Use of Lidocaine and Sodium Thiopental for Pain Management

Different premedication admixture with propofol to attenuate pain severity


induced by propofol injection:


a double blind randomized controlled clinical trial

Abstract

Background and Objective

Propofol has widely used due to providing pleasant anesthesia and rapid recovery. However; injection pain is one of the main side effects of a propofol that has remained as an undesirable problem. This study compares the effect of thiopental, lidocaine, fentanyl , normal saline admixture with propofol compared with only propofol on injection pain induced by propofol

Materials and methods

A double blind randomized controlled clinical trial was conducted on 257 patients that were randomly allocated to one of five groups to receive only 2mg/kg of Propofol type Fresenius One percent in group I, 2 cc of Lidocaine 1% in group II, 2 ml of Normal Saline 0.09% in group III, 50 mg Sodium Thiopental in Group IV and Group V were injected 100µg Fentanyl before injection of Propofol. Verbal Rating Scale was used for assessing pain.

Results

A significant decrease in pain severity during injection was achieved in group II (lidocaine ) and IV (Thiopental) compared to other groups. Fentanyl was also effective in reducing moderate pain.

Conclusion:

We found that Thiopental and lidocaine reduce more effectively incidence and pain severity than other groups. It seems that aforementioned drugs bee more appropriate as an alternative method to diminish propofol injection pain than others treatment in this study.

Key Word:


propofol, injection pain, premedication

Introduction

Preoperative care cause satisfaction for patient in recent years(1)Propofol is the drug that has attained popularity which has widely used owing to its fast onset time ,short-acting duration , and trivial adverse effects (2) despite these favorable attributes, the prevalence of injection pain has been reported 68-90% and has been ranked seventh among the 33 undesirable clinical problem in anesthesia(3-6). Injection pain severity was reported 5.6 ± 2.3 by measuring system of Visual Analog Scale , which represents unfavorable pain (7). Up to now, different ways have been studied and recommended to reduce the incidence and pain severity of Propofol injection. Among various methods,


emollient of Propofol (8, 9) and using numerous drugs including Lidocaine (10), Thiopental(11) ,Alfentanil (12) and Gransytron or Ondansetron(13)can be noted. There are different emollients of Propofol in Iran such as Fresenius Propofol 1% which has a side branch of a long triglyceride (LCT) and Lipuro Propofol 1% which has side branches of medium and long triglyceride (MCT/LCT) ,that is assuming that later one is more effective in reducing injection pain(14). Lidocaine as a local anesthetic inhibits the beginning and conduction of nervous impulses by decreasing the penetration of nerve membrane to Na+. It prevents the membrane depolarization, effluence and conduction of potential . It’s systemic absorption is rapid via skin and phlegm (throat, respiratory system) (15).Fentanyl is a drug which usually used as a premedication, because of the rapid and short onset, intense analgesia, Stable cardiovascular hemodynamic as well as less histamine release (16). Thiopental from barbiturate family causes hypotension but has a high ability to protect nerves and control ICP (17). Ondansetron is a modern antiemetic drug which is chosen as the antagonist of Hydroxyl Triptamin type 3. This drug reduces nausea and vomiting and its complications are also very low(18). Different advantages of aforementioned drugs for pain persuaded us to use them to understand that how much they can reduce propofol injection pain and which one is more effective.

Methods:

A double blind randomized controlled clinical trial was performed on 257 patients, after obtaining confirmation from both Golestan University of medical science and 5th Azar hospital ethical committee approval. Signed written consent was taken from all subjects before surgery. Including criteria were patient aged between 15 to 55 years old with ASA Ι, ΙΙ (American Society Anesthesiologist) that candidated for elective surgery, such as bowel obstruction, hernia, laparatomy , during 1390 to 5th Azar educational hospital in Gorgan, northeast of Iran.

Alcohol consumption or taking any pain medication during 24 hours before surgery, a history of neurological disease, chronic pain syndrome, thrombofelebit, advanced systemic disease (such as advanced diabetes), and any contraindication based on injection of Propofol led to patient withdrawal from the study. Measuring patients’ pain using VRS (


Verbal Rating Scale) from zero to three which has been developed by MC Hunter and Crirrick. Detail shown in (table 1). After patient’s entering into the operation room ,a No. 20 cannula were inserted in the biggest vein in no dominate hand. (without injection of a local anesthetic) and was connected to normal saline solution (without start of infusion).


Difference between the two independent proportion formula calculated 24 samples for each group, however, considering five groups in our study, adjusted for sampling (19) was calculated, (

=


= 2*24 = 48 48*5= 245 )

g

assume as the number of groups that 245 samples calculated. To achieve as same power as parametric tests we also used the efficiency power of nonparametric test, so that the sample size was multiplied by inverse 95 percent (20)which finally 260 samples was considered.

Simple randomization allocation method was used to assign patients into five groups, so that five


envelopes which containing the name of drugs was prepared and


one out of five randomly selected for a patient and this approach repeated for all patients. In the first group (53 patients)


2mg/kg of


Propofol type Fresenius One percent (MCT/LCT) was injected. In the second group (50 patients),


2 cc of Lidocaine 1% before use of Propofol was injected . The third group (48 patients),


received


2 ml of normal saline 0.09% before the injection of Propofol .Group IV (54 patients)


50 mg Sodium Thiopental before injection of Propofol type Fresenius was injected. Group V (55 patients) also received 100µg Fentanyl before injection of Propofol. The place of injection is the dorsal vein of the hand. None of the patients received premedication and they were asked about the pain in injection place, 5-10 seconds after injection of 25% of anesthetic induction dose. And it was inscribed in questionnaire and after lessening the level of patients’ consciousness the rest of the anesthetics were injected. Anesthesia method were be same in all patients. The Propofol we wanted to use kept at room temperature (21 centigrade). Patients and the


anesthesia nurse who filled out the questionnaires won’t know about the injected solution. And there is no chance to distinguish the solutions because they had the same color, volume and also the same shape. The first anesthesia nurse prepared the medication and injected by the second anesthesia nurse, the measure of pain and discomfort in hand examined by third anesthesia nurses and the questionnaire filled out by the fourth anesthesia nurse .To determine the relationship between premeditation and a measure of the pain Mann-Whitney and Kruskal- Walis test was used and demographic feature was also compared using ANOVA and Chi Square test with Spss 11.5.

Results

257 out of a total 260 participated patients were analyzed in our study and 3 cases due to lack of condition were exclude. Characteristic of study subject including age, gender, weight and ASA physical status were presented in table2. No statistically significant difference saw in demographic characteristics of all groups and were comparable. (Table 2)(p>0.05)The overall and detailed of pain incidence shown for all groups in (table 3).Pain intensity at propofol injection in lidocaine and thiopental groups was much lower than three other groups especially in severe pain however fentanyl were also better than normal saline combined with propofol and using propofol only. No patient experienced spo2 less than 95% and heart rate lower than 50/min. No complication and adverse effect (eg, pain, allergic reaction, inflammation, edema, wheal ) were observed at the injection location 24 h after surgery. There was no conflict of interest .

Discussion

Pain during propofol injection causes anxiety and can interfere an appropriate anesthesia. Pain during Propofol injection mechanism is not well known yet, But it is suggested that perhaps a direct stimulating effect causes the immediate feeling of pain, or an indirect effect dependent on mediators release lead to begin pain.(15) dilatory pain (after 10 to 20 seconds) results from an indirect effect on the endothelium owing to the release of Cyanogens(21). Fat-soluble causes the increased activity of plasma’s kallikrein-kini system that leads to production of bradykinin. These interactions cause dilation and increased permeability in the peripheral veins, lead to an increase in Aqueous phase of Propofol with the endothelium and free efferent nerve endings between the media and intima of vessel wall and eventually cause pain (22). Finally we can say Propofol is a kind of drugs which stimulate skin, phlegm and inner vein wall(23). Gozal and Freeman (24-26) have debated, confined area size between the endothelium and drug is more influential than absolute drug concentration.

A various method such as temperature(27) dilution(28) concurrent use of drugs(29-31) , give a variety to speed injection(32) has been used to attenuate propofol injection pain but different lidokaine dose and technique mostly use to attenuate for such pain (33)Analgesia results of Lidocaine in pain reduction following Propofol injection is not only because of it’s local analgesia but also it causes the decrease in Propofol Ph, and according to a hypothesis, Ph decrease causes Propofol moving into lipid phase and decrease Propofol in Aqueous phase and therefore lead to decreasing pain.(34, 35). In the present study, injection of Lidocaine before Propofol injection leading reduction in pain that the findings are compatible with other studies (23, 26, 36) but with the exception that their doses which were more than ours. Nevertheless controversy still exists (37) maybe for using higher dose in our study . The effect of Sodium Thiopental in pain reduction was accorded with other studies (8, 35, 38, 39). Fentanyl is also diminishes such pain but not as much as lidocaine and thiopental that is consistent in diminishing pain with others investigations (40-42)

Conclusion

This study finding shows that use of Lidocaine and Sodium Thiopental in comparison with other medications cause more reduction in pain especially in severe pains but lidocaine is more available cheaper than thiopental . Although no significant observed between some groups in pain reduction but pay attention to our founding in frequency of pain suggest using propofol with any premedication even normal saline better than injected propofol alone.

Different premedication admixture with propofol to attenuate pain severity


induced by propofol injection:


a double blind randomized controlled clinical trial

Abstract

Background and Objective

Propofol has widely used due to providing pleasant anesthesia and rapid recovery. However; injection pain is one of the main side effects of a propofol that has remained as an undesirable problem. This study compares the effect of thiopental, lidocaine, fentanyl , normal saline admixture with propofol compared with only propofol on injection pain induced by propofol

Materials and methods

A double blind randomized controlled clinical trial was conducted on 257 patients that were randomly allocated to one of five groups to receive only 2mg/kg of Propofol type Fresenius One percent in group I, 2 cc of Lidocaine 1% in group II, 2 ml of Normal Saline 0.09% in group III, 50 mg Sodium Thiopental in Group IV and Group V were injected 100µg Fentanyl before injection of Propofol. Verbal Rating Scale was used for assessing pain.

Results

A significant decrease in pain severity during injection was achieved in group II (lidocaine ) and IV (Thiopental) compared to other groups. Fentanyl was also effective in reducing moderate pain.

Conclusion:

We found that Thiopental and lidocaine reduce more effectively incidence and pain severity than other groups. It seems that aforementioned drugs bee more appropriate as an alternative method to diminish propofol injection pain than others treatment in this study.

Key Word:


propofol, injection pain, premedication

Introduction

Preoperative care cause satisfaction for patient in recent years(1)Propofol is the drug that has attained popularity which has widely used owing to its fast onset time ,short-acting duration , and trivial adverse effects (2) despite these favorable attributes, the prevalence of injection pain has been reported 68-90% and has been ranked seventh among the 33 undesirable clinical problem in anesthesia(3-6). Injection pain severity was reported 5.6 ± 2.3 by measuring system of Visual Analog Scale , which represents unfavorable pain (7). Up to now, different ways have been studied and recommended to reduce the incidence and pain severity of Propofol injection. Among various methods,


emollient of Propofol (8, 9) and using numerous drugs including Lidocaine (10), Thiopental(11) ,Alfentanil (12) and Gransytron or Ondansetron(13)can be noted. There are different emollients of Propofol in Iran such as Fresenius Propofol 1% which has a side branch of a long triglyceride (LCT) and Lipuro Propofol 1% which has side branches of medium and long triglyceride (MCT/LCT) ,that is assuming that later one is more effective in reducing injection pain(14). Lidocaine as a local anesthetic inhibits the beginning and conduction of nervous impulses by decreasing the penetration of nerve membrane to Na+. It prevents the membrane depolarization, effluence and conduction of potential . It’s systemic absorption is rapid via skin and phlegm (throat, respiratory system) (15).Fentanyl is a drug which usually used as a premedication, because of the rapid and short onset, intense analgesia, Stable cardiovascular hemodynamic as well as less histamine release (16). Thiopental from barbiturate family causes hypotension but has a high ability to protect nerves and control ICP (17). Ondansetron is a modern antiemetic drug which is chosen as the antagonist of Hydroxyl Triptamin type 3. This drug reduces nausea and vomiting and its complications are also very low(18). Different advantages of aforementioned drugs for pain persuaded us to use them to understand that how much they can reduce propofol injection pain and which one is more effective.

Methods:

A double blind randomized controlled clinical trial was performed on 257 patients, after obtaining confirmation from both Golestan University of medical science and 5th Azar hospital ethical committee approval. Signed written consent was taken from all subjects before surgery. Including criteria were patient aged between 15 to 55 years old with ASA Ι, ΙΙ (American Society Anesthesiologist) that candidated for elective surgery, such as bowel obstruction, hernia, laparatomy , during 1390 to 5th Azar educational hospital in Gorgan, northeast of Iran.

Alcohol consumption or taking any pain medication during 24 hours before surgery, a history of neurological disease, chronic pain syndrome, thrombofelebit, advanced systemic disease (such as advanced diabetes), and any contraindication based on injection of Propofol led to patient withdrawal from the study. Measuring patients’ pain using VRS (


Verbal Rating Scale) from zero to three which has been developed by MC Hunter and Crirrick. Detail shown in (table 1). After patient’s entering into the operation room ,a No. 20 cannula were inserted in the biggest vein in no dominate hand. (without injection of a local anesthetic) and was connected to normal saline solution (without start of infusion).


Difference between the two independent proportion formula calculated 24 samples for each group, however, considering five groups in our study, adjusted for sampling (19) was calculated, (

=


= 2*24 = 48 48*5= 245 )

g

assume as the number of groups that 245 samples calculated. To achieve as same power as parametric tests we also used the efficiency power of nonparametric test, so that the sample size was multiplied by inverse 95 percent (20)which finally 260 samples was considered.

Simple randomization allocation method was used to assign patients into five groups, so that five


envelopes which containing the name of drugs was prepared and


one out of five randomly selected for a patient and this approach repeated for all patients. In the first group (53 patients)


2mg/kg of


Propofol type Fresenius One percent (MCT/LCT) was injected. In the second group (50 patients),


2 cc of Lidocaine 1% before use of Propofol was injected . The third group (48 patients),


received


2 ml of normal saline 0.09% before the injection of Propofol .Group IV (54 patients)


50 mg Sodium Thiopental before injection of Propofol type Fresenius was injected. Group V (55 patients) also received 100µg Fentanyl before injection of Propofol. The place of injection is the dorsal vein of the hand. None of the patients received premedication and they were asked about the pain in injection place, 5-10 seconds after injection of 25% of anesthetic induction dose. And it was inscribed in questionnaire and after lessening the level of patients’ consciousness the rest of the anesthetics were injected. Anesthesia method were be same in all patients. The Propofol we wanted to use kept at room temperature (21 centigrade). Patients and the


anesthesia nurse who filled out the questionnaires won’t know about the injected solution. And there is no chance to distinguish the solutions because they had the same color, volume and also the same shape. The first anesthesia nurse prepared the medication and injected by the second anesthesia nurse, the measure of pain and discomfort in hand examined by third anesthesia nurses and the questionnaire filled out by the fourth anesthesia nurse .To determine the relationship between premeditation and a measure of the pain Mann-Whitney and Kruskal- Walis test was used and demographic feature was also compared using ANOVA and Chi Square test with Spss 11.5.

Results

257 out of a total 260 participated patients were analyzed in our study and 3 cases due to lack of condition were exclude. Characteristic of study subject including age, gender, weight and ASA physical status were presented in table2. No statistically significant difference saw in demographic characteristics of all groups and were comparable. (Table 2)(p>0.05)The overall and detailed of pain incidence shown for all groups in (table 3).Pain intensity at propofol injection in lidocaine and thiopental groups was much lower than three other groups especially in severe pain however fentanyl were also better than normal saline combined with propofol and using propofol only. No patient experienced spo2 less than 95% and heart rate lower than 50/min. No complication and adverse effect (eg, pain, allergic reaction, inflammation, edema, wheal ) were observed at the injection location 24 h after surgery. There was no conflict of interest .

Discussion

Pain during propofol injection causes anxiety and can interfere an appropriate anesthesia. Pain during Propofol injection mechanism is not well known yet, But it is suggested that perhaps a direct stimulating effect causes the immediate feeling of pain, or an indirect effect dependent on mediators release lead to begin pain.(15) dilatory pain (after 10 to 20 seconds) results from an indirect effect on the endothelium owing to the release of Cyanogens(21). Fat-soluble causes the increased activity of plasma’s kallikrein-kini system that leads to production of bradykinin. These interactions cause dilation and increased permeability in the peripheral veins, lead to an increase in Aqueous phase of Propofol with the endothelium and free efferent nerve endings between the media and intima of vessel wall and eventually cause pain (22). Finally we can say Propofol is a kind of drugs which stimulate skin, phlegm and inner vein wall(23). Gozal and Freeman (24-26) have debated, confined area size between the endothelium and drug is more influential than absolute drug concentration.

A various method such as temperature(27) dilution(28) concurrent use of drugs(29-31) , give a variety to speed injection(32) has been used to attenuate propofol injection pain but different lidokaine dose and technique mostly use to attenuate for such pain (33)Analgesia results of Lidocaine in pain reduction following Propofol injection is not only because of it’s local analgesia but also it causes the decrease in Propofol Ph, and according to a hypothesis, Ph decrease causes Propofol moving into lipid phase and decrease Propofol in Aqueous phase and therefore lead to decreasing pain.(34, 35). In the present study, injection of Lidocaine before Propofol injection leading reduction in pain that the findings are compatible with other studies (23, 26, 36) but with the exception that their doses which were more than ours. Nevertheless controversy still exists (37) maybe for using higher dose in our study . The effect of Sodium Thiopental in pain reduction was accorded with other studies (8, 35, 38, 39). Fentanyl is also diminishes such pain but not as much as lidocaine and thiopental that is consistent in diminishing pain with others investigations (40-42)

Conclusion

This study finding shows that use of Lidocaine and Sodium Thiopental in comparison with other medications cause more reduction in pain especially in severe pains but lidocaine is more available cheaper than thiopental . Although no significant observed between some groups in pain reduction but pay attention to our founding in frequency of pain suggest using propofol with any premedication even normal saline better than injected propofol alone.