Propofol-induced Pain Research Articles

Mechanism of action of metoprolol in reducing propofol-induced pain

Mechanism of action of metoprolol in reducing propofol-induced pain

Effect of Nitrous Oxide in Reducing Pain of Propofol Injection in Adult Patients

In a randomized, double-blind, prospective trial we compared the efficacy of pre-treatment with nitrous oxide (with or without premixed lignocaine in propofol) for the prevention of propofol-induced pain. Ninety consecutive patients were recruited in the study and divided into three groups of 30 each, who received either 50% nitrous oxide in oxygen along with lignocaine 40 mg mixed in 1% propofol 20 ml (Group NL), 50% nitrous oxide in oxygen without lignocaine in propofol (Group N), and 50% oxygen in air with lignocaine mixed in propofol 40 mg (Group L). Pain scores were graded on a four point verbal rating scale (0-3). Eighty-nine patients completed the study while one patient developed excitement, agitation and tremor during nitrous oxide in oxygen inhalation. Eleven patients (36.7%) complained of pain in the group L compared to 7 (23.3%), and 1 (3.3%), in groups N and NL respectively [group NL vs group L (P < 0.001) and group NL vs N (P < 0.001)]. There was no statistical difference observed between group N and group L. Inhalation of 50% nitrous oxide reduces pain on propofol injection. The combination of 50% nitrous oxide and lignocaine mixed with propofol was the most effective treatment.

Ketamine pretreatment with venous occlusion attenuates pain on injection with propofol

Ketamine pretreatment with venous occlusion attenuates pain on injection with propofol

The Effect of Lidocaine on Propofol-induced Hemodynamic Changes during Induction of Anesthesia in Elderly Patients

Background: Propofol has a high incidence of pain when administered by intravenous injection. Among the many different methods available, lidocaine is used most frequently to minimize this pain. Propofol also has a depressant action on hemodynamics, especially in the elderly. The present study was aimed to examine whether lidocaine affects hemodynamic changes associated with propofol injection and endotracheal intubation, and whether it attenuates propofol-induced pain. Methods: Eighty patients, over 60 years old, ASA physical status I and II, were randomly divided into four groups of 20 each according to lidocaine dosage mixed with 2 mg/kg of propofol given over 30 seconds during the induction of anesthesia; 0 mg (control group), 20 mg, 40 mg and 80 mg. Mean arterial blood pressure (MAP), heart rate (HR), and bispectral index scale (BIS) were measured before anesthetic induction (baseline value), 1 minute after the start of induction, immediately before endotracheal intubation, and then every minute for 5 minutes. Injection pain was scored as none, mild, moderate, or severe. Results: MAP decreased significantly following the propofol injection and then increased after endotracheal intubation in all four groups, the magnitude of this decrease did not differ among the groups. HR increased after the propofol injection and then decreased. It increased again after intubation in all four groups. BIS was decreased by the induction of anesthesia, but was not affected by endotracheal intubation in any group. The three lidocaine groups had a lower incidence and severity of propofol-induced pain than the control group, and the effect were comparable among the lidocaine-treated groups. Conclusions: Our results indicate that lidocaine 20, 40 or 80 mg mixed with propofol does not affect the hemodynamic changes associated with propofol and endotracheal intubation, but that they similarly attenuate the injection pain associated with propofol.

Efficacy of Lignocaine plus Ketamine at Different Doses in the Prevention of Pain Due to Propofol Injection

Pain on injection is still a major problem with propofol. Lignocaine (lidocaine) is effective in preventing propofol-induced pain on injection, but cannot entirely control the pain. The purpose of this study was to examine the effect of lignocaine plus ketamine, an N-methyl-D-aspartate receptor antagonist, on pain on injection of propofol. Prospective, randomised, double-blind, placebo-controlled study. University Hospital. 120 female patients scheduled for gynaecological laparoscopy. Patients received intravenously lignocaine 20mg plus either placebo (saline) or ketamine at three different doses (2.5mg, 5mg and 10mg), with manual venous occlusion for 1 minute, followed by administration of propofol 0.5 mg/kg into a dorsal hand vein (n = 30 in each group). A blinded researcher asked the patients to assess pain during the propofol injection. MAIN OUTCOMES MEASURES AND RESULTS: Twelve of 30 patients (40%) complained of pain in the lignocaine/placebo group compared with three (10%) in the lignocaine/ketamine 5mg group and three (10%) in the lignocaine/ketamine 10mg group (both p = 0.015). No significant differences were found between the lignocaine/ketamine 2.5mg (10 patients [33%]) and lignocaine/placebo groups. No complications such as pain, oedema, wheal or flare response were observed at injection sites within the first 24 hours after anaesthesia. Combined lignocaine 20mg and ketamine 5mg, with manual venous occlusion, is more effective than lignocaine 20mg alone for pain control during propofol injection.

Pain during Injection of Propofol: The Effect of Prior Administration of Ephedrine

Propofol causes pain on intravenous injection in 28 to 90% of patients. A number of techniques have been tried to minimize propofol-induced pain, with variable results. In a randomized, double-blind, placebo-controlled trial, we compared the efficacy of ephedrine 30 microg/kg pretreatment to lignocaine 40 mg for prevention of propofol-induced pain. Ninety-three adult patients, ASA 1 and 2, undergoing elective laparoscopic cholecystectomy were randomly assigned to three groups of 31 each. Group 1 received normal saline, group 2 received lignocaine 2% (40 mg) and group 3 received 30 microg/kg ephedrine. All pretreatment drugs were made up to 2 ml. Pain at the time of propofol injection was assessed on a four-point scale: 0=no pain, 1 =mild pain, 2=moderate pain, and 3=severe pain. Twenty-seven patients (87%) of ephedrine pretreatment patients had pain during intravenous injection of propofol as compared to 24 (77%) in the normal saline group. In the lignocaine group, propofol-induced pain was observed in only 13 (42%) when compared with other study groups (P<0.05). Pretreatment with ephedrine 30 microg/kg did not attenuate pain associated with intravenous injection of propofol, nor did it improve haemodynamic stability during induction. However, pretreatment with 2% lignocaine (40 mg) was effective in attenuating propofol-associated pain.

Reduction of Propofol-Induced Pain through Pretreatment with Lidocaine and/or Flurbiprofen

Pain is a well recognised complication of propofol injection. The purpose of this study was to compare the efficacy of flurbiprofen, lidocaine and a combination of the two in reducing pain on injection of propofol. Prospective, randomised, double-blind, placebo-controlled study. University hospital in Tsukuba City, Japan. 120 patients, 56 males and 64 females, aged 20-66 years, scheduled for elective plastic surgery were included. Patients received intravenously either lidocaine 20mg, flurbiprofen 50mg, both, or placebo (saline) accompanied by manual venous occlusion for 2 minutes, followed by administration of propofol 2 mg/kg into a dorsal hand vein (n = 30 in each group). A blinded researcher asked each patient to evaluate the pain score (0 = none, 1 = mild, 2 = moderate, 3 = severe) during propofol injection. The incidence and intensity of pain was less in patients receiving lidocaine (27%, pain score 0 [median]), flurbiprofen (43%, 0), or both (3%, 0) along with venous occlusion than in those receiving placebo (90%, 2) along with venous occlusion (p < 0.01). Combined lidocaine and flurbiprofen with venous occlusion was the most effective treatment (p < 0.05). No complications such as pain, oedema, wheal or flare response were observed at the injection sites within the first 24 hours after surgery. Combined lidocaine 20mg and flurbiprofen 50mg along with venous occlusion for 2 minutes was very effective for reducing pain on injection of propofol in patients scheduled for elective plastic surgery.

Profound Pain Due to Propofol Injection Triggered Myocardial Ischemia in a Patient with a Suspected Pheochromocytoma

To the Editor: Propofol-induced pain is one of side effects observed during injection (1). However, to our knowledge, there are no reports of serious accidents associated with propofol-induced pain. We describe a patient who had a suspected pheochromocytoma and developed myocardial ischemia triggered by propofol-induced pain during induction of anesthesia. The patient, a 52-year-old man (height, 165 cm; weight, 55 kg), was scheduled for a laparoscopic adrenalectomy for a suspected pheochromocytoma detected by CT scan at health screening. Preoperative examinations revealed slight increases in plasma catecholamines and 24-hour urinary catecholamines excretion. Preparation involved a period of preoperative α-blockade with prazosin hydrochloride. Before induction, the patient’s hemoglobin was 13.3 g/dL, the electrocardiogram (ECG) findings were within normal limits, baseline heart rate was 65 bpm, and arterial blood pressure was 95/55 mm Hg. Under continuous monitoring of blood pressure through a radial artery catheter, general anesthesia was induced by IV administration of propofol (100 mg/30 s) through the 18-gauge catheter at his forearm. The patient complained of a profound vascular pain during the infusion of propofol. After loss of consciousness, arterial blood pressure increased to 230/130 mm Hg and a sinus tachycardia (130 bpm) was observed. Immediately, 0.5 mg nicardipine and 50 mg propofol combined with inhalation of 2% sevoflurane were administered and his blood pressure normalized. The trachea was intubated after adequate muscle relaxation was attained and simultaneously the ECG in lead II showed an elevation of the ST segment (Fig. 1), then arterial blood pressure decreased to 80/50 mm Hg. After intravenous 0.1-mg phenylephrine and continuous infusion of nitroglycerin (0.5 μg/kg/min), diltiazem (1 μg/kg/min), and dopamine (3 μg/kg/min) were infused, the ST segment returned to normal in 10 min and his blood pressure improved to 110/55 mm Hg. The coronary angiography performed a week later revealed normal coronary arteries. We speculated that propofol-induced pain could cause a sudden increase in plasma catecholamine levels derived from a pheochromocytoma and eventually develop myocardial ischemia. Propofol should be used carefully in such patients.Figure 1: (A) Electrocardiogram recorded before the induction of anesthesia. It revealed a normal sinus rhythm. (B) Immediately after induction of anesthesia, elevation of the ST segment was noted but it normalized in 10 minutes after treatment of hypotension and myocardial ischemia.Tetsuro Morishima, MD Kazuya Sobue, MD, PhD Hajime Arima, MD Sayuki Tanaka, MD MinHye So, MD Hiroshi Ando, MD, PhD Hirotada Katsuya, MD, PhD

Effect of Local Warming of the Injection Site and Forearm on Propofol-Induced Pain

Background: Propofol often causes pain when injected into small peripheral veins, but the pain can be minimized by using a larger vein. This study was designed to determine whether local warming of the injection site and forearm before propofol injection is effective in reducing pain. Methods: Sixty adult patients undergoing general anesthesia for an elective surgery were randomly allocated to one of two groups. All were unpremedicated and had an 18-gauge cannula inserted into a cephalic vein on the wrist. Patients in group 1 (n = 30) received 1% propofol at room temperature. Patients in group 2 (n = 30) received 1% propofol after local warming (36-37oC) of the injection site and forearm using a forced-air warming system (Bair Hugger). For each patient, the pain during injection of the propofol solution was graded as none, mild, moderate, or severe. Results: Overall the incidence of pain was significantly reduced in group 2 (36.7%) compared with group 1 (66.7%). No patients complained of pain at the injection site and forearm in group 2. However, there was no significant difference in the incidence or severity of pain on the elbow and axilla between the two groups. Conclusions: We found that local warming applied to the injection site (wrist) and forearm before propofol injection is significantly effective in reducing pain at the injection site and forearm, but there was no improvement of pain on the elbow and axilla when injecting.

Effect of Orally Administered Clonidine on Pain during Injection of Propofol

Background: Several interventions have been investigated to prevent pain on intravenous injection of propofol. Clonidine as an alpha-2 agonist is recognized to be an effective analgesic. Therefore, oral premedication of clonidine has been explored in relation to pain responses to propofol injection. Methods: In a randomized, double blind study, 82 ASA I-II patients were allocated to one of two groups: oral clonidine (2.5/kg) 60-90 min before the induction with propofol and lidocaine 40 mg followed by intravenous propofol. The pain score in the groups was assessed as follows: 0 = no pain, 1 = minimal pain, 2 = moderate pain, 3 = severe pain. Results: Nine patients in the lidocaine-pretreated group and 16 patients in the clonidine group experienced pain. In cases of injection site was in hand, the incidence of pain was 9/15 patients in the lidocaine group and 12/15 patients in the clonidine group, respectively; however, none/26 patients in the lidocaine group and 4/26 patients in the clonidine group in a forearm vein, respectively. There were no significant differences between the groups in terms of pain score regardless the injection sites. Oral clonidine also attenuated hemodynamic responses to a laryngoscopy and intubation. Conclusions: Oral premedication of clonidine 2.5/kg revealed a comparable analgesic effect with intravenous lidocaine 40 mg on propofol-induced pain.

A potential mechanism of propofol-induced pain on injection based on studies using nafamostat mesilate

To elucidate the mechanism of propofol-induced pain on injection, we performed several studies using nafamostat mesilate, a kallikrein inhibitor, or lidocaine. As both pretreatment and low-dose mixing with nafamostat produced the same effects on pain reduction, we used the latter method in the following experiments. Low-dose mixing had the same effect on injection pain as mixing with lidocaine. The extent of pain was assessed by measuring bradykinin concentrations by mixing with blood. Propofol and its lipid solvent mixed with blood produced approximately two-fold generation of bradykinin compared with the saline control, and this was inhibited completely by nafamostat and lidocaine. Injection of the lipid solvent before propofol significantly aggravated pain compared with prior injection of saline, although the lipid solvent injected twice caused no change in pain. These results suggest that the lipid solvent for propofol activates the plasma kallikrein-kinin system and produces bradykinin which modifies the injected local vein. This modification of the peripheral vein may increase the contact between the aqueous phase propofol and the free nerve endings of the vessel, resulting in aggravation of propofol-induced pain.

Acidified propofol retains its anaesthetic potency after storage.

The reduction in propofol-induced pain on injection caused by the addition of lignocaine results mainly from a drop in pH, which reduces the concentration of propofol in the aqueous phase of the emulsion. It is not an effect of the local anaesthetic per se. Propofol emulsion mixed with lignocaine destabilizes within hours. We mixed 10 parts of propofol 1% emulsion with one part of 0.0064 M HCl or 0.013 M HCl, respectively. These mixtures were stored for 3 months and compared with a freshly prepared solution of propofol 1% emulsion and saline, in the same proportion, regarding their ability to induce anaesthesia in the rat. There was no significant difference in the amount of propofol required to induce anaesthesia, nor was there any difference in recovery time between the three groups.

Acidified propofol retains its anaesthetic potency after storage

The reduction in propofol-induced pain on injection caused by the addition of lignocaine results mainly from a drop in pH, which reduces the concentration of propofol in the aqueous phase of the emulsion. It is not an effect of the local anaesthetic per se. Propofol emulsion mixed with lignocaine destabilizes within hours. We mixed 10 parts of propofol 1% emulsion with one part of 0.0064 M HCl or 0.013 M HCl, respectively. These mixtures were stored for 3 months and compared with a freshly prepared solution of propofol 1% emulsion and saline, in the same proportion, regarding their ability to induce anaesthesia in the rat. There was no significant difference in the amount of propofol required to induce anaesthesia, nor was there any difference in recovery time between the three groups.

The Effect of 30 Min Pre-treatment with Continuous Lidocaine Infusion on Propofol-induced Pain

The Effect of 30 Min Pre-treatment with Continuous Lidocaine Infusion on Propofol-induced Pain

Effects of Topical Nitroglycerin and Intravenous Lidocaine on Propofol-Induced Pain on Injection

O'HARA, JEROME F. JR.; SPRUNG, JURAJ; LASETER, JEFFREY T.; MAURER, WALTER G.; CARPENTER, THOMAS; BEVEN, MICHAEL; MASCHA, E D; Zarmsky, Roxanne M.D. Author Information

Effect of Lignocaine and pH on Propofol-Induced Pain

Effect of Lignocaine and pH on Propofol-Induced Pain

Does Lidocaine Mixture for Preventing The Pain on Propofol Injection Affect Anesthetic Induction and Hemodynamic Responses to Tracheal Intubation

Background: We hypothesized that intravenous lidocaine mixed with propofol may have an influence on anesthesia induction and hemodynamic responses to propofol induction and endotracheal intubation as well as propofol-induced pain on injection. Methods: Seventy-five patients were allocated to group L1 (2% lidocaine 1.5 mg/kg, n=25), group L2 (2% lidocaine 2 mg/kg, n=25) or group C (normal saline 0.05 mL/kg, n=25) according to the lidocaine dosage mixed with propofol 2 mg/kg. The pain on injection was scored as none, mild, moderate, and severe. The site of pain and recall of pain were also recorded. Loss of verbal response was observed during induction. Mean arterial blood pressure (MAP) and heart rate (HR) were recorded before anesthetic induction (baseline value), immediately before and after endotracheal intubation, and every min until 5 min thereafter. Results: Ninety-two percent of patients reported pain upon injection in group C, whereas 8% of the patients in group L1 and no patient in group L2. Loss of verbal response before injection of total dose of propofol was observed in 44% in group L2, 36% in group L1 and 28% in group C. Lowered MAP caused by propofol increased significantly after endotracheal intubation in all three groups (p＜0.05). HR increased immediately and 1 min after endotracheal intubation in all three groups (p＜0.05). Conclusions: Our results indicate that intravenous lidocaine 1.5 mg/kg or 2 mg/kg mixed with propofol 2 mg/kg significantly reduces the incidence and the degree of pain, but does not affect anesthesia induction and hemodynamic responses to propofol and tracheal intubation. (Korean J Anesthesiol 1998; 35: 883∼889)

Effect of lignocaine and pH on propofol-induced pain

Propofol has the disadvantage of pain on injection. A higher partition of propofol in the aqueous phase of the preparation causes a higher incidence of pain on injection while addition of 1% lignocaine to propofol reduces pain. The low concentration of this local anaesthetic and the rapid pain relief observed indicates that mechanisms other than local anaesthesia are involved, that is change in pH. We performed a clinical study to investigate the influence of lignocaine and pH on pain during injection of 1% Diprivan. Ten parts of 1% Diprivan were mixed with one part of saline, 1% lignocaine or hydrochloric acid to achieve the same pH as that after addition of lignocaine. Diprivan 1% mixed with 1% lignocaine and with hydrochloric acid gave mean pain ratings (1-10) of 0.32 (SD 0.75) (n = 25) and 0.88 (1.30) (n = 24), respectively. These ratings were significantly lower than ratings after injection of a saline-Diprivan mixture (2.18 (2.06), n = 22). The pH of the 1% Diprivan formulation decreased after mixing with 1% lignocaine. The concentration of propofol in the aqueous phase was lower when 1% Diprivan was mixed with 1% lignocaine (0.376 g litre-1) or HCl (0.392 g litre-1) compared with 1% Diprivan and saline (0.476 g litre-1) mixed in the same proportion. Thus pH changes may modify propofol-induced pain on injection by a mechanism different from the effect of the local anaesthetic on the vascular endothelium. Our findings may explain why lignocaine mixed with propofol causes less pain than injection of lignocaine followed by propofol.

Effects of Topical Nitroglycerin and Intravenous Lidocaine on Propofol-Induced Pain on Injection

We performed a randomized, placebo-controlled, double-blind study to compare the efficacy of intravenous (I.V.) lidocaine and topical nitroglycerin ointment in preventing pain during propofol injection. Nitroglycerin or placebo ointments were applied to the back of the hand over the skin area overlying the I.V. catheter tip; lidocaine was or was not added to the propofol solution. One hundred twenty-four patients were randomly assigned to receive one of four treatments: placebo and plain propofol, propofol mixed with lidocaine, nitroglycerin ointment and plain propofol, and nitroglycerin ointment and propofol mixed with lidocaine. Hence, there were 31 patients in each treatment group. Patients receiving nitroglycerin ointment and plain propofol had the highest incidence of pain on propofol injection (23 of 31 patients, 74%), and the highest median pain score. Only when lidocaine was added to propofol did it effectively reduce the incidence and severity of pain. Patients aged 50 yr and older had a significantly lower incidence and less severe pain. We conclude that lidocaine and age, but not topical nitroglycerin ointment, are factors associated with a decreased incidence of propofol-induced pain.

Effects of Topical Nitroglycerin and Intravenous Lidocaine on Propofol-Induced Pain on Injection

We performed a randomized, placebo-controlled, double-blind study to compare the efficacy of intravenous (IV) lidocaine and topical nitroglycerin ointment in preventing pain during propofol injection. Nitroglycerin or placebo ointments were applied to the back of the hand over the skin area overlying the IV catheter tip; lidocaine was or was not added to the propofol solution. One hundred twenty-four patients were randomly assigned to receive one of four treatments: placebo and plain propofol, propofol mixed with lidocaine, nitroglycerin ointment and plain propofol, and nitroglycerin ointment and propofol mixed with lidocaine. Hence, there were 31 patients in each treatment group. Patients receiving nitroglycerin ointment and plain propofol had the highest incidence of pain on propofol injection (23 of 31 patients, 74%), and the highest median pain score. Only when lidocaine was added to propofol did it effectively reduce the incidence and severity of pain. Patients aged 50 yr and older had a significantly lower incidence and less severe pain. We conclude that lidocaine and age, but not topical nitroglycerin ointment, are factors associated with a decreased incidence of propofol-induced pain. (Anesth Analg 1997;84:865-9)