrent use of nitrous oxide during induction with propofol, which appears to induce marked "resetting" of the HR baroreflex set point to allow lower arterial pressures without tachycardia and myocardial depression pronounced by other medications used in their study. There is also increase in SBP compared to baseline, i.e., increase from 126.48 ± 13.69 mmHg to 129.88 ± 17.48 mmHg at 2 min after priming in the study group compared to increase from 127.96 ± 13.10 mmHg to 131.76 ± 10.28 mmHg in the control group, in our study. This difference could be explained by the fact that we did not use anxiolytic premedication in this study, which might have caused sympathetic stimulation as supported by increase in HR and subsequent increase in cardiac output.
The SBP fell to 114.40 ± 16.01 mmHg from 126.48 ± 13.69 mmHg after induction in the study group and from 121.80 ± 15.60 mmHg to 127.96 ± 13.10 mmHg in the control group. This decrease could be due to the higher induction dose used in the control group because propofol causes dose-dependent decreases in SBP subsequent to its lowering of systemic vascular resistance, as justified by Pensado et al. 
The overall incidence of various adverse effects upon induction with propofol was 20% in both groups. The adverse effects observed were pain on injection (16%) and hypotension (4%) in both groups. Pain on injection with propofol is a common adverse effect, the cause of which remains unknown.  Contrary to some similar previous studies,  succinylcholine-induced fasciculation was not observed in this study.
All the patients with clinically observed apnea (>30 s) were given intermittent positive-pressure ventilation with bag and mask with 100% O 2 , and hypotension was treated with crystalloids. The fall in the BP was transient and rarely required any drug therapy.
| Conclusion|| |
Based on the results obtained from our study, we conclude that the application of the "priming principle" indeed marginally reduces the total induction dose requirements of propofol by 10.23%, and is associated with minimal periintubation hemodynamic alterations and adverse effects, although these are statistically not significant.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kanto JH. Propofol, the newest induction agent of anesthesia. Int J Clin Pharmacol Ther Toxicol 1988;26:41-57.
Gillies GW, Lees NW. The effects of speed of injection on induction of propofol. A comparison with etomidate. Anaesthesia 1989;44:386-8.
Anderson L, Robb HA. A comparison of midazolam co-induction with propofol predosing for induction of anaesthesia. Anaesthesia 1998;53:1117-20.
Djaiani G, Ribes-Pastor MP. Propofol auto-co-induction as an alternative to midazolam co-induction for ambulatory surgery. Anaesthesia 1999;54:63-7.
Donati F. The priming saga: Where do we stand now? Can J Anaesth 1988;35:1-4.
Baumgarten RK, Carter CE, Reynolds WJ, Brown JL, DeVera HV. Priming with nondepolarizing relaxants for rapid tracheal intubation: A double-blind evaluation. Can J Anaesth 1988;35:5-11.
Arekapudi AK, Sanicop CS, Kotur PF. Effect of priming principle on the induction dose requirements of propofol - A randomized clinical trial. Indian J Anaesth 2006;50:283-7.
Cressey DM, Claydon P, Bhaskaran NC, Reilly CS. Effects of midazolam pre-treatment on induction dose requirements of propofol in combination with fentanyl in younger and older adults. Anaesthesia 2001;56:108-13.
Shlomo B, Finger J, Bar-Av E, Perl AZ, Etchin A, Tverskoy M. Propofol and fentanyl act additively for induction of anaesthesia. Anaesthesia 1993;48:111-3.
Ng JM, Hwang NC. Inhaling nitrous oxide reduces the induction dose requirements of propofol. Anesth Analg 2000;90:1213-6.
Licker M, Diaper J, Robert J, Ellenberger C. Effects of methylene blue on propofol requirement during anaesthesia induction and surgery. Anaesthesia 2008;63:352-7.
Wilson ES, McKinlay S, Crawford JM, Robb HM. The influence of esmolol on the dose of propofol required for induction of anaesthesia. Anaesthesia 2004;59:122-6.
Altan A, Turgut N, Yildiz F, Türkmen A, Ustün H. Effects of magnesium sulphate and clonidine on propofol consumption, haemodynamics and postoperative recovery. Br J Anaesth 2005;94:438-41.
Morris J, Acheson M, Reeves M, Myles PS. Effect of clonidine pre-medication on propofol requirements during lower extremity vascular surgery: A randomized controlled trial. Br J Anaesth 2005;95:183-8.
Naguib M, Sari-Kouzel A. Thiopentone-propofol hypnotic synergism in patients. Br J Anaesth 1991;67:4-6.
Srivastava U, Sharma N, Kumar A, Saxena S. Small dose propofol or ketamine as an alternative to midazolam co-induction to propofol. Indian J Anaesth 2006;50:112-4.
Claeys MA, Gepts E, Camu F. Hemodynamic changes during anaesthesia induced and maintained with propofol. Br J Anaesth 1988;60:3-9.
Pensado A, Molins N, Alvarez J. Haemodynamic effects of propofol during coronary artery bypass surgery. Br J Anaesth 1993;71:586-8.
Tan CH, Onsiong MK. Pain on injection of propofol. Anaesthesia 1998;53:468-76.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]