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DOI: 10.1055/a-1589-6049
Comparison of Sodium Lactate Infusion and Carbon Dioxide Inhalation Panic Provocation Tests: A Meta-analysis
Abstract
Background Sodium lactate (NaL) infusion and carbon dioxide (CO2) inhalation are proven to provoke acute panic attacks (PAs) in patients with panic disorder (PD). A systematic literature search and meta-analysis were performed to compare the effect sizes of these methods.
Methods Odds ratios were calculated for each of the original studies and were pooled using the random-effects model.
Results Either NaL or CO2 provocations significantly increased the rates of PAs in individuals with PD compared to those in healthy controls. However, the effect size of NaL infusion (OR=25.13, 95% CI=15.48–40.80) was significantly greater than that of CO2 inhalation (OR=10.58, 95%CI=7.88–14.21).
Conclusion The evidence for the efficacy of the two panic provocation tests is very strong. Yet, the results support the superiority of NaL infusion over CO2 inhalation challenge as a panic provocation test. Thus, lactate seems a much stronger stimulus than CO2 for the brain suffocation detector.
Publication History
Received: 20 April 2021
Accepted: 16 June 2021
Article published online:
19 October 2021
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
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References
-
1
American Psychiatric Association.
Diagnostic and Statistical Manual of Mental Disorders. 5. Aufl. Washington, DC:
American Psychiatric Association, 2013; https://www.psychiatry.org/psychiatrists/practice/dsm
- 2 Griez E, Schruers K. Experimental pathophysiology of panic. J Psychosom Res 1998; 45: 493-503 DOI: 10.1016/s0022-3999(98)00027-0;. PMID: 9859852
- 3 Klein DF. False suffocation alarms, spontaneous panics, and related conditions. An integrative hypothesis. Arch Gen Psychiatry 1993; 50: 306-317 DOI: 10.1001/archpsyc.1993.01820160076009.
- 4 Liebowitz MR, Fyer AJ, Gorman JM. et al. Lactate provocation of panic attacks. I. Clinical and behavioral findings. Arch Gen Psychiatry 1984; 41: 764-770
- 5 Stewart RS, Devous MD, Rush JA. et al. Cerebral blood flow changes during sodium-lactate-induced panic attacks. Am J Psychiatry 1988; 145: 442-449 DOI: 10.1176/ajp.145.4.442. PMID: 3258132.
- 6 Fyer AJ, Gorman JM, Liebowitz MR. et al. Sodium lactate infusion, panic attacks, and ionized calcium. Biol Psychiatry 1984; 19: 1437-1447. http://www.ncbi.nlm.nih.gov/pubmed/6518201
- 7 Fyer MR, Uy J, Martinez J. et al. CO2 challenge of patients with panic disorder. Am J Psychiatry 1987; 144: 1080-1082. http://psychiatryonline.org/doi/abs/10.1176/ajp.144.8.1080
- 8 Gorman JM, Papp LA, Martinez J. et al. High-dose carbon dioxide challenge test in anxiety disorder patients. Biol Psychiatry 1990; 28: 743-757. https://linkinghub.elsevier.com/retrieve/pii/0006322390905109
- 9 Perna G, Battaglia M, Garberi A. et al. Carbon dioxide/oxygen challenge test in panic disorder. Psychiatry Res 1994; 52: 159-171
- 10 Perna G, Gabriele A, Caldirola D. et al. Hypersensitivity to inhalation of carbon dioxide and panic attacks. Psychiatry Res 1995; 57: 267-273. https://linkinghub.elsevier.com/retrieve/pii/016517819502723A
- 11 Perna G, Barbini B, Cocchi S. et al. 35% CO2 challenge in panic and mood disorders. J Affect Disord 1995; 33: 189-194
- 12 Woods SW, Charney DS, Loke J. et al. Carbon dioxide sensitivity in panic anxiety. Ventilatory and anxiogenic response to carbon dioxide in healthy subjects and patients with panic anxiety before and after alprazolam treatment. Arch Gen Psychiatry 1986; 43: 900-909
- 13 Woods SW, Charney DS, Goodman WK. et al. Carbon dioxide-induced anxiety. Behavioral, physiologic, and biochemical effects of carbon dioxide in patients with panic disorders and healthy subjects. Arch Gen Psychiatry 1988; 45: 43-52
-
14
Panksepp J.
Affective neuroscience: The foundations of human and animal emotions (Series in
Affective Science). New York: Oxford University Press, 2004
-
15
Damasio AR.
The feeling of what happens: Body and emotion in the making of consciousness.
1st ed. Orlando: Harcourt, 1999
- 16 Moher D, Liberati A, Tetzlaff J. et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. J Clin Epidemiol 2009; 62: 1006-1012
-
17 StataCorp. Stata Statistical Software: Release 14. 2015; www.stata.com
-
18 R Core Team. R: A Language and Environment for Statistical Computing.
2019; https://www.r-project.org
-
19
Higgins JP,
Green S.
Assessing Risk of Bias in Included Studies. Version 5. The Cochrane
Collaboration, 2011; www.handbook.cochrane.org
- 20 Leth H, Toft P, Peitersen B. et al. Use of brain lactate levels to predict outcome after perinatal asphyxia. Acta Paediatr 1996; 85: 859-864. http://doi.wiley.com/10.1111/j.1651-2227.1996.tb14168.x
- 21 Kent JM, Papp LA, Martinez JM. et al. Specificity of panic response to CO2 inhalation in panic disorder: A comparison with major depression and premenstrual dysphoric disorder. Am J Psychiatry 2001; 158: 58-67
- 22 Gorman JM, Papp LA, Coplan JD. et al. Anxiogenic effects of CO2 and hyperventilation in patients with panic disorder. Am J Psychiatry 1994; 151: 547-553
- 23 Liebowitz MR, Gorman JM, Fyer A. et al. Possible mechanisms for lactate’s induction of panic. Am J Psychiatry 1986; 143: 495-502. http://psychiatryonline.org/doi/abs/10.1176/ajp.143.4.495
- 24 Vollmer LL, Ghosal S, McGuire JL. et al. Microglial acid sensing regulates carbon dioxide-evoked fear. Biol Psychiatry 2016; 80: 541-551. https://linkinghub.elsevier.com/retrieve/pii/S0006322316323782
- 25 Gorman JM, Goetz RR, Dillon D. et al. Sodium D-lactate infusion of panic disorder patients. Neuropsychopharmacology 1990; 3: 181-189
- 26 Wemmie JA, Askwith CC, Lamani E. et al. Acid-sensing ion channel 1 Is localized in brain regions with high synaptic density and contributes to fear conditioning. J Neurosci 2003; 23: 5496-5502
- 27 Guyatt G, Oxman AD, Akl EA. et al. GRADE guidelines: 1. Introduction—GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011; 64: 383-394. https://linkinghub.elsevier.com/retrieve/pii/S0895435610003306
- 28 Aronson TA, Carasiti I, McBane D. et al. Biological correlates of lactate sensitivity in panic disorder. Biol Psychiatry 1989; 26: 463-477
- 29 Bisaga A, Katz JL, Antonini A. et al. Cerebral glucose metabolism in women with panic disorder. Am J Psychiatry 1998; 155: 1178-1183
- 30 Coplan JD, Goetz RR, Klein DF. et al. Plasma cortisol concentrations preceding lactate-induced panic. Arch Gen Psychiatry 1998; 55: 130-136
- 31 Dager SR, Marro KI, Richards TL. et al. Preliminary application of magnetic resonance spectroscopy to investigate lactate-induced panic. Spectroscopy 1994; 151: 57-63
- 32 Dager SR, Richards T, Strauss W. et al. Single-voxel 1H-MRS investigation of brain metabolic changes during lactate-induced panic. Psychiatry Res 1997; 76: 89-99
- 33 Dager SR, Friedman SD, Heide A. et al. Two-dimensional proton echo-planar spectroscopic imaging of brain metabolic changes during lactate-induced panic. Arch Gen Psychiatry 1999; 56: 70-77
- 34 Dillon DJ, Gorman JM, Liebowitz MR. et al. Measurement of lactate-induced panic and anxiety. Psychiatry Res 1987; 20: 97-105
- 35 Ehlers A, Margraf J, Roth WT. et al. Lactate infusions and panic attacks: Do patients and controls respond differently?. Psychiatry Res 1986; 17: 295-308
- 36 Facchinetti F, Romano G, Fava M. et al. Lactate infusion induces panic attacks in patients with premenstrual syndrome. Psychosom Med 1992; 54: 288-296
- 37 George DT, Nutt DJ, Waxman RP. et al. Panic response to lactate administration in alcoholic and nonalcoholic patients with panic disorder. Am J Psychiatry 1989; 146: 1161-1665
- 38 George DT, Lindquist T, Nutt DJ. et al. Effect of chloride or glucose on the incidence of lactate-induced panic attacks. Am J Psychiatry 1995; 152: 692-697
- 39 Gorman JM, Davies M, Steinman R. et al. An objective marker of lactate-induced panic. Psychiatry Res 1987; 22: 341-348
- 40 Gorman JM, Fyer MR, Goetz RR. et al. Ventilatory physiology of patients with panic disorder. Arch Gen Psychiatry 1988; 45: 31-39
- 41 Hollander E, Liebowitz MR, Cohen B. et al. Prolactin and sodium lactate-induced panic. Psychiatry Res 1989; 28: 181-191
- 42 Jensen CF, Keller TW, Peskind ER. et al. Behavioral and plasma cortisol responses to sodium lactate infusion in posttraumatic stress disorder. Ann N Y Acad Sci 1997; 821: 444-448. http://www.ncbi.nlm.nih.gov/pubmed/9238226
- 43 Kellner M, Herzog L, Yassouridis A. et al. Possible role of atrial natriuretic hormone in pituitary-adrenocortical unresponsiveness in lactate-induced panic. Am J Psychiatry 1995; 152: 1365-1367
- 44 Kellner M, Knaudt K, Jahn H. et al. Atrial natriuretic hormone in lactate-induced panic attacks: Mode of release and endocrine and pathophysiological consequences. J Psychiatr Res 1998; 32: 37-48
- 45 Levin AP, Doran AR, Liebowitz MR. et al. Pituitary adrenocortical unresponsiveness in lactate-induced panic. Psychiatry Res 1987; 21: 23-32
- 46 Otte C, Kellner M, Arlt J. et al. Prolactin but not ACTH increases during sodium lactate-induced panic attacks. Psychiatry Res 2002; 109: 201-205. https://linkinghub.elsevier.com/retrieve/pii/S0165178102000148
- 47 Papp LA, Martinez JM, Klein DF. et al. Arterial blood gas changes in panic disorder and lactate-induced panic. Psychiatry Res 1989; 28: 171-180
- 48 Peskind ER, Jensen CF, Pascualy M. et al. Sodium lactate and hypertonic sodium chloride induce equivalent panic incidence, panic symptoms, and hypernatremia in panic disorder. Biol Psychiatry 1998; 44: 1007-1016
- 49 Plag J, Gaudlitz K, Zschucke E. et al. Distinct panicogenic activity of sodium lactate and cholecystokinin tetrapeptide in patients with panic disorder. Curr Pharm Des 2012; 18: 5619-5626. http://www.eurekaselect.com/openurl/content.php?genre=article&issn=1381-6128&volume=18&issue=35&spage=5619
- 50 Seier FE, Kellner M, Yassouridis A. et al. Autonomic reactivity and hormonal secretion in lactate-induced panic attacks. Am J Physiol Circ Physiol 1997; 272: H2630-H2638. https://www.physiology.org/doi/10.1152/ajpheart.1997.272.6.H2630
- 51 Sloan EP, Natarajan M, Baker B. et al. Nocturnal and daytime panic attacks comparison of sleep architecture, heart rate variability, and response to sodium lactate challenge. Biol Psychiatry 1999; 45: 1313-1320
- 52 Targum SD. Differential responses to anxiogenic challenge studies in patients with major depressive disorder and panic disorder. Biol Psychiatry 1990; 28: 21-34
- 53 Targum SD. Panic attack frequency and vulnerability to anxiogenic challenge studies. Psychiatry Res 1991; 36: 75-83
- 54 Alkın T, Tural Ü, Onur E. et al. Basilar artery blood flow velocity changes in patients with panic disorder following 35% carbon dioxide challenge. Prog Neuro-Psychopharmacology. Biol Psychiatry 2007; 31: 115-122. https://linkinghub.elsevier.com/retrieve/pii/S027858460600323X
- 55 Antony MM, Brown TA, Barlow DH. Response to hyperventilation and 5.5% CO2 inhalation of subjects with types of specific phobia, panic disorder, or no mental disorder. Am J Psychiatry 1997; 154: 1089-1095
- 56 Atlı Ö, Bayın M, Alkın T. Hypersensitivity to 35% carbon dioxide in patients with adult separation anxiety disorder. J Affect Disord 2012; 141: 315-323. https://linkinghub.elsevier.com/retrieve/pii/S0165032712002285
- 57 Berzak E, Reznik M, Narsia O. et al. Sensitivity to carbon dioxide in subjects with a single lifetime panic attack: Possible clinical ?bedside? predictive test for panic disorder after a first attack. Depress Anxiety 2004; 20: 48-50. http://doi.wiley.com/10.1002/da.20025
- 58 Blechert J, Wilhelm FH, Meuret AE. et al. Respiratory, autonomic, and experiential responses to repeated inhalations of 20% CO2 enriched air in panic disorder, social phobia, and healthy controls. Biol Psychol 2010; 84: 104-111. https://linkinghub.elsevier.com/retrieve/pii/S0301051110000050
- 59 Bocola V, Trecco M, Fabbrini G. et al. Antipanic effect of fluoxetine measured by CO2 challenge test. Biol Psychiatry 1998; 43: 612-615. https://linkinghub.elsevier.com/retrieve/pii/S0006322397002217
- 60 Caldirola D, Perna G, Arancio C. et al. The 35% CO2 challenge test in patients with social phobia. Psychiatry Res 1997; 71: 41-48
- 61 Goetz RR, Klein DF, Papp LA. et al. Acute panic inventory symptoms during CO2 inhalation and room-air hyperventilation among panic disorder patients and normal controls. Depress Anxiety. 2001. 14. 123-136 http://doi.wiley.com/10.1002/da.1054
- 62 Gorman JM, Martinez J, Coplan JD. et al. The effect of successful treatment on the emotional and physiological response to carbon dioxide inhalation in patients with panic disorder. Biol Psychiatry 2004; 56: 862-867. https://linkinghub.elsevier.com/retrieve/pii/S0006322304009035
- 63 Griez EJL, Lousberg H, van den Hout MA. CO2 vulnerability in panic disorder. Psychiatry Res 1987; 20: 87-95. https://linkinghub.elsevier.com/retrieve/pii/0165178187900011
- 64 Holt PE, Andrews G. Provocation of panic: Three elements of the panic reaction in four anxiety disorders. Behav Res Ther 1989; 27: 253-261
- 65 Monkul ES, Onur E, Tural Ü. et al. History of suffocation, state-trait anxiety, and anxiety sensitivity in predicting 35% carbon dioxide-induced panic. Psychiatry Res 2010; 179: 194-197. https://linkinghub.elsevier.com/retrieve/pii/S016517810900239X
- 66 Niccolai V, van Duinen MA, Griez EJ. Objective and subjective measures in recovery from a 35% carbon dioxide challenge. Can J Psychiatry 2008; 53: 737-744. http://journals.sagepub.com/ DOI: 10.1177/070674370805301105.
- 67 Papp LA, Klein DF, Martinez J. et al. Diagnostic and substance specificity of carbon-dioxide-induced panic. Am J Psychiatry 1993; 150: 250-257. http://psychiatryonline.org/doi/abs/10.1176/ajp.150.2.250
- 68 Papp LA, Martinez JM, Klein DF. et al. Respiratory psychophysiology of panic disorder: Three respiratory challenges in 98 subjects. Am J Psychiatry 1997; 154: 1557-1565. http://www.ncbi.nlm.nih.gov/pubmed/9356564
- 69 Perna G, Bertani A, Arancio C. et al. Laboratory response of patients with panic and obsessive-compulsive disorders to 35% CO2 challenges. Am J Psychiatry 1995; 152: 85-89
- 70 Perna G, Brambilla F, Arancio C. et al. Menstrual cycle-related sensitivity to 35% CO2 in panic patients. Biol Psychiatry 1995; 37: 528-532. https://linkinghub.elsevier.com/retrieve/pii/000632239400154U
- 71 Perna G, Cocchi S, Bertani A. et al. Sensitivity to 35% CO2 in healthy first-degree relatives of patients with panic disorder. Am J Psychiatry 1995; 152: 623-625. http://psychiatryonline.org/doi/abs/10.1176/ajp.152.4.623
- 72 Perna G, Bussi R, Allevi L. et al. Sensitivity to 35% carbon dioxide in patients with generalized anxiety disorder. J Clin Psychiatry 1999; 60: 379-384. http://article.psychiatrist.com/?ContentType=START&ID=10002426
- 73 Perna G, Casolari A, Bussi R. et al. Comparison of 35% carbon dioxide reactivity between panic disorder and eating disorder. Psychiatry Res 2004; 125: 277-283. https://linkinghub.elsevier.com/retrieve/pii/S0165178104000046
- 74 Ponto LLB, Kathol RG, Kettelkamp R. et al. Global cerebral blood flow after CO2 inhalation in normal subjects and patients with panic disorder determined with [15O]water and PET. J Anxiety Disord 2002; 16: 247-258. https://linkinghub.elsevier.com/retrieve/pii/S0887618502000944
- 75 Rapee RM, Brown TA, Antony MM. et al. Response to hyperventilation and inhalation of 5.5% carbon dioxide-enriched air across the DSM-III-R anxiety disorders. J Abnorm Psychol 1992; 101: 538-552
- 76 Rassovsky Y, Abrams K, Kushner MG. Suffocation and respiratory responses to carbon dioxide and breath holding challenges in individuals with panic disorder. J Psychosom Res 2006; 60: 291-298. https://linkinghub.elsevier.com/retrieve/pii/S0022399905003090
- 77 Sasaki I, Akiyoshi J, Sakurai R. et al. Carbon dioxide induced panic attack in panic disorder in Japan. Prog Neuropsychopharmacol Biol Psychiatry 1996; 20: 1145-1157
- 78 Schutters SI, Viechtbauer W, Knuts IJ. et al. 35% CO2 sensitivity in social anxiety disorder. J Psychopharmacol 2012; 26: 479-486. http://journals.sagepub.com/ DOI: 10.1177/0269881111430750.
- 79 van Duinen MA, Schruers KRJ, Maes M. et al. CO2 challenge induced HPA axis activation in panic. Int J Neuropsychopharmacol 2007; 10: 797-804. https://academic.oup.com/ijnp/article-lookup/ DOI: 10.1017/S1461145706007358.
- 80 van den Hout MA, van der Molen GM, Griez E. et al. Reduction of CO2-induced anxiety in patients with panic attacks after repeated CO2exposure. Am J Psychiatry 1987; 144: 788-791
- 81 Woznica A, Vickers K, Koerner N. et al. Reactivity to 35% carbon dioxide in bulimia nervosa and panic disorder. Psychiatry Res 2015; 228: 571-575. https://linkinghub.elsevier.com/retrieve/pii/S0165178115003376