- Email: [email protected]
Potent inhibition of burn pain without use of opiates
Burns 29 (2003) 163–166
Case report
Potent inhibition of burn pain without use of opiates Jean Cassuto a,b,∗ , Peter Tarnow b,c b
a Department of Intensive Care, Sahlgrenska University Hospital, Mölndal, Sweden Institution of Surgical Specialities, Sahlgrenska University Hospital, Gothenburg, Sweden c Department of Plastic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
Accepted 29 August 2002
1. Introduction
2. Case report
Burn pain is often long-lasting, severe and intermittently excruciating due to repeated wound dressings, skin grafts, reconstructive surgery, or other interventional procedures [1]. The severity of pain has established the use of potent opioid analgesics as a standardised mean of inducing analgesia, although pain levels and analgesic requirements are often underestimated in burn patients [2]. A major side-effect encountered in burn patients receiving high doses of opioid analgesics is the pronounced respiratory depression induced by the agents [3], which prompt the use of ventilator support. In the aftermath of the discotheque fire disaster in Gothenburg, 213 patients were triaged within 2 h to four hospitals in the city after having suffered deep partial- or full-thickness skin burns (31 patients) and/or smoke inhalation injuries (158 patients). A significant number of victims required ventilator care either to prevent respiratory failure due to administration of large doses of opioid analgesics and/or to maintain adequate oxygenation secondary to airway injuries, thereby surpassing ventilator capacity. This and similar situations, presenting a severe challenge to limited resources, has urged us to investigate alternative techniques for inducing efficient analgesia in burn patients without the troublesome side-effects of opioid analgesics [4]. A decade ago we presented results on the use of continuous intravenous infusions of lidocaine to produce potent analgesia in major burns without inducing respiratory depression and with few other side effects [5], thereby reducing the need for ventilator support. We present here a case from the discotheque fire disaster in Gothenburg having received this treatment and being particularly illustrative as the patient came to serve as his proper control.
This 18-year-old male (BW 68 kg) was admitted to one of four hospitals in Gothenburg in connection with the discotheque fire disaster in 1998. He tried to escape the fire through the main entrance door but was caught in the cluster of people trapped inside the narrow exit with his back unshielded against the fire raging inside the discotheque [6]. As a result, he suffered burn injuries comprising 18–20% TBSA (deep partial-thickness and full-thickness burns), primarily on his back, left thigh and ear (Fig. 1). On arrival to the emergency on the night of the fire disaster, he exhibited a high level of pain and received 5 mg morphine intravenously. Pain was temporarily subdued. Seven hours after the first administration of morphine, pain reached a new peak and the patient required an additional dose of 9 mg morphine IV (repeated injections of 1 mg per dose within 10 min). Pain relief remained however insufficient. With all available ventilators occupied by other patients who suffered severe smoke inhalation injuries in the fire disaster [6,7], and knowing that the patient ran a substantial risk of developing respiratory depression with continued morphine administration, we reverted to the routine strategy of treating burn pain developed at our hospital and used with excellent results since it was first presented [5]. The patient received a standard dosage scheme used in adult patients. The patient was given an initial intravenous bolus dose of 75 mg lidocaine (Xylocard® 20 mg ml−1 , Astra Zeneca). The bolus dose was followed by a continuous intravenous infusion at 60 ml h−1 of a solution containing 4 mg lidocaine/ml, which was obtained by injecting 2000 mg (= 10 ml) of Xylocard® (200 mg ml−1 ) in 500 ml isotonic saline (corresponding to 3.4 mg kg−1 h−1 in a 70 kg patient). The initial infusion rate of 60 ml h−1 lasted for 4 h, and was subsequently reduced to an infusion rate of 45 ml h−1 (corresponding to 2.6 mg kg−1 h−1 in a 70 kg patient), which lasted during the following 45 h. EKG was continuously monitored by oscilloscope (mandatory) as was blood pressure/heart rate throughout the period of infusion.
∗
Corresponding author. Tel.: +46-31-3431882; fax: +46-31-3431882. E-mail address: [email protected] (J. Cassuto).
0305-4179/03/$30.00 © 2003 Elsevier Science Ltd and ISBI. All rights reserved. PII: S 0 3 0 5 - 4 1 7 9 ( 0 2 ) 0 0 2 3 7 - 1
164
J. Cassuto, P. Tarnow / Burns 29 (2003) 163–166
Fig. 1. This 18-year-old male suffered 18–20% deep partial- and full-thickness burn injuries on his back and thigh after having been caught in the cluster of people trapped inside the entrance of the discotheque.
Fig. 2. Daily requirements of morphine in a patient suffering from 18 to 20% partial- and full-thickness burns and receiving intravenous lidocaine infusion between 8 and 53 h after admission to hospital. Lidocaine infusion was interrupted when patient was moved to another hospital triggering a dramatic increase in morphine requirements.
J. Cassuto, P. Tarnow / Burns 29 (2003) 163–166
Wound dressings were performed on daily basis during this period. Repeated measurements of VAS during the infusion period were all indicated to zero (= no pain) by the patient and no opiate analgesics (= 0 mg) were administered during the period of lidocaine infusion (Fig. 2). The level of carboxyhemoglobin (COHb) upon admission was 14.5% and fell to 2.3% after 12 h. Patient received oxygen on mask as only source of oxygen supply throughout hospital stay and acid–base state remained stable throughout the period of lidocaine infusion as compared to before lidocaine administration (Table 1). Infusion of lidocaine was interrupted when patient had to be moved to another hospital, for plastic reconstructive surgery, which uses traditional pain treatment based on opioid analgesics. A dramatic increase in pain occurred approximately 2 h from termination of the lidocaine infusion and upon arrival to the other hospital. In consequence, the patient had to be given ventilator support before receiving high doses of intravenous fentanyl infusions (50–250 g h−1 ), which lasted during the following 10 days (Fig. 2) and were paralleled by continuous intravenous infusion of propofol (200–600 mg h−1 ). The patient was extubated after 10 days. On the first day after extubation, the patient required 85 mg of ketobemidone (= 85 mg morphine) due to persisting pain. Revisions or wound dressings were performed almost on daily basis at both hospitals during the period accounted for in this report. A standard dose of 1 g paracetamol q.i.d. was given throughout the period of observation in both hospitals. Possible changes in
165
Table 1 Acid–base hemostasis before (0 and 6 h after admission) and during period of lidocaine infusion (12–53 h) Time after admission (h)
pH pCO2 pO2 Base excess SaO2 Bicarbonate
0
6
12
18
30
53
7.40 4.1 19.0 −4.5 98 21
7.46 4.0 32.1 −0.8 100 24
7.32 6.0 30.6 −2.9 99 22
7.42 4.6 17.5 −1.7 99 23
7.38 5.8 19.1 0.3 99 25
7.46 5.2 10.3 3.8 97 28
cardiovascular variables (systolic BP, diastolic BP and heart rate) due to administration of intravenous lidocaine were evaluated by comparison of values before administration of the agent versus values accumulated during the period of administration of lidocaine (Wilcoxon rank sum test). Systolic and diastolic BP remained unchanged during infusion versus period before infusion, while heart rate was slightly but significantly (P = 0.0467) elevated (Fig. 3).
3. Discussion Intravenous lidocaine is a well-documented agent having been given to a large number of patients during the past decades for the treatment of cardiac arrhythmias and is
Fig. 3. Systolic and diastolic blood pressure and heart rate before and after the start of intravenous lidocaine infusion. Systolic and diastolic BP (mmHg) remained unchanged during infusion vs. period before lidocaine administration, while heart rate (beats/min) was slightly but significantly (P = 0.0467) elevated.
166
J. Cassuto, P. Tarnow / Burns 29 (2003) 163–166
still recommended by the American Heart Association as a first-line antiarrhythmic agent in the advanced cardiac life support setting [8]. Aside from the analgesic actions of the agent, the cardiac antiarrhythmogenic effects are equally interesting in burn patients. Cardiac dysfunction during the early phase of a severe burn is a common pathophysiological event and an important cause of refractory chock and multiple organ dysfunction [9]. The use of an agent which safely decreases cardiac work in a burned patient has previously proved beneficial [10]. Burn pain primarily arises from the inflammatory cascade taking place inside the thermally injured tissue and triggered by the destruction of cellular elements. This will set-off the release of a large number of pain-inducing mediators involved in the activation of nociceptive A-delta and C-fibers and in the maintenance of peripheral and central hyperalgesia [11]. Intravenous lidocaine has been shown to suppress pain in a number of painful conditions, including burns [12]. Multiple mechanisms may account for the pain inhibitory actions seen in the present case. Local anaesthetics were recently shown to induce a marked inhibition of PGE from a burn injury in vivo [13], being a central mediator in the promotion of peripheral pain. Moreover, intravenous lidocaine has been shown to depress pain arising from activation of peripheral pain fibers [14] and recently also by inducing potent pain inhibition by influencing central pain mechanisms [15,16]. The present patient did not report any side effects, but a previous investigation [5] showed that a mild euphoria and light-headedness may occur in patients receiving systemic administration of lidocaine. In accordance with previous data [5], the patient responded promptly to the initial bolus dose of lidocaine by indicating a significant degree of pain relief. This pain relief was maintained throughout the period of lidocaine infusion and lasted approximately 2 h after cessation of the infusion, necessitating again the use of high doses of opioid analgesics (Fig. 2). In conclusion, this case where the patient served as his own control, was chosen to illustrate a treatment strategy used to control the severe pain in burn patients which has been in use with us for more than a decade. Intravenous infusion of lidocaine has proven efficient with few dose-dependent side effects and insignificant effects on main cardiovascular variables with the present dosage regimen. It has been shown to significantly reduce both background pain and pain arising from wound dressings as reflected by
VAS scorings and limited need for potent opioid analgesics. In contrast to the previous trial investigating the analgesic effects of intravenous lidocaine where patients served as their own control [5], a future placebo controlled trial is planned comprising two separate groups and investigating in more detail the pain control mechanisms exerted by intravenous lidocaine in burn patients, also including a wider analysis of cardiovascular and stress variables. References [1] Martyn J. Clinical pharmacology and drug therapy in the burned patient. Anesthesiology 1986;65(1):67–75. [2] Latarjet J. The pain from burns. Pathol Biol Paris 2002;50(2):127– 33. [3] Mather LE. Trends in the pharmacology of opioids: implications for the pharmacotherapy of pain. Eur J Pain 2001;5(Suppl A):49– 57. [4] Hedner T, Cassuto J. Opioids and opioid receptors in peripheral tissues. Scand J Gastroenterol Suppl 1987;130:27–46. [5] Jönsson A, Cassuto J, Hanson B. Inhibition of burn pain by intravenous lignocaine infusion. Lancet 1991;338(8760):151–2. [6] Tarnow P, Cassuto J. The discotheque fire disaster in Gothenburg 1998: a tragedy among teenagers. Burns, submitted for publication. [7] Tarnow P, Gewalli F, Cassuto J. Fire disaster in Gotenburg 1998: surgical treatment of burns. Burns, submitted for publication. [8] Chow MS. Advanced cardiac life support controversy: where do antiarrhythmic agents fit in? Pharmacotherapy 1997;17(2 Pt 2):84S– 88S (discussion 89S–91S). [9] Osada M, Tanaka Y, Komai T, et al. QT dispersion in patients with severe burns in intensive care unit. Intensive Care Med 2000;26(10):1581. [10] Baron PW, Barrow RE, Pierre EJ, Herndon DN. Prolonged use of propranolol safely decreases cardiac work in burned children. J Burn Care Rehabil 1997;18(3):223–7. [11] Pedersen JL. Inflammatory pain in experimental burns in man. Dan Med Bull 2000;47(3):168–95. [12] Edwards AD. The role of systemic lidocaine in neuropathic pain management. J Intraven Nurs 1999;22(5):273–9. [13] Yregård L, Cassuto J, Tarnow P, Nilsson U. Inhibition by local anesthetics (EMLA) of inflammatory activity postburn. Burns, submitted for publication. [14] Thorén P, Öberg B. Studies on the endoanesthetic effects of lidocaine and benzonatate on non-medullated nerve endings in the left ventricle. Acta Physiol Scand 1981;111(1):51–8. [15] Attal N, Gaude V, Brasseur L, et al. Intravenous lidocaine in central pain: a double-blind, placebo-controlled, psychophysical study. Neurology 2000;54(3):564–74. [16] Abelson KS, Hoglund AU. Intravenously administered lidocaine in therapeutic doses increases the intraspinal release of acetylcholine in rats. Neurosci Lett 2002;317(2):93–6.
Case report
Potent inhibition of burn pain without use of opiates Jean Cassuto a,b,∗ , Peter Tarnow b,c b
a Department of Intensive Care, Sahlgrenska University Hospital, Mölndal, Sweden Institution of Surgical Specialities, Sahlgrenska University Hospital, Gothenburg, Sweden c Department of Plastic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
Accepted 29 August 2002
1. Introduction
2. Case report
Burn pain is often long-lasting, severe and intermittently excruciating due to repeated wound dressings, skin grafts, reconstructive surgery, or other interventional procedures [1]. The severity of pain has established the use of potent opioid analgesics as a standardised mean of inducing analgesia, although pain levels and analgesic requirements are often underestimated in burn patients [2]. A major side-effect encountered in burn patients receiving high doses of opioid analgesics is the pronounced respiratory depression induced by the agents [3], which prompt the use of ventilator support. In the aftermath of the discotheque fire disaster in Gothenburg, 213 patients were triaged within 2 h to four hospitals in the city after having suffered deep partial- or full-thickness skin burns (31 patients) and/or smoke inhalation injuries (158 patients). A significant number of victims required ventilator care either to prevent respiratory failure due to administration of large doses of opioid analgesics and/or to maintain adequate oxygenation secondary to airway injuries, thereby surpassing ventilator capacity. This and similar situations, presenting a severe challenge to limited resources, has urged us to investigate alternative techniques for inducing efficient analgesia in burn patients without the troublesome side-effects of opioid analgesics [4]. A decade ago we presented results on the use of continuous intravenous infusions of lidocaine to produce potent analgesia in major burns without inducing respiratory depression and with few other side effects [5], thereby reducing the need for ventilator support. We present here a case from the discotheque fire disaster in Gothenburg having received this treatment and being particularly illustrative as the patient came to serve as his proper control.
This 18-year-old male (BW 68 kg) was admitted to one of four hospitals in Gothenburg in connection with the discotheque fire disaster in 1998. He tried to escape the fire through the main entrance door but was caught in the cluster of people trapped inside the narrow exit with his back unshielded against the fire raging inside the discotheque [6]. As a result, he suffered burn injuries comprising 18–20% TBSA (deep partial-thickness and full-thickness burns), primarily on his back, left thigh and ear (Fig. 1). On arrival to the emergency on the night of the fire disaster, he exhibited a high level of pain and received 5 mg morphine intravenously. Pain was temporarily subdued. Seven hours after the first administration of morphine, pain reached a new peak and the patient required an additional dose of 9 mg morphine IV (repeated injections of 1 mg per dose within 10 min). Pain relief remained however insufficient. With all available ventilators occupied by other patients who suffered severe smoke inhalation injuries in the fire disaster [6,7], and knowing that the patient ran a substantial risk of developing respiratory depression with continued morphine administration, we reverted to the routine strategy of treating burn pain developed at our hospital and used with excellent results since it was first presented [5]. The patient received a standard dosage scheme used in adult patients. The patient was given an initial intravenous bolus dose of 75 mg lidocaine (Xylocard® 20 mg ml−1 , Astra Zeneca). The bolus dose was followed by a continuous intravenous infusion at 60 ml h−1 of a solution containing 4 mg lidocaine/ml, which was obtained by injecting 2000 mg (= 10 ml) of Xylocard® (200 mg ml−1 ) in 500 ml isotonic saline (corresponding to 3.4 mg kg−1 h−1 in a 70 kg patient). The initial infusion rate of 60 ml h−1 lasted for 4 h, and was subsequently reduced to an infusion rate of 45 ml h−1 (corresponding to 2.6 mg kg−1 h−1 in a 70 kg patient), which lasted during the following 45 h. EKG was continuously monitored by oscilloscope (mandatory) as was blood pressure/heart rate throughout the period of infusion.
∗
Corresponding author. Tel.: +46-31-3431882; fax: +46-31-3431882. E-mail address: [email protected] (J. Cassuto).
0305-4179/03/$30.00 © 2003 Elsevier Science Ltd and ISBI. All rights reserved. PII: S 0 3 0 5 - 4 1 7 9 ( 0 2 ) 0 0 2 3 7 - 1
164
J. Cassuto, P. Tarnow / Burns 29 (2003) 163–166
Fig. 1. This 18-year-old male suffered 18–20% deep partial- and full-thickness burn injuries on his back and thigh after having been caught in the cluster of people trapped inside the entrance of the discotheque.
Fig. 2. Daily requirements of morphine in a patient suffering from 18 to 20% partial- and full-thickness burns and receiving intravenous lidocaine infusion between 8 and 53 h after admission to hospital. Lidocaine infusion was interrupted when patient was moved to another hospital triggering a dramatic increase in morphine requirements.
J. Cassuto, P. Tarnow / Burns 29 (2003) 163–166
Wound dressings were performed on daily basis during this period. Repeated measurements of VAS during the infusion period were all indicated to zero (= no pain) by the patient and no opiate analgesics (= 0 mg) were administered during the period of lidocaine infusion (Fig. 2). The level of carboxyhemoglobin (COHb) upon admission was 14.5% and fell to 2.3% after 12 h. Patient received oxygen on mask as only source of oxygen supply throughout hospital stay and acid–base state remained stable throughout the period of lidocaine infusion as compared to before lidocaine administration (Table 1). Infusion of lidocaine was interrupted when patient had to be moved to another hospital, for plastic reconstructive surgery, which uses traditional pain treatment based on opioid analgesics. A dramatic increase in pain occurred approximately 2 h from termination of the lidocaine infusion and upon arrival to the other hospital. In consequence, the patient had to be given ventilator support before receiving high doses of intravenous fentanyl infusions (50–250 g h−1 ), which lasted during the following 10 days (Fig. 2) and were paralleled by continuous intravenous infusion of propofol (200–600 mg h−1 ). The patient was extubated after 10 days. On the first day after extubation, the patient required 85 mg of ketobemidone (= 85 mg morphine) due to persisting pain. Revisions or wound dressings were performed almost on daily basis at both hospitals during the period accounted for in this report. A standard dose of 1 g paracetamol q.i.d. was given throughout the period of observation in both hospitals. Possible changes in
165
Table 1 Acid–base hemostasis before (0 and 6 h after admission) and during period of lidocaine infusion (12–53 h) Time after admission (h)
pH pCO2 pO2 Base excess SaO2 Bicarbonate
0
6
12
18
30
53
7.40 4.1 19.0 −4.5 98 21
7.46 4.0 32.1 −0.8 100 24
7.32 6.0 30.6 −2.9 99 22
7.42 4.6 17.5 −1.7 99 23
7.38 5.8 19.1 0.3 99 25
7.46 5.2 10.3 3.8 97 28
cardiovascular variables (systolic BP, diastolic BP and heart rate) due to administration of intravenous lidocaine were evaluated by comparison of values before administration of the agent versus values accumulated during the period of administration of lidocaine (Wilcoxon rank sum test). Systolic and diastolic BP remained unchanged during infusion versus period before infusion, while heart rate was slightly but significantly (P = 0.0467) elevated (Fig. 3).
3. Discussion Intravenous lidocaine is a well-documented agent having been given to a large number of patients during the past decades for the treatment of cardiac arrhythmias and is
Fig. 3. Systolic and diastolic blood pressure and heart rate before and after the start of intravenous lidocaine infusion. Systolic and diastolic BP (mmHg) remained unchanged during infusion vs. period before lidocaine administration, while heart rate (beats/min) was slightly but significantly (P = 0.0467) elevated.
166
J. Cassuto, P. Tarnow / Burns 29 (2003) 163–166
still recommended by the American Heart Association as a first-line antiarrhythmic agent in the advanced cardiac life support setting [8]. Aside from the analgesic actions of the agent, the cardiac antiarrhythmogenic effects are equally interesting in burn patients. Cardiac dysfunction during the early phase of a severe burn is a common pathophysiological event and an important cause of refractory chock and multiple organ dysfunction [9]. The use of an agent which safely decreases cardiac work in a burned patient has previously proved beneficial [10]. Burn pain primarily arises from the inflammatory cascade taking place inside the thermally injured tissue and triggered by the destruction of cellular elements. This will set-off the release of a large number of pain-inducing mediators involved in the activation of nociceptive A-delta and C-fibers and in the maintenance of peripheral and central hyperalgesia [11]. Intravenous lidocaine has been shown to suppress pain in a number of painful conditions, including burns [12]. Multiple mechanisms may account for the pain inhibitory actions seen in the present case. Local anaesthetics were recently shown to induce a marked inhibition of PGE from a burn injury in vivo [13], being a central mediator in the promotion of peripheral pain. Moreover, intravenous lidocaine has been shown to depress pain arising from activation of peripheral pain fibers [14] and recently also by inducing potent pain inhibition by influencing central pain mechanisms [15,16]. The present patient did not report any side effects, but a previous investigation [5] showed that a mild euphoria and light-headedness may occur in patients receiving systemic administration of lidocaine. In accordance with previous data [5], the patient responded promptly to the initial bolus dose of lidocaine by indicating a significant degree of pain relief. This pain relief was maintained throughout the period of lidocaine infusion and lasted approximately 2 h after cessation of the infusion, necessitating again the use of high doses of opioid analgesics (Fig. 2). In conclusion, this case where the patient served as his own control, was chosen to illustrate a treatment strategy used to control the severe pain in burn patients which has been in use with us for more than a decade. Intravenous infusion of lidocaine has proven efficient with few dose-dependent side effects and insignificant effects on main cardiovascular variables with the present dosage regimen. It has been shown to significantly reduce both background pain and pain arising from wound dressings as reflected by
VAS scorings and limited need for potent opioid analgesics. In contrast to the previous trial investigating the analgesic effects of intravenous lidocaine where patients served as their own control [5], a future placebo controlled trial is planned comprising two separate groups and investigating in more detail the pain control mechanisms exerted by intravenous lidocaine in burn patients, also including a wider analysis of cardiovascular and stress variables. References [1] Martyn J. Clinical pharmacology and drug therapy in the burned patient. Anesthesiology 1986;65(1):67–75. [2] Latarjet J. The pain from burns. Pathol Biol Paris 2002;50(2):127– 33. [3] Mather LE. Trends in the pharmacology of opioids: implications for the pharmacotherapy of pain. Eur J Pain 2001;5(Suppl A):49– 57. [4] Hedner T, Cassuto J. Opioids and opioid receptors in peripheral tissues. Scand J Gastroenterol Suppl 1987;130:27–46. [5] Jönsson A, Cassuto J, Hanson B. Inhibition of burn pain by intravenous lignocaine infusion. Lancet 1991;338(8760):151–2. [6] Tarnow P, Cassuto J. The discotheque fire disaster in Gothenburg 1998: a tragedy among teenagers. Burns, submitted for publication. [7] Tarnow P, Gewalli F, Cassuto J. Fire disaster in Gotenburg 1998: surgical treatment of burns. Burns, submitted for publication. [8] Chow MS. Advanced cardiac life support controversy: where do antiarrhythmic agents fit in? Pharmacotherapy 1997;17(2 Pt 2):84S– 88S (discussion 89S–91S). [9] Osada M, Tanaka Y, Komai T, et al. QT dispersion in patients with severe burns in intensive care unit. Intensive Care Med 2000;26(10):1581. [10] Baron PW, Barrow RE, Pierre EJ, Herndon DN. Prolonged use of propranolol safely decreases cardiac work in burned children. J Burn Care Rehabil 1997;18(3):223–7. [11] Pedersen JL. Inflammatory pain in experimental burns in man. Dan Med Bull 2000;47(3):168–95. [12] Edwards AD. The role of systemic lidocaine in neuropathic pain management. J Intraven Nurs 1999;22(5):273–9. [13] Yregård L, Cassuto J, Tarnow P, Nilsson U. Inhibition by local anesthetics (EMLA) of inflammatory activity postburn. Burns, submitted for publication. [14] Thorén P, Öberg B. Studies on the endoanesthetic effects of lidocaine and benzonatate on non-medullated nerve endings in the left ventricle. Acta Physiol Scand 1981;111(1):51–8. [15] Attal N, Gaude V, Brasseur L, et al. Intravenous lidocaine in central pain: a double-blind, placebo-controlled, psychophysical study. Neurology 2000;54(3):564–74. [16] Abelson KS, Hoglund AU. Intravenously administered lidocaine in therapeutic doses increases the intraspinal release of acetylcholine in rats. Neurosci Lett 2002;317(2):93–6.