Anaesthesia, 1990, Volume 45, pages 4 4 3 4 4 4
Pain on injection of propofol: the effect of injectate temperature
A. McCRIRRICK
AND
S. HUNTER
Summary A double-blind, randomised clinical study was undertaken to compare the efSect of temperature on the incidence and severity of the pain experienced on injection of propofol. The number of patients who experienced pain and the severity of the pain were reduced signijicantly when propofol was administered at a temperature of 4°C. The eficacy of propofol as an induction agent appeared to remain unaltered.
Key words Anaesthetics, intravenous; propofol. Complications; pain.
It is well recognised that propofol may cause pain or discomfort on injection when administered intravenously, especially into a vein on the dorsum of the hand. Studies have shown that the incidence may be as high as 45%.' Premedication has little influence on the incidence of pain but may reduce its severity.2 Other important factors are known to be the site and speed of injection3-' and the use of analgesics and local anaesthetics in combination with p r o p o f ~ l . ~This - ~ study was designed to assess whether the temperature of propofol affects the incidence or severity of pain on injection.
Patients and methods The study was performed on 71 adult patients of ASA class 1 and weight 50-85 kg who presented for minor, elective surgery. Informed consent was obtained. All patients received lorazepam 0.5 mg/lO kg to a maximum of 4 mg, 90 minutes before surgery. A 22-gauge cannula was inserted into the largest apparent vein in the dorsum of the hand. The patients were then allocated randomly to one of two groups. General anaesthesia was induced with intravenous propofol 2.5 mg/kg. Patients in group 1 received propofol that had been taken directly from the refrigerator (45°C). Those in group 2 received propofol maintained at room temperature (20-23°C). The speed of injection was controlled carefully. One quarter of the total calculated
dose was given over the first 5 seconds; after this period, the injection was stopped for 5 seconds to allow assessment of discomfort by the method outlined below. An initial pain score was obtained. Induction was then continued and the second quarter of the total induction dose was administered over a further 5-second period. The patient was questioned again and a second pain score obtained. Finally, the remainder of the induction dose was administered. The level of pain was assessed by a second, independent anaesthetist who was unaware of the group to which the patient had been allocated. The pain score was obtained by asking the patient a standard question about the comfort of the injection and the verbal response, together with behavioural signs such as facial grimacing, arm withdrawal or tears. A score of 0 to 3, which corresponded to no pain, mild, moderate and severe pain, respectively, was recorded (Table 1). Results The second pain score was higher in all cases and this score was used for later analysis. The results are shown in Table 2. The overall incidence of pain in group 2 was 46% compared with 23% in group 1 (p < 0.05). In addition, less patients in group 1 experienced severe pain (3% versus 21 Yo;p < 0.025). Propofol induced anaesthesia successfully irrespective of temperature.
A. McCrirrick, BM, FCAnaes, RAF, Registrar, S. Hunter, BSc, MB, BS, FFARCS, RAF, Consultant, Anaesthetic Department, Princess Alexandra Hospital, Royal Air Force Wroughton, Swindon, Wiltshire SN4 OQJ. Accepted 10 November 1989. 0003-2409/90/060443
+02 $03.00/0
@ 1990 The Association of Anaesthetists of Gt Britain and Ireland 443
A . McCrirrick and S . Hunter
444
Table 1. Assessment of pain.
Pain score
Degree of pain
Rcsponse
0
None
I
Mild
Negative response to questioning. Pain reported in response to questioning only, without any behavioural signs. Pain reported in response to questioning and accompanied by a behavioural sign, or pain reported spontaneously without questioning. Strong vocal response or response accompanied by facial grimacing, arm withdrawal or tears.
2
3
Moderate
Severe
Discussion The incidence of pain associated with injection of propofol at room temperature in this study was 46% which is similar to that in previous studies.’ Our results indicate that propofol injected a t a temperature of 4 5 ° C is associated with a reduced incidence of pain o n injection. Previous investigators have shown that the injection of propofol into a vein in the antecubital fossa is associated with a low incidence of pain.‘-7 However, this route is seldom used in clinical anaesthetic practice as the dorsum of the hand is more convenient and accessible during surgery. Brooker e t aL9 showed that freshly mixed propofol and 1% lignocaine reduced the incidence of pain o n injection significantly. Other workers have shown that the addition of lignocaine may reduce the overall incidence of pain on injection into the dorsum of the hand t o less than 9%.’-* These studies may not be directly comparable to ours because of the variations in premedication and the use of pre-induction opioids in some cases. The datasheet supplied by ICI Pharmaceuticals recommends that propofol should be stored a t room temperature; however, direct communication with the company has confirmed that propofol may be stored and administered a t any temperature below 25°C provided that it is not frozen. The exact mechanism for the production of pain with propofol injection remains to be elucidated. Some authors have implicated a kinin c a ~ c a d e ,which ~ would result in a slight delay before pain is experienced. The second pain score in our study was always higher than the first if pain was experienced. The indirect biochemical cascade mechanism may be supported by our findings, in that biochemical
Table 2. Pain assessments after administration of propofol at a temperature of 4 5 ° C (group 1) or at room temperature (group 2). 0 No pain
Mild
2 Moderate
3 Severe
Group 1 n = 34 Group 2
26
3
4
1
n = 37
20
4
5
8
1
Significant difference between column 0 and columns I + 2 + 3 (overall incidence of pain) p < 0.05 (chi-squared test).
reactions might be expected to occur less vigorously a t lower temperatures, and may fail t o reach pain threshold levels in some patients. In conclusion, it appears that the use of propofol a t 45°C may provide a simple and safe method of reducing the incidence of pain o n injection without the addition of other pharmacological agents.
References I . UPPINGTON J, KAYNH, SEARJW. Propofol (‘Diprivan‘)as a supplement to nitrous oxide-oxygen for the maintenance of anaesthesia. Postgraduate Medical Journal 1985; 61 (Suppl. 3): 8&3. 2. BILAINEJ, DESMONTS JM. Effects of premedication with atropine or hydroxyzine on induction and maintenance of anaesthesia with propofol (‘Diprivan’). Postgraduate Medical Journal 1985; 61 (Suppl. 3): 38-9. 3. BRICCS LP, WHITEM. The effects of premedicdtion on anaesthesia with propofol (‘Diprivan’). Postgraduate Medical Journal 1985: 61 (Suppl. 3): 35-7. 4. KNELL PJW, MCKEAN JF. An investigation of the pharmacokinetic profile of propofol (‘Diprivan’) after administration for induction and maintenance of anaesthesia by repeat bolus doses in patients having spinal anaesthetic block. Postgraduate Medical Journal 1985; 61 (Suppl. 3): 60-1. 5. LEESNW, MCCULLOCH M, MAIRWB. Propofol (‘Diprivan’) for induction and maintenance of anaesthesia. Postgraduate Medical Journal 1985; 61 (Suppl. 3): 88-9. 6. STARK RD, BINKSSM, DUTKA VN, OCONNOR K M , AKNSTEIN MJA, GLENJB. A review of the safety and tolerance of propofol (‘Diprivan’). Postgraduate Medical Journal 1985; 61 (SUPPI.3): 152-6. 7. SCOTTRPF, SAUNDERS DA, NORMAN J. Propofol: clinical strategies for preventing the pain of injection. Anaesthesia 1988; 43: 4924. 8. HELBO-HANSEN S, WESTERCARKD V, KROCHBL, SWENDSEN HP. The reduction of pain on injection of propofol; the effects of the addition of lignocaine. Acta Anaesthesiologica Scandinavica 1988; 32: 5 0 2 4 . 9. BKOOKEKJ, HULLCJ, STAFFORD M. Effects of lignocaine on pain caused by propofol injection. Anaesthesia 1985; 4 0 91-2.
Pain on injection of propofol: the effect of injectate temperature
A. McCRIRRICK
AND
S. HUNTER
Summary A double-blind, randomised clinical study was undertaken to compare the efSect of temperature on the incidence and severity of the pain experienced on injection of propofol. The number of patients who experienced pain and the severity of the pain were reduced signijicantly when propofol was administered at a temperature of 4°C. The eficacy of propofol as an induction agent appeared to remain unaltered.
Key words Anaesthetics, intravenous; propofol. Complications; pain.
It is well recognised that propofol may cause pain or discomfort on injection when administered intravenously, especially into a vein on the dorsum of the hand. Studies have shown that the incidence may be as high as 45%.' Premedication has little influence on the incidence of pain but may reduce its severity.2 Other important factors are known to be the site and speed of injection3-' and the use of analgesics and local anaesthetics in combination with p r o p o f ~ l . ~This - ~ study was designed to assess whether the temperature of propofol affects the incidence or severity of pain on injection.
Patients and methods The study was performed on 71 adult patients of ASA class 1 and weight 50-85 kg who presented for minor, elective surgery. Informed consent was obtained. All patients received lorazepam 0.5 mg/lO kg to a maximum of 4 mg, 90 minutes before surgery. A 22-gauge cannula was inserted into the largest apparent vein in the dorsum of the hand. The patients were then allocated randomly to one of two groups. General anaesthesia was induced with intravenous propofol 2.5 mg/kg. Patients in group 1 received propofol that had been taken directly from the refrigerator (45°C). Those in group 2 received propofol maintained at room temperature (20-23°C). The speed of injection was controlled carefully. One quarter of the total calculated
dose was given over the first 5 seconds; after this period, the injection was stopped for 5 seconds to allow assessment of discomfort by the method outlined below. An initial pain score was obtained. Induction was then continued and the second quarter of the total induction dose was administered over a further 5-second period. The patient was questioned again and a second pain score obtained. Finally, the remainder of the induction dose was administered. The level of pain was assessed by a second, independent anaesthetist who was unaware of the group to which the patient had been allocated. The pain score was obtained by asking the patient a standard question about the comfort of the injection and the verbal response, together with behavioural signs such as facial grimacing, arm withdrawal or tears. A score of 0 to 3, which corresponded to no pain, mild, moderate and severe pain, respectively, was recorded (Table 1). Results The second pain score was higher in all cases and this score was used for later analysis. The results are shown in Table 2. The overall incidence of pain in group 2 was 46% compared with 23% in group 1 (p < 0.05). In addition, less patients in group 1 experienced severe pain (3% versus 21 Yo;p < 0.025). Propofol induced anaesthesia successfully irrespective of temperature.
A. McCrirrick, BM, FCAnaes, RAF, Registrar, S. Hunter, BSc, MB, BS, FFARCS, RAF, Consultant, Anaesthetic Department, Princess Alexandra Hospital, Royal Air Force Wroughton, Swindon, Wiltshire SN4 OQJ. Accepted 10 November 1989. 0003-2409/90/060443
+02 $03.00/0
@ 1990 The Association of Anaesthetists of Gt Britain and Ireland 443
A . McCrirrick and S . Hunter
444
Table 1. Assessment of pain.
Pain score
Degree of pain
Rcsponse
0
None
I
Mild
Negative response to questioning. Pain reported in response to questioning only, without any behavioural signs. Pain reported in response to questioning and accompanied by a behavioural sign, or pain reported spontaneously without questioning. Strong vocal response or response accompanied by facial grimacing, arm withdrawal or tears.
2
3
Moderate
Severe
Discussion The incidence of pain associated with injection of propofol at room temperature in this study was 46% which is similar to that in previous studies.’ Our results indicate that propofol injected a t a temperature of 4 5 ° C is associated with a reduced incidence of pain o n injection. Previous investigators have shown that the injection of propofol into a vein in the antecubital fossa is associated with a low incidence of pain.‘-7 However, this route is seldom used in clinical anaesthetic practice as the dorsum of the hand is more convenient and accessible during surgery. Brooker e t aL9 showed that freshly mixed propofol and 1% lignocaine reduced the incidence of pain o n injection significantly. Other workers have shown that the addition of lignocaine may reduce the overall incidence of pain on injection into the dorsum of the hand t o less than 9%.’-* These studies may not be directly comparable to ours because of the variations in premedication and the use of pre-induction opioids in some cases. The datasheet supplied by ICI Pharmaceuticals recommends that propofol should be stored a t room temperature; however, direct communication with the company has confirmed that propofol may be stored and administered a t any temperature below 25°C provided that it is not frozen. The exact mechanism for the production of pain with propofol injection remains to be elucidated. Some authors have implicated a kinin c a ~ c a d e ,which ~ would result in a slight delay before pain is experienced. The second pain score in our study was always higher than the first if pain was experienced. The indirect biochemical cascade mechanism may be supported by our findings, in that biochemical
Table 2. Pain assessments after administration of propofol at a temperature of 4 5 ° C (group 1) or at room temperature (group 2). 0 No pain
Mild
2 Moderate
3 Severe
Group 1 n = 34 Group 2
26
3
4
1
n = 37
20
4
5
8
1
Significant difference between column 0 and columns I + 2 + 3 (overall incidence of pain) p < 0.05 (chi-squared test).
reactions might be expected to occur less vigorously a t lower temperatures, and may fail t o reach pain threshold levels in some patients. In conclusion, it appears that the use of propofol a t 45°C may provide a simple and safe method of reducing the incidence of pain o n injection without the addition of other pharmacological agents.
References I . UPPINGTON J, KAYNH, SEARJW. Propofol (‘Diprivan‘)as a supplement to nitrous oxide-oxygen for the maintenance of anaesthesia. Postgraduate Medical Journal 1985; 61 (Suppl. 3): 8&3. 2. BILAINEJ, DESMONTS JM. Effects of premedication with atropine or hydroxyzine on induction and maintenance of anaesthesia with propofol (‘Diprivan’). Postgraduate Medical Journal 1985; 61 (Suppl. 3): 38-9. 3. BRICCS LP, WHITEM. The effects of premedicdtion on anaesthesia with propofol (‘Diprivan’). Postgraduate Medical Journal 1985: 61 (Suppl. 3): 35-7. 4. KNELL PJW, MCKEAN JF. An investigation of the pharmacokinetic profile of propofol (‘Diprivan’) after administration for induction and maintenance of anaesthesia by repeat bolus doses in patients having spinal anaesthetic block. Postgraduate Medical Journal 1985; 61 (Suppl. 3): 60-1. 5. LEESNW, MCCULLOCH M, MAIRWB. Propofol (‘Diprivan’) for induction and maintenance of anaesthesia. Postgraduate Medical Journal 1985; 61 (Suppl. 3): 88-9. 6. STARK RD, BINKSSM, DUTKA VN, OCONNOR K M , AKNSTEIN MJA, GLENJB. A review of the safety and tolerance of propofol (‘Diprivan’). Postgraduate Medical Journal 1985; 61 (SUPPI.3): 152-6. 7. SCOTTRPF, SAUNDERS DA, NORMAN J. Propofol: clinical strategies for preventing the pain of injection. Anaesthesia 1988; 43: 4924. 8. HELBO-HANSEN S, WESTERCARKD V, KROCHBL, SWENDSEN HP. The reduction of pain on injection of propofol; the effects of the addition of lignocaine. Acta Anaesthesiologica Scandinavica 1988; 32: 5 0 2 4 . 9. BKOOKEKJ, HULLCJ, STAFFORD M. Effects of lignocaine on pain caused by propofol injection. Anaesthesia 1985; 4 0 91-2.
