93
Psychiatry Research. 32:93-94 Elsevier
Letter Lactate-Induced Panic and Beta-Adrenergic Blockade To the Editors: The sodium lactate infusion model has been frequently used to study the biological aspects of panic anxiety since the original report by Pitts and McClure in 1967. The mechanism of lactate-induced panic remains unclear. Some symptoms of panic disorder such as heart pounding, shortness of breath, tremulousness, and sweating suggest P-adrenergic activation. Some clinical studies also suggest that &blockers may be effective in the treatment of anxiety (Tyrer and Lader, 1974). However, Gorman et al. (1983) found that pretreatment with propranolol hydrochloride, a P-adrenergic blocking agent, did not prevent panic attacks, anxiety, and increases in heart rate and systolic blood pressure during lactate infusions. We report on a 27-year-old white female patient with a diagnosis of agoraphobia with panic attacks and a duration of illness of 6 months. She participated in a lactateinfusion study. Sodium lactate (6 ml/ kg) was administered as a I M solution in DSW. The infusion was administered with an IVAC variable pressure volumetric pump model 560 (San Diego, CA). Heart rate was recorded every I5 set and blood pressure every min during the procedure using a Hewlett Packard 78352-A patient monitor. Anxiety ratings were also obtained at regular intervals using a modified version of the Panic Description Scale (PDS), used in a previous study (Yeragani et al., 1989). The patient gradually became anxious during the first 4 min and then developed a severe panic attack, at which point the infusion was stopped 5 min and IO set after it was started. At this time the patient had an increase of I6 points on her PDS; six symptoms were rated as severe, and she described
Ol65-1781/90/$03.50
@ 1990 Elsevier Scientific
it as a very severe attack. Even after the infusion was stopped, the patient became increasingly anxious and started shaking severely. She reported that she has had severe shaking associated with her naturally occurring panic attacks in the past. Fig. I. presents the patient’s heart rate changes. The baseline heart rate was 72 (average of 4 readings a min), 103 during the Sth, I54 during the 6th, I78 during the 7th, 172 during the 8th, and I8 I during the 9th min. The maximum heart rate that was recorded during the l5-set intervals was 205 during the 8th min and 209 during the 9th min. These recordings appear to be reliable as the QRS complexes were clear on the screen of the monitor. At this
Fig. 1. Heart rate changes during sodium lactate infusion in female patient with agoraphobia and panic attacks
m. < 60. 0
5
TIME (minutes)
10
THROUGH
15
THE INFUSION
time, we decided to use propranolol to decrease the heart rate and I mg was given i.v. over 4-5 sec. The shaking disappeared in a few set and the patient appeared calmer within a min. The heart rate decreased to I36
Publishers Ireland
Ltd.
94
during the 10th min, 106 during the I I th, and 99 during the 12th min. There was a gradual decrease later. The patient had some subjective symptoms of anxiety, and the PDS reached baseline values around the 18th min; there was a decrease in the scores of both psychological and somatic symptoms of the PDS at this time. It is important to know that propranolol (about I mg i.v.) can be successfully used as a treatment if heart rate increases to very high levels during lactate infusions. In this report, the patient’s heart rate dropped from 209 (9th min) to 97 (during the 12th min), a difference of I I2 beats, after propranolol was given. This is interesting because in the study of Gorman et al. (1983) pretreatment with propranolol did not block the increases in heart rate during lactate infusions. It should be noted that though our patient did not appear to have any objective anxiety within I min of i.v. propranolol administration, her heart rate was still 64 beats higher than the baseline value. Even at the 12th min, the heart rate was still 27 beats higher than the baseline value. It is possible that the heart rate may have returned to normal values with a higher dose of propranolol. Though the symptoms of lactate-induced panic subside over time, the symptoms in this patient subsided quite promptly after the administration of propranolol. In our previous experience, heart rate had never reached such high levels after the lactate infusion ended. Though lactate-induced panic attacks are associated with sinus tachycardia and the cardiac rhythm of the patient appeared normal on the monitor, it is difficult to rule out the possibility of tachycardias such as a paroxysmal atrial tachycardia which would have responded to propranolol. This extreme increase of heart rate and anxiety even after the infusion was stopped may have been due to an unusual reaction of the patient to
lactate-induced panic and it is useful to know that propranolol can be used effectively in situations of autonomic changes during lactate-induced panic. On the other hand, propranolol may be useful in some cases to reverse the symptoms of lactate-induced panic once they have occurred, though it may not be able to prevent the occurrence of lactate-induced panic. This may also indicate that the role of the /3-adrenergic system in lactate-induced panic is not clear and that pretreatment may differ from treatment once symptoms have begun. References
Gorman, J.M.; Levy, G.F.; Liebowitz, M.R.; McGrath, P.; Appelby, I.L.; Dillon, D.J.; Davies, SO.; and Klein, D.F. Effect of acute beta-adrenergic blockade on lactate-induced panic. Archives of General Psychiatry, 40:1079-1082,
1983.
Pitts, F., and McClure, J. Lactate metabolism in anxiety neurosis. New England Journal of Medicine.
27: I328- 1336, 1967.
Tyrer, P., and Lader, M.H. Response to propranolol and diazepam in somatic and psychic anxiety. British Medical Journal, 2:14-16,
1974.
Yeragani, V.K.; Balon, R.; and Pohl, R. Lactate infusions in panic-disorder patients and normal controls: Autonomic measures and subjective anxiety. Acta Psychiatrica Scandinavica. 79:32-40, 1989. Vikram K. Yeragani, M.D. Robert Pohl, M.D. Richard Balon, M.D.
Lafayette Clinic 951 E. Lafayette Ave. Detroit, Ml 48207, USA Received Ma-v 26. 1989; revised August 1989; accepted November 18. 1989.
21,
Psychiatry Research. 32:93-94 Elsevier
Letter Lactate-Induced Panic and Beta-Adrenergic Blockade To the Editors: The sodium lactate infusion model has been frequently used to study the biological aspects of panic anxiety since the original report by Pitts and McClure in 1967. The mechanism of lactate-induced panic remains unclear. Some symptoms of panic disorder such as heart pounding, shortness of breath, tremulousness, and sweating suggest P-adrenergic activation. Some clinical studies also suggest that &blockers may be effective in the treatment of anxiety (Tyrer and Lader, 1974). However, Gorman et al. (1983) found that pretreatment with propranolol hydrochloride, a P-adrenergic blocking agent, did not prevent panic attacks, anxiety, and increases in heart rate and systolic blood pressure during lactate infusions. We report on a 27-year-old white female patient with a diagnosis of agoraphobia with panic attacks and a duration of illness of 6 months. She participated in a lactateinfusion study. Sodium lactate (6 ml/ kg) was administered as a I M solution in DSW. The infusion was administered with an IVAC variable pressure volumetric pump model 560 (San Diego, CA). Heart rate was recorded every I5 set and blood pressure every min during the procedure using a Hewlett Packard 78352-A patient monitor. Anxiety ratings were also obtained at regular intervals using a modified version of the Panic Description Scale (PDS), used in a previous study (Yeragani et al., 1989). The patient gradually became anxious during the first 4 min and then developed a severe panic attack, at which point the infusion was stopped 5 min and IO set after it was started. At this time the patient had an increase of I6 points on her PDS; six symptoms were rated as severe, and she described
Ol65-1781/90/$03.50
@ 1990 Elsevier Scientific
it as a very severe attack. Even after the infusion was stopped, the patient became increasingly anxious and started shaking severely. She reported that she has had severe shaking associated with her naturally occurring panic attacks in the past. Fig. I. presents the patient’s heart rate changes. The baseline heart rate was 72 (average of 4 readings a min), 103 during the Sth, I54 during the 6th, I78 during the 7th, 172 during the 8th, and I8 I during the 9th min. The maximum heart rate that was recorded during the l5-set intervals was 205 during the 8th min and 209 during the 9th min. These recordings appear to be reliable as the QRS complexes were clear on the screen of the monitor. At this
Fig. 1. Heart rate changes during sodium lactate infusion in female patient with agoraphobia and panic attacks
m. < 60. 0
5
TIME (minutes)
10
THROUGH
15
THE INFUSION
time, we decided to use propranolol to decrease the heart rate and I mg was given i.v. over 4-5 sec. The shaking disappeared in a few set and the patient appeared calmer within a min. The heart rate decreased to I36
Publishers Ireland
Ltd.
94
during the 10th min, 106 during the I I th, and 99 during the 12th min. There was a gradual decrease later. The patient had some subjective symptoms of anxiety, and the PDS reached baseline values around the 18th min; there was a decrease in the scores of both psychological and somatic symptoms of the PDS at this time. It is important to know that propranolol (about I mg i.v.) can be successfully used as a treatment if heart rate increases to very high levels during lactate infusions. In this report, the patient’s heart rate dropped from 209 (9th min) to 97 (during the 12th min), a difference of I I2 beats, after propranolol was given. This is interesting because in the study of Gorman et al. (1983) pretreatment with propranolol did not block the increases in heart rate during lactate infusions. It should be noted that though our patient did not appear to have any objective anxiety within I min of i.v. propranolol administration, her heart rate was still 64 beats higher than the baseline value. Even at the 12th min, the heart rate was still 27 beats higher than the baseline value. It is possible that the heart rate may have returned to normal values with a higher dose of propranolol. Though the symptoms of lactate-induced panic subside over time, the symptoms in this patient subsided quite promptly after the administration of propranolol. In our previous experience, heart rate had never reached such high levels after the lactate infusion ended. Though lactate-induced panic attacks are associated with sinus tachycardia and the cardiac rhythm of the patient appeared normal on the monitor, it is difficult to rule out the possibility of tachycardias such as a paroxysmal atrial tachycardia which would have responded to propranolol. This extreme increase of heart rate and anxiety even after the infusion was stopped may have been due to an unusual reaction of the patient to
lactate-induced panic and it is useful to know that propranolol can be used effectively in situations of autonomic changes during lactate-induced panic. On the other hand, propranolol may be useful in some cases to reverse the symptoms of lactate-induced panic once they have occurred, though it may not be able to prevent the occurrence of lactate-induced panic. This may also indicate that the role of the /3-adrenergic system in lactate-induced panic is not clear and that pretreatment may differ from treatment once symptoms have begun. References
Gorman, J.M.; Levy, G.F.; Liebowitz, M.R.; McGrath, P.; Appelby, I.L.; Dillon, D.J.; Davies, SO.; and Klein, D.F. Effect of acute beta-adrenergic blockade on lactate-induced panic. Archives of General Psychiatry, 40:1079-1082,
1983.
Pitts, F., and McClure, J. Lactate metabolism in anxiety neurosis. New England Journal of Medicine.
27: I328- 1336, 1967.
Tyrer, P., and Lader, M.H. Response to propranolol and diazepam in somatic and psychic anxiety. British Medical Journal, 2:14-16,
1974.
Yeragani, V.K.; Balon, R.; and Pohl, R. Lactate infusions in panic-disorder patients and normal controls: Autonomic measures and subjective anxiety. Acta Psychiatrica Scandinavica. 79:32-40, 1989. Vikram K. Yeragani, M.D. Robert Pohl, M.D. Richard Balon, M.D.
Lafayette Clinic 951 E. Lafayette Ave. Detroit, Ml 48207, USA Received Ma-v 26. 1989; revised August 1989; accepted November 18. 1989.
21,
