Panic Attacks and Lactated Ringer’s Solution (1999)

Classified as a distinct entity with defined criteria [1], panic disorder affects 5% of the population and is diagnosed twice as frequently in women [2]. Pregnancy has no known effect on the disorder [3]. Although the neurobiological basis of panic disorder is unclear, sodium lactate has been used as a biologic marker and precipitant [4]. Because it contains lactate, lactated Ringer's solution has been avoided in patients with panic disorder [5]; we present this case to challenge that practice. Case Report A 30-yr-old, term, primiparous parturient presented in active labor. The patient had no allergies, took no medications, and denied any past or current medical or obstetrical problems. Concerned about labor and delivery pain, the patient spontaneously reported her anxiety as 4 of 10 (0 = the absence of anxiety) and requested epidural analgesia. With placement of an IV line, 1000 mL of lactated Ringer's solution was rapidly infused, an epidural catheter was placed, and a continuous infusion of local anesthetic was started. Anxiety level, which did not change with fluid administration, decreased to 2 of 10 with analgesia onset. Ten minutes after epidural placement, the patient's arterial blood pressure decreased from 114/60 to 104/60 mm Hg, and 10 mg of IV ephedrine with 500 mL of lactated Ringer's solution was given. Noting the chronotropic change, the patient reported her anxiety as 4 of 10. No additional hemodynamic or pharmacologic interventions (aside from the oxytocin augmentation of labor) were made for the duration of the labor, and anxiety scores remained 2-4 of 10 at each 60- to 90-min check for analgesia. The patient delivered uneventfully, having received 5 L of lactated Ringer's solution on removal of her IV catheter. Fifty hours after delivery, the patient reported a sense of impending doom, extreme anxiety of 9 of 10, and a desire for lorazepam and nortriptyline. Questioned about these medications and her ability to score anxiety, the patient admitted to a panic disorder history, which she had kept from her obstetric and anesthetic care team for fear of being treated differently. Contact with the patient's psychiatrist confirmed her Diagnostic and Statistical Manual of Mental Disorders diagnosis [3]; with restoration of treatment with lorazepam and nortriptyline, the patient returned to her baseline anxiety state (3 of 10) for the remainder of her hospital course. Discussion Common in women during the childbearing years [6], panic attack frequency is unchanged and increased during the gravid and postpartum states, respectively [7,8]. The observation of increased lactate levels in anxiety neurosis patients [9] led to its use as a provocative drug [10]; however, analyses [11,12] of 13 recent studies concluded that sodium lactate infusions were neither sensitive nor specific for panic disorders. Nonetheless, the amount of lactate in lactated Ringer's solution would be unlikely to precipitate an attack. A 1-mM solution of sodium lactate contains 1002 mEq/L sodium lactate [13]; sodium lactate regimens (1-mM solution at 5 mL/kg given over 20 min) require at least 12 min [12] to reach a serum lactate threshold of 12-15 mM/L [11] necessary to precipitate a panic attack. Thus, a 70-kg person would require 210 mL (approximately 210 mEq) of sodium lactate to trigger an attack; lactated Ringer's solution (28 mEq/L lactate) would require 7.5 L to produce this amount. Yet this volume of lactated Ringer's solution, even if rapidly administered, would be unable to reach the panic threshold because of the dilutional forces of the crystalloid itself. Moreover, lactate undergoes rapid metabolism and clearance via hepatic and renal oxidation, gluconeogenesis, and excretion [14]. Even when large quantities of lactated Ringer's solution are given to patients in shock, lactate is readily metabolized [15]. The mechanism by which sodium lactate produces panic attacks focuses on the complexing of calcium [10], despite the absence of serum levels or symptoms of hypocalcemia [16]. In the seminal study of sodium lactate in panic disorder, when an arbitrary amount of calcium (0.2 mM) was added, a decrease in anxiety symptoms was recorded (from 34.3% to 17.1%) [17]. Lactated Ringer's solution contains 3 mEq/L calcium, which represents a 0.02-mM solution. Although this concentration of calcium is 10 times less than the 0.2 mM used in the previous study, it may serve to further diminish the theoretical relationship between lactated Ringer's solution and panic attacks. The simultaneous administration of different calcium concentrations in the lactate model of panic disorders has not been investigated. Misdiagnosis is an unlikely explanation for why our patient did not experience a panic attack; the rigid diagnostic criteria used, her classic recurrence postpartum, and her resolution with treatment speak against this theory. More likely, the amount of lactate administered was insufficient to reach the minimal panic attack threshold. Consistent with our patient, should a panic attack occur, attention should be placed on psychological or emotional stressors [18], medications that mimic the symptoms or have a stronger potential relationship with panic disorders-i.e., chronotropic medications and oxytocin [19], respectively-the timing of the attack (postpartum), and other psychiatric disorders [20]. In summary, we present this case of a parturient with panic disorder that was not influenced by the use of lactated Ringer's solution. Although other fluid therapies may be readily available, we seriously question the avoidance of lactated Ringer's solution in patients with panic disorder.