- Email: [email protected]
Inhibition of burn pain by intravenous lignocaine infusion
151
remained low for the next two days. With improvement of clinical status, serum iron returned to normal. Our results show that virtually all episodes of NMS are accompanied by a pronounced reduction in serum iron concentration. Thus, serum iron may be a useful biochemical marker for NMS, and a helpful adjunct in the diagnosis of the disorder. What are the reasons for the striking decrease in serum iron? Although infections may produce such a decrease, only 3 of our 26 episodes were accompanied by infection. In two of these three patients, infection predated the NMS; in both cases serum iron, which had been measured before the onset of NMS, fell by at least 60% from pre-NMS values. None of the patients was anaemic at the time of NMS. Is NMS an acute phase reaction (APR)? This complex physiological response to, for example, inflammation, infection, and muscle injury sets off a wide range of events, including fever, leucocytosis, muscle breakdown, and hypoferraemia, all of which are characteristic of NMS. Interleukins 1 and 6 (IL-1, IL-6) mediate many of these changes. Hypoferraemia is believed to be due to release of lactoferrin from granulocytes; lactoferrin then carries iron to the liver where it is deposited as ferritin.3 The mechanism by which the APR might be initiated in NMS is unclear. In six of our patients there was a correlation between hypoferraemia and serum CK. The relation between muscle injury and the APR is complex. On the one hand acute muscle injury-eg, that resulting from strenuous exercise4 or myocardial infarction5-can initiate the APR. On the other hand acute phase proteins stimulate muscle proteolysis by a mechanism involving prostaglandin E2.6 Neuroleptics produce muscle dystonia and rigidity, either of which could compromise muscle cell integrity and initiate the APR. However, since most neuroleptic-treated patients with these common side-effects do not go on to have NMS, other factors are probably involved. It is possible that the large decrease in serum iron during NMS plays a part in the pathophysiology of the disorder. Iron is present in relatively large quantities in the brain and its distribution roughly parallels that of dopamine, with the highest concentrations in the basal ganglia.7 There is evidence that iron may be integral to normal function of the dopamine D2 receptor.2 Rats made iron-deficient have a reduced response to the dopamine-mediated behavioural and physiological effects of amorphine, and have fewer D2 receptors, without any apparent change in Dreceptors.2 Clinical studies have further underlined the association between serum iron and D2 receptor function. In 1960, Ekbom reported that "restless legs" syndrome is associated with iron deficiency anaemia. It has since been recognised that this syndrome is virtually identical to neurolepticinduced akathisia, which is thought to be related to D2 receptor blockaded Brown and colleagues9 have reported that patients with neuroleptic-induced akathisia have lower serum iron than matched neuroleptic-treated controls. Our hypothesis of the relation of serum iron to NMS is as follows. An unknown initiating event induces a sudden decrease of serum iron, perhaps by initiating the APR. The reduction of serum iron may then lead to decreased numbers of dopamine D2 receptors in the brain. In the presence of neuroleptic medication, this loss of receptors may trigger an acute reduction of dopaminergic function, thereby
potentially contributing to the rigidity, staring, and mutism that are characteristic of NMS. The notion that NMS may represent a form of the APR may have therapeutic implications. Many of the features of
the APR are mediated by prostaglandin E2,6 which can be inhibited by various medications, including salicylates and paracetamol (acetaminophen). If NMS is an example of the APR, these drugs might be the most appropriate therapeutic agents. We have previously found that patients with NMS respond well to such agents and that dantrolene and bromocriptine seem to confer no additional benefit. 10 M. F. M. is
a career
scientist of the Ontario
Ministry of Health.
REFERENCES PI, Stewart TD. A prospective analysis of 24 episodes of neuroleptic malignant syndrome. Am J Psychiatry 1989; 146: 717-25. 2. Ben-Shachar D, Finberg JPM, Youdim MBH. Effect of iron chelators on dopamine D2 receptors. J Neurochem 1985; 45: 999-1005. 3. Goldblum SE, Cohen DA, Jay M, McClain CJ. Interleukin 1-induced depression of iron and zinc: role of granulocyte and lactoferrin. Am J Physiol 1987; 252: E27-E32. 4. Taylor C, Rogers G, Goodman C, et al. Hematologic, iron-related and acute-phase protein responses to sustained strenuous exercise. J Appl Physiol 1987; 62: 464-69. 5. Griffiths JD, Campbell IJ, Woodruff IW, et al. Acute changes in iron metabolism following myocardial infarction. Am J Clin Pathol 1985; 1. Rosebush
84: 649-54. 6. Baracos V, Rodemann HP, Dinarello CA, Goldberg AL. Stimulation of muscle protein degradation and prostaglandin E2 release by leukocytic pyrogen (interleukin 1). N Engl J Med 1983; 308: 553-58. 7. Riederer P, Sofic E, Rausch WD, et al. Transition metals, ferritin, glutathione and ascorbic acid in parkinsonian brains. J Neurochem
1989; 52: 515-20. 8. Editorial. Akathisia and antipsychotic drugs. Lancet 1986; ii: 1131-32. 9. Brown KW, Glen SE, White T. Low serum iron status and akathisia. Lancet 1987; ii: 1234-35. 10. Rosebush PI, Stewart T, Mazurek MF. Treatment of neuroleptic malignant syndrome: are dantrolene and bromocriptine useful adjuncts to
supportive care. Br J Psychiatry (in press).
ADDRESSES: Departments of Psychiatry (P I. Rosebush, FRCPC), Medicine (M. F. Mazurek, FRCPC), and Biomedical Sciences (M. F. Mazurek), McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada. Correspondence to Dr P. I. Rosebush.
Inhibition of burn pain by intravenous lignocaine infusion
Patients with
burns often suffer severe pain, especially during dressing of wounds, but there are no established alternatives to potent opiate analgesics, with their various side-effects. Intravenous lignocaine infusion strikingly reduced self-assessed pain scores in 7 patients during the first 3 days after second-degree burns, without need for
supplementary opiate analgesia.
Pain after bum injuries is often severe and requires use of potent opiate analgesics, which have side-effects such as sedation, nausea, and vomiting. Fear of addiction to narcotics or development of tolerance may also contribute to
152
scores from 7 patients with 10-30% second-degree burns during, between, and after intravenous lignocaine infusions.
Pain
Median values shown; bars descnbe range.
undermedication and ineffective analgesia. Continuous intravenous lignocaine infusion reduces postoperative pain ;2 are similar analgesic effects observed among patients with bums? 7 patients (4 female, 3 male), with 10-30% second-degree burns caused by hot water or steam, filled in a visual analogue pain scale (VAS) that ranged from 0 (no pain) to 100 (unbearable pain) immediately after admission to hospital, and then received 1-5 mg/kg pethidine intramuscularly. 1 h later the patient again assessed pain by VAS: if the score was over 50, the patient was given 1 mg/kg intravenous lignocaine (Astra, Hassle, Sweden) as a bolus dose, followed by continuous intravenous infusion at 40 µg/kg per min (made up as 2 g lignocaine in 500 ml isotonic saline). Pain was assessed by VAS every 2 h. After 18 h, the infusion was interrupted for up to 6 h to assess the underlying severity of pain: if VAS scores remained below 50 the infusion was stopped and the patient offered opiate analgesics. When the pain score exceeded 50, a new bolus dose and a continuous infusion of lignocaine were given as before. Lignocaine infusion was continued for up to 3 days, with the patient as his or her own control. VAS scores were also measured 4 hourly for at least 2 days after discontinuation of the lignocaine infusion. Pain score was also measured whenever wounds were dressed; additional bolus doses of 50 mg lignocaine were administered intravenously if required during wound nursing care. 0-5 mg/kg intravenous pethidine was given if other analgesia was ineffective during any part of the study. All patients were continuously monitored by electrocardiography and blood pressure was measured hourly. The Wilcoxon signed rank test was used for statistical analysis.
All patients were admitted to hospital within 6 h of injury. Median (range) VAS pain score upon admission and before opiate administration was 96 (83-98), and fell to 81 (63-86) 1 h after intramuscular pethidine. 2 h after the start of the lignocaine infusion, pain score fell significantly to 17 (5-24) (p<0.05 &ugr;s 1 h after pethidine administration). When lignocaine infusion was interrupted pain score did not change significantly by 2 h (21 [8-34]), but increased significantly after 4 h (47 [32-54]) and 6 h (64 [58-70]) (p<0’05 &ngr;s last VAS score before infusion stopped; see figure). All patients had a pain score above 50 after 6 h without lignocaine infusion for the first 3 days after injury, and lignocaine was restarted as before. No patient required extra pethidine during these first 3 days. After the infusion was stopped at the end of the third day after injury, pain scores increased to a steady state median value of 32-48 (see figure); during the fourth day of the study patients were given 315 (275-350) mg pethidine intramuscularly, and 225 (150-250) mg during the fifth day after injury. All patients had their wounds dressed 2-4 times daily. 5 required no additional analgesia during the period of lignocaine infusion. In 2 patients who had severe pain (VAS above 50), additional bolus doses of 50 mg lignocaine intravenously immediately before the procedure allowed wounds to be dressed with very little pain (VAS below 20).
No patient requested additional opiate analgesia during wound dressing. 4 patients reported euphoria during the lignocaine infusion and 1 reported light-headedness after the initial bolus dose, probably because of over-rapid injection. No cardiovascular or other side-effects to lignocaine were reported or observed. Several mechanisms may account for our findings. Systemic lignocaine depresses conduction in pain afferent nerves,; inhibits dorsal horn neural transmission,4 and may modify cerebral perception of pain. Bum injury is likely to trigger the release of inflammatory agents such as histamine, serotonin, and prostaglandinswhich could cause pain; local anaesthetics such as lignocaine have potent antiinflammatory effects,79 which may partly account for their analgesic effects in an inflamed bum wound. Topical as well as systemic local anaesthetics significantly reduce experimental oedema formation in bums at concentrations below those likely to cause systemic side-effects.1o Lignocaine infusion may be a valuable additional analgesic option in patients with burns. Pain scores were strikingly reduced and opiate analgesics not routinely required in these 7 patients shortly after injury, when pain is usually most intense;l even during dressing of wounds only 2 patients required extra analgesic. The euphoric effect of lignocaine in 4 of the 7 patients may have helped to reduce their anxiety, a common feature in burns patients;’ other important adverse side-effects were not noted. This work
was
supported by grants from Bohuslandstinget.
REFERENCES 1. Choinière M. The pain of burns. In: Wall PD, Melzack R, eds. The textbook of pain. London: Churchill Livingstone, 1989: 402-08. 2. Cassuto J, Wallin G, Hogstrom S, Faxén A, Rimback G. Inhibition of postoperative pain by continuous low-dose intravenous infusion of lidocaine. Anesth Analg 1985; 64: 971-74. 3. 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: 51-58. 4. Woolf CJ, Wiesenfeld-Hallin Z. The systemic administration of local anaesthetics produces a selective depression of C-afferent fibre evoked activity in the spinal cord. Pain 1985; 23: 361-74. 5. Garfield JM, Gugino L. Central effects of local anesthetic agents. In: Strichartz GR, ed. Local anesthetics. Berlin: Springer-Verlag, 1987: 253-84. 6. Arturson G. Possible involvement of arachidonic acid metabolites in thermal trauma. In: Dolecek R, Brizio-Molteni L, Molteni A, Traber D, eds. Endocrinology of thermal trauma. London: Lea and Febiger, 1990: 238-50. 7. Horrobin DF, Manku MS. Roles of prostaglan dins suggested by the medical anaesthetic, antiprostaglandin agonist/antagonist actions
8.
and anti-malarial, arrhythmic, tricyclic anti-depressant methylxanthine compounds, effects on membranes and on nucleic acid function. Med Hypotheses 1977; 3: 71-86. Peck SL, Johnston RB, Horrowitz LD. Reduced neutrophil superoxide anion release after prolonged infusion of lidocaine. J Pharmacol Exp
Ther 1985; 235: 418-22. 8. Rimback G, Cassuto J, Wallin G, Westlander G. Inhibition of peritonitis by amide local anesthetics. Anesthesiology 1988; 69: 881-86. 10. Cassuto J, Nellgård P, Stage L, Jonsson A. Amide local anesthetics reduce albumin extravasation in burn injuries. Anesthesiology 1990; 72: 302-07.
ADDRESSES Department of Anaesthesia and Intensive Care Unit (J Cassuto, MD, B Hanson, MD), and Department of Surgery (A Jonsson, MD), Central Hospital, Mölndal, Sweden. Correspondence to Dr J Cassuto, Department of Anaesthesia and Intensive Care Unit, Central Hospital, S-431 80 Molndal, Sweden
remained low for the next two days. With improvement of clinical status, serum iron returned to normal. Our results show that virtually all episodes of NMS are accompanied by a pronounced reduction in serum iron concentration. Thus, serum iron may be a useful biochemical marker for NMS, and a helpful adjunct in the diagnosis of the disorder. What are the reasons for the striking decrease in serum iron? Although infections may produce such a decrease, only 3 of our 26 episodes were accompanied by infection. In two of these three patients, infection predated the NMS; in both cases serum iron, which had been measured before the onset of NMS, fell by at least 60% from pre-NMS values. None of the patients was anaemic at the time of NMS. Is NMS an acute phase reaction (APR)? This complex physiological response to, for example, inflammation, infection, and muscle injury sets off a wide range of events, including fever, leucocytosis, muscle breakdown, and hypoferraemia, all of which are characteristic of NMS. Interleukins 1 and 6 (IL-1, IL-6) mediate many of these changes. Hypoferraemia is believed to be due to release of lactoferrin from granulocytes; lactoferrin then carries iron to the liver where it is deposited as ferritin.3 The mechanism by which the APR might be initiated in NMS is unclear. In six of our patients there was a correlation between hypoferraemia and serum CK. The relation between muscle injury and the APR is complex. On the one hand acute muscle injury-eg, that resulting from strenuous exercise4 or myocardial infarction5-can initiate the APR. On the other hand acute phase proteins stimulate muscle proteolysis by a mechanism involving prostaglandin E2.6 Neuroleptics produce muscle dystonia and rigidity, either of which could compromise muscle cell integrity and initiate the APR. However, since most neuroleptic-treated patients with these common side-effects do not go on to have NMS, other factors are probably involved. It is possible that the large decrease in serum iron during NMS plays a part in the pathophysiology of the disorder. Iron is present in relatively large quantities in the brain and its distribution roughly parallels that of dopamine, with the highest concentrations in the basal ganglia.7 There is evidence that iron may be integral to normal function of the dopamine D2 receptor.2 Rats made iron-deficient have a reduced response to the dopamine-mediated behavioural and physiological effects of amorphine, and have fewer D2 receptors, without any apparent change in Dreceptors.2 Clinical studies have further underlined the association between serum iron and D2 receptor function. In 1960, Ekbom reported that "restless legs" syndrome is associated with iron deficiency anaemia. It has since been recognised that this syndrome is virtually identical to neurolepticinduced akathisia, which is thought to be related to D2 receptor blockaded Brown and colleagues9 have reported that patients with neuroleptic-induced akathisia have lower serum iron than matched neuroleptic-treated controls. Our hypothesis of the relation of serum iron to NMS is as follows. An unknown initiating event induces a sudden decrease of serum iron, perhaps by initiating the APR. The reduction of serum iron may then lead to decreased numbers of dopamine D2 receptors in the brain. In the presence of neuroleptic medication, this loss of receptors may trigger an acute reduction of dopaminergic function, thereby
potentially contributing to the rigidity, staring, and mutism that are characteristic of NMS. The notion that NMS may represent a form of the APR may have therapeutic implications. Many of the features of
the APR are mediated by prostaglandin E2,6 which can be inhibited by various medications, including salicylates and paracetamol (acetaminophen). If NMS is an example of the APR, these drugs might be the most appropriate therapeutic agents. We have previously found that patients with NMS respond well to such agents and that dantrolene and bromocriptine seem to confer no additional benefit. 10 M. F. M. is
a career
scientist of the Ontario
Ministry of Health.
REFERENCES PI, Stewart TD. A prospective analysis of 24 episodes of neuroleptic malignant syndrome. Am J Psychiatry 1989; 146: 717-25. 2. Ben-Shachar D, Finberg JPM, Youdim MBH. Effect of iron chelators on dopamine D2 receptors. J Neurochem 1985; 45: 999-1005. 3. Goldblum SE, Cohen DA, Jay M, McClain CJ. Interleukin 1-induced depression of iron and zinc: role of granulocyte and lactoferrin. Am J Physiol 1987; 252: E27-E32. 4. Taylor C, Rogers G, Goodman C, et al. Hematologic, iron-related and acute-phase protein responses to sustained strenuous exercise. J Appl Physiol 1987; 62: 464-69. 5. Griffiths JD, Campbell IJ, Woodruff IW, et al. Acute changes in iron metabolism following myocardial infarction. Am J Clin Pathol 1985; 1. Rosebush
84: 649-54. 6. Baracos V, Rodemann HP, Dinarello CA, Goldberg AL. Stimulation of muscle protein degradation and prostaglandin E2 release by leukocytic pyrogen (interleukin 1). N Engl J Med 1983; 308: 553-58. 7. Riederer P, Sofic E, Rausch WD, et al. Transition metals, ferritin, glutathione and ascorbic acid in parkinsonian brains. J Neurochem
1989; 52: 515-20. 8. Editorial. Akathisia and antipsychotic drugs. Lancet 1986; ii: 1131-32. 9. Brown KW, Glen SE, White T. Low serum iron status and akathisia. Lancet 1987; ii: 1234-35. 10. Rosebush PI, Stewart T, Mazurek MF. Treatment of neuroleptic malignant syndrome: are dantrolene and bromocriptine useful adjuncts to
supportive care. Br J Psychiatry (in press).
ADDRESSES: Departments of Psychiatry (P I. Rosebush, FRCPC), Medicine (M. F. Mazurek, FRCPC), and Biomedical Sciences (M. F. Mazurek), McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada. Correspondence to Dr P. I. Rosebush.
Inhibition of burn pain by intravenous lignocaine infusion
Patients with
burns often suffer severe pain, especially during dressing of wounds, but there are no established alternatives to potent opiate analgesics, with their various side-effects. Intravenous lignocaine infusion strikingly reduced self-assessed pain scores in 7 patients during the first 3 days after second-degree burns, without need for
supplementary opiate analgesia.
Pain after bum injuries is often severe and requires use of potent opiate analgesics, which have side-effects such as sedation, nausea, and vomiting. Fear of addiction to narcotics or development of tolerance may also contribute to
152
scores from 7 patients with 10-30% second-degree burns during, between, and after intravenous lignocaine infusions.
Pain
Median values shown; bars descnbe range.
undermedication and ineffective analgesia. Continuous intravenous lignocaine infusion reduces postoperative pain ;2 are similar analgesic effects observed among patients with bums? 7 patients (4 female, 3 male), with 10-30% second-degree burns caused by hot water or steam, filled in a visual analogue pain scale (VAS) that ranged from 0 (no pain) to 100 (unbearable pain) immediately after admission to hospital, and then received 1-5 mg/kg pethidine intramuscularly. 1 h later the patient again assessed pain by VAS: if the score was over 50, the patient was given 1 mg/kg intravenous lignocaine (Astra, Hassle, Sweden) as a bolus dose, followed by continuous intravenous infusion at 40 µg/kg per min (made up as 2 g lignocaine in 500 ml isotonic saline). Pain was assessed by VAS every 2 h. After 18 h, the infusion was interrupted for up to 6 h to assess the underlying severity of pain: if VAS scores remained below 50 the infusion was stopped and the patient offered opiate analgesics. When the pain score exceeded 50, a new bolus dose and a continuous infusion of lignocaine were given as before. Lignocaine infusion was continued for up to 3 days, with the patient as his or her own control. VAS scores were also measured 4 hourly for at least 2 days after discontinuation of the lignocaine infusion. Pain score was also measured whenever wounds were dressed; additional bolus doses of 50 mg lignocaine were administered intravenously if required during wound nursing care. 0-5 mg/kg intravenous pethidine was given if other analgesia was ineffective during any part of the study. All patients were continuously monitored by electrocardiography and blood pressure was measured hourly. The Wilcoxon signed rank test was used for statistical analysis.
All patients were admitted to hospital within 6 h of injury. Median (range) VAS pain score upon admission and before opiate administration was 96 (83-98), and fell to 81 (63-86) 1 h after intramuscular pethidine. 2 h after the start of the lignocaine infusion, pain score fell significantly to 17 (5-24) (p<0.05 &ugr;s 1 h after pethidine administration). When lignocaine infusion was interrupted pain score did not change significantly by 2 h (21 [8-34]), but increased significantly after 4 h (47 [32-54]) and 6 h (64 [58-70]) (p<0’05 &ngr;s last VAS score before infusion stopped; see figure). All patients had a pain score above 50 after 6 h without lignocaine infusion for the first 3 days after injury, and lignocaine was restarted as before. No patient required extra pethidine during these first 3 days. After the infusion was stopped at the end of the third day after injury, pain scores increased to a steady state median value of 32-48 (see figure); during the fourth day of the study patients were given 315 (275-350) mg pethidine intramuscularly, and 225 (150-250) mg during the fifth day after injury. All patients had their wounds dressed 2-4 times daily. 5 required no additional analgesia during the period of lignocaine infusion. In 2 patients who had severe pain (VAS above 50), additional bolus doses of 50 mg lignocaine intravenously immediately before the procedure allowed wounds to be dressed with very little pain (VAS below 20).
No patient requested additional opiate analgesia during wound dressing. 4 patients reported euphoria during the lignocaine infusion and 1 reported light-headedness after the initial bolus dose, probably because of over-rapid injection. No cardiovascular or other side-effects to lignocaine were reported or observed. Several mechanisms may account for our findings. Systemic lignocaine depresses conduction in pain afferent nerves,; inhibits dorsal horn neural transmission,4 and may modify cerebral perception of pain. Bum injury is likely to trigger the release of inflammatory agents such as histamine, serotonin, and prostaglandinswhich could cause pain; local anaesthetics such as lignocaine have potent antiinflammatory effects,79 which may partly account for their analgesic effects in an inflamed bum wound. Topical as well as systemic local anaesthetics significantly reduce experimental oedema formation in bums at concentrations below those likely to cause systemic side-effects.1o Lignocaine infusion may be a valuable additional analgesic option in patients with burns. Pain scores were strikingly reduced and opiate analgesics not routinely required in these 7 patients shortly after injury, when pain is usually most intense;l even during dressing of wounds only 2 patients required extra analgesic. The euphoric effect of lignocaine in 4 of the 7 patients may have helped to reduce their anxiety, a common feature in burns patients;’ other important adverse side-effects were not noted. This work
was
supported by grants from Bohuslandstinget.
REFERENCES 1. Choinière M. The pain of burns. In: Wall PD, Melzack R, eds. The textbook of pain. London: Churchill Livingstone, 1989: 402-08. 2. Cassuto J, Wallin G, Hogstrom S, Faxén A, Rimback G. Inhibition of postoperative pain by continuous low-dose intravenous infusion of lidocaine. Anesth Analg 1985; 64: 971-74. 3. 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: 51-58. 4. Woolf CJ, Wiesenfeld-Hallin Z. The systemic administration of local anaesthetics produces a selective depression of C-afferent fibre evoked activity in the spinal cord. Pain 1985; 23: 361-74. 5. Garfield JM, Gugino L. Central effects of local anesthetic agents. In: Strichartz GR, ed. Local anesthetics. Berlin: Springer-Verlag, 1987: 253-84. 6. Arturson G. Possible involvement of arachidonic acid metabolites in thermal trauma. In: Dolecek R, Brizio-Molteni L, Molteni A, Traber D, eds. Endocrinology of thermal trauma. London: Lea and Febiger, 1990: 238-50. 7. Horrobin DF, Manku MS. Roles of prostaglan dins suggested by the medical anaesthetic, antiprostaglandin agonist/antagonist actions
8.
and anti-malarial, arrhythmic, tricyclic anti-depressant methylxanthine compounds, effects on membranes and on nucleic acid function. Med Hypotheses 1977; 3: 71-86. Peck SL, Johnston RB, Horrowitz LD. Reduced neutrophil superoxide anion release after prolonged infusion of lidocaine. J Pharmacol Exp
Ther 1985; 235: 418-22. 8. Rimback G, Cassuto J, Wallin G, Westlander G. Inhibition of peritonitis by amide local anesthetics. Anesthesiology 1988; 69: 881-86. 10. Cassuto J, Nellgård P, Stage L, Jonsson A. Amide local anesthetics reduce albumin extravasation in burn injuries. Anesthesiology 1990; 72: 302-07.
ADDRESSES Department of Anaesthesia and Intensive Care Unit (J Cassuto, MD, B Hanson, MD), and Department of Surgery (A Jonsson, MD), Central Hospital, Mölndal, Sweden. Correspondence to Dr J Cassuto, Department of Anaesthesia and Intensive Care Unit, Central Hospital, S-431 80 Molndal, Sweden