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Rhabdomyolysis After Correction of Hyponatremia Due to Psychogenic Polydipsia

1995; Elsevier BV; Volume: 70; Issue: 5 Linguagem: Inglês

10.4065/70.5.473

1942-5546

David A. Rizzieri,

Muscle and Compartmental Disorders

Severe neurologic complications resulting from correction of hyponatremia are common, but reports of nonneurologic sequelae are scarce. This article describes a patient in whom rhabdomyolysis developed during correction of severe hyponatremia attributable to psychogenic polydipsia. Relevant material about volume regulation in the cell is presented, and a potential mechanism of cell damage is proposed. This case report emphasizes the importance of monitoring for nonneurologic complications during correction of hyponatremia. Severe neurologic complications resulting from correction of hyponatremia are common, but reports of nonneurologic sequelae are scarce. This article describes a patient in whom rhabdomyolysis developed during correction of severe hyponatremia attributable to psychogenic polydipsia. Relevant material about volume regulation in the cell is presented, and a potential mechanism of cell damage is proposed. This case report emphasizes the importance of monitoring for nonneurologic complications during correction of hyponatremia. Psychogenic polydipsia is present in up to 17.5% of patients who are hospitalized for a lengthy duration because of mental illness, and severe hyponatremia develops in a fourth of such patients.1Blum A Tempey FW Lynch WJ Somatic Findings in patients with psychogenic polydipsia.J Clin Psychiatry. 1983; 44: 55-56PubMed Google Scholar Devastating neurologic complications including central pontine myelinolysis, cranial nerve palsies, coma, and death are associated with correction of severe hyponatremia. In this report, we describe a man with chronic schizophrenia who had severe hyponatremia attributable to psychogenic polydipsia. In the absence of other coexistent causative factors, rhabdomyolysis developed during correction of the patient's sodium concentration. This report emphasizes the importance of monitoring for nonneurologic complications during correction of hyponatremia. A 34-year-old man with paranoid schizophrenia sought medical attention because of an alteration in mental status. The patient's state of health had been as usual until the night of admission. His family noted progressive fatigue and irritability, and the patient complained of mild lightheadedness. He vomited a small amount of bilious material once before the current examination. He had no dry heaves. His parents had noted a substantial increase in his fluid intake during the prior 6 months and on the night of admission. He smoked one pack of cigarettes per day and drank 32 ounces of beer twice a week. Fluphenazine decanoate was his only medication, and the dose had been unchanged. He had no history of drug abuse, trauma, seizures, or environmental stressors or exposures. Physical examination revealed normal vital signs and no fever or orthostatic hypotension. An examination of the skin disclosed a truncal petechial rash that diminished during the first few days after admission. The patient was oriented but was fatigued and agitated. He was not combative, and no physical restraints were necessary at any time. He had no obvious active delusions, and he could name, repeat, read, and follow multiple-step commands. Sensory, motor, cranial nerve, and cerebellar function and reflexes were normal. Pertinent laboratory results are listed in Table 1. All electrolytes tested in the SMA 7/60 and 12/60 were normal, as was magnesium. The complete blood cell count, differential, and platelet count were within normal limits. Chest roentgenography, computed tomography, and lumbar puncture revealed no abnormalities. On admission, his urine was light yellow, and analysis revealed a specific gravity of 1.001; a trace of blood with 1 to 3 erythrocytes was noted on microscopic examination. A urine toxicology screen was positive only for phenothiazine medication, caffeine, and nicotine. No evidence of illicit drug use was present. Ethanol, isopropyl, and methanol levels were zero.Table 1Pertinent Lalwratory Values of Male Patient With Schizophrenia Who Had Severe Hyponatremia Due to Psychogenic PolydipsiaOsmolality (mOsm/kg of water)Time (h)Sodium (mEq/L)Correction rate (mEqA-/h)Chloride (mEq/L)Potassium (mEq/L)Creatine kinase (U/L)Lactate dehydrogenase (U/L)Aspartate transaminase (U/L)UrineSerum0110774.1395…………51171.4834.4………52…8124923.8……………201371.354.4…5,2081,898580…48137……5.1>40,0007,7652,865471…5 days141…1014.419,2505491,507……11 days………61722067……lyr137…………………… Open table in a new tab Psychogenic polydipsia was diagnosed. After the patient received 1 L of physiologic saline, fluid restriction was the only therapeutic method used. After initial improvement, he complained of generalized muscle aches 48 hours after admission, and his urine became dark brown. Urinalysis and serum evaluation (serum obtained at admission, frozen, and tested retrospectively) confirmed rhabdomyolysis (Table 1). His vital signs remained normal; he had no fever, and findings on physical examination remained unremarkable. All electrolyte levels tested in the SMA 7/60 and 12/60 were normal, as was the complete blood cell count. His medications had not been changed. The patient had been in a room where he could be carefully observed from the nursing station. The patient, staff, and family noted no intercurrent trauma or seizure activity. No intramuscular injections or physical restraints were necessary. No autonomic dysfunction or leukocytosis was noted. Fluid restriction was discontinued, and he intravenously received hydration. He did well and has had no further complications from rhabdomyolysis. Ten published case reports have described rhabdomyolysis associated with water intoxication2Browne PM Rhabdomyolysis and myoglobinuria associated with acute water intoxication.West J Med. 1979; 130: 459-461PubMed Google Scholar, 3Adler S Hyponatremia and rhabdomyolysis: a possible relationship.South Med J. 1980; 73: 511-513Crossref PubMed Scopus (35) Google Scholar, 4Morita S Scto M Hara K Ide Y Ishimaru T Izumi M et al.Case of acute water intoxication developing in a healthy adult.Nippon Naika Gakkai Zasshi. 1983; 72: 458-461Crossref PubMed Scopus (4) Google Scholar, 5Sidi Y Gassner S Sandbank U Keren G Pinkhas J Water intoxication, hyperpyrexia and rhabdomyolysis in a patient with psychogenic polydipsia.NY State J Med. 1984; 84: 462-464PubMed Google Scholar, 6Yonemura K Hishida A Miyajima H A case of water intoxication due to psychogenic polydipsia.Metab Dis (Jpn). 1984; 21: 1233-1238Google Scholar, 7Mor F Mor-Snir I Wysenbeek AJ Rhabdomyolysis in self-induced water intoxication.J Nerv Ment Dis. 1987; 175: 742-743Crossref PubMed Scopus (22) Google Scholar, 8Mitnick PD Bell S Rhabdomyolysis associated with severe hyponatremia after prostatic surgery.Am J Kidney Dis. 1990; 16: 73-75Abstract Full Text PDF PubMed Scopus (19) Google Scholar, 9Takehashi N Fukutake T Hirayama K Serum creatine kinase elevation due to water intoxication.Neurol Med. 1987; 27: 182-184Google Scholar, 10Tomiyama J Kametani H Kumagai Y Adachi Y Tohri K Water intoxication and rhabdomyolysis.Jpn J Med. 1990; 29: 52-55Crossref PubMed Scopus (17) Google Scholar, 11Putterman C Levy L Rubinger D Transient exercise-induced water intoxication and rhabdomyolysis.Am J Kidney Dis. 1993; 21: 206-209PubMed Scopus (37) Google Scholar (Table 2), only one of which involved psychogenic polydipsia in a mentally ill patient.6Yonemura K Hishida A Miyajima H A case of water intoxication due to psychogenic polydipsia.Metab Dis (Jpn). 1984; 21: 1233-1238Google Scholar All those reports had various confounding factors; thus, concluding that the hyponatremia, or its correction, was the proximate cause of the muscle damage is difficult. The current case is the only reported one that involves a mentally ill patient with severe hyponatremia attributable to psychogenic polydipsia in whom rhabdomyolysis developed after correction. The patient had no concomitant electrolyte abnormalities, signs of neuroleptic malignant syndrome, changes in medication or side effects, drug ingestion, or alcohol withdrawal. Additionally, he had· no seizures, trauma, environmental exposures, illnesses, or other known conditions associated with rhabdomyolysis, as reviewed by Gabow and associates in 1982.12Gabow PA Kaehny WD Kelleher SP The spectrum of rhabdomyolysis.Medicine. 1982; 61: 141-152Crossref PubMed Scopus (770) Google Scholar Thus, in the absence of other etiologic factors, the most likely cause of the muscle breakdown was the temporal relationship to correction of the electrolyte abnormality.Table 2Reported Cases of Water Intoxication Associated With Rhabdomyolysis*PP = psychogenic polydipsia; SIADH = syndrome of inappropriate antidiuretic hormone; WI -water intoxication.ReferenceDiagnosisSodium (mEq/L)Correction rate (mEq/L/h)Creatine kinase (U/L)Confounding variablesBrowne2Browne PM Rhabdomyolysis and myoglobinuria associated with acute water intoxication.West J Med. 1979; 130: 459-461PubMed Google ScholarWI1160.25–0.3598,000Exercise, mild hypokalemiaAdler3Adler S Hyponatremia and rhabdomyolysis: a possible relationship.South Med J. 1980; 73: 511-513Crossref PubMed Scopus (35) Google ScholarSIADH1071–2175,200Exercise-induced dystoniaMorita et al4Morita S Scto M Hara K Ide Y Ishimaru T Izumi M et al.Case of acute water intoxication developing in a healthy adult.Nippon Naika Gakkai Zasshi. 1983; 72: 458-461Crossref PubMed Scopus (4) Google ScholarWI124…1,815Convulsions, mild hyponatremiaSidi et al5Sidi Y Gassner S Sandbank U Keren G Pinkhas J Water intoxication, hyperpyrexia and rhabdomyolysis in a patient with psychogenic polydipsia.NY State J Med. 1984; 84: 462-464PubMed Google ScholarSIADH115…19,500Convulsions, mild hyponatremia. exercise, hyperthermia, acidosis. hypoxiaYonemura et al6Yonemura K Hishida A Miyajima H A case of water intoxication due to psychogenic polydipsia.Metab Dis (Jpn). 1984; 21: 1233-1238Google ScholarPP117…53,160Vomiting, hyperthermiaMor et al7Mor F Mor-Snir I Wysenbeek AJ Rhabdomyolysis in self-induced water intoxication.J Nerv Ment Dis. 1987; 175: 742-743Crossref PubMed Scopus (22) Google ScholarSIADH1190.55–0.601,531Found lying on ground, ? durationMitnick & Bell8Mitnick PD Bell S Rhabdomyolysis associated with severe hyponatremia after prostatic surgery.Am J Kidney Dis. 1990; 16: 73-75Abstract Full Text PDF PubMed Scopus (19) Google ScholarWI761.0–2.511,630Hypotensive event, hyperkalemiaTakehashi et al9Takehashi N Fukutake T Hirayama K Serum creatine kinase elevation due to water intoxication.Neurol Med. 1987; 27: 182-184Google ScholarWI119…14,400Convulsions, hypokalemiaTomiyama et al10Tomiyama J Kametani H Kumagai Y Adachi Y Tohri K Water intoxication and rhabdomyolysis.Jpn J Med. 1990; 29: 52-55Crossref PubMed Scopus (17) Google Scholar·SIADH1150.928,650Alcohol abuse, vomiting, mild hypokalemiaPutterman et al11Putterman C Levy L Rubinger D Transient exercise-induced water intoxication and rhabdomyolysis.Am J Kidney Dis. 1993; 21: 206-209PubMed Scopus (37) Google ScholarSIADH1150.55–0.6010,300Exercise, heat exposure, vomiting* PP = psychogenic polydipsia; SIADH = syndrome of inappropriate antidiuretic hormone; WI -water intoxication. Open table in a new tab Psychogenic polydipsia is found in up to 17.5% of patients who are hospitalized for a lengthy duration because of mental illness. Although severe hyponatremia due to polydipsia alone develops in only a small percentage of these patients, the consequences can be devastating. This population of patients has increased sensitivity to antidiuretic hormone and a lowered threshold for its release;13Goldman MB Luchins DJ Robertson GL Mechanisms of altered water metabolism in psychotic patients with polydip-sia and hyponatremia.N Engl J Med. 1988; 318: 397-403Crossref PubMed Scopus (264) Google Scholar however, the urine is still dilute (osmolality, less than 50 mOsm/kg). No standard long-term treatment exists for this disorder. Pharmacologic options including demeclocycline, propranolol, and clozapine have been tried, but, thus far, no large studies have proved their efficacy. Programs that involve modifying behavior in conjunction with weight monitoring and fluid restriction as needed, as well as rewarding behavior for maintaining weight, seem to be the most beneficial14McNally RJ Calamari JE Hansen PM Kaliher C Behavioral treatment of psychogenic polydipsia.J Behav Ther Exp Psychiatry. 1988; 19: 57-61Crossref PubMed Scopus (22) Google Scholar, 15Vieweg WV Godleski LS Polydipsia, water intoxication, and psychiatric illness [letter].J Behav Ther Exp Psychiatry. 1989; 20: 85-86Crossref PubMed Scopus (3) Google Scholar Our patient has done well as an outpatient, with close monitoring by his family and therapist, and readmission to a hospital has been unnecessary. The mechanism of muscle damage is still unclear but likely relates to failure in cell volume regulation. The patient's correction rate of 1.35 to 1.4 mEq/L per hour is within the range reported in numerous past series of 0.5 to more than 2.0 mEq/L per hour.16Stems RH Severe symptomatic hyponatremia: treatment and outcome; a study of 64 cases.Ann Intem Med. 1987; 107: 656-664Crossref PubMed Scopus (263) Google Scholar, 17Cluitmans FH Meinders AE Management of severe hyponatremia: rapid or slow correction?.Am J Med. 1990; 88: 161-166Abstract Full Text PDF PubMed Scopus (158) Google Scholar In water-stressed states, Na+-K+ and CI-HCO3− exchangers participate in cell volume regulation. Because of salt effects on enzymatic reactions and the Michaelis constant, their use as the primary homeostatic mechanism would severely limit the organism in its environmental tolerances. Types of life from all taxonomic categories seem to have surpassed this obstacle by depending on a few organic osmolytes that do not complex with the negatively charged cell metabolites and maintain a stable intracellular milieu, a situation that optimizes the cellular enzymatic functions.18Yancey PH Clark ME Hand SC Bowlus RD Somero GN Living with water stress: evolution of osmolyte systems.Science. 1982; 217: 1214-1222Crossref PubMed Scopus (3007) Google Scholar, 19Chamberlin ME Strange K Anisosmotic cell volume regulation: a comparative view.Am J Physiol. 1989; 257: C159-C173PubMed Google Scholar, 20Rymer MM Fishman RA Protective adaptation of brain to water intoxication.Arch Neurol. 1973; 28: 49-54Crossref PubMed Scopus (64) Google Scholar In blue crabs21Lang MA Correlation between osmoregulation and cell volume regulation.Am J Physiol. 1987; 252: R768-R773PubMed Google Scholar and barnacles,22Berman DM Pena-Rasgado C Holmgren M Hawkins P Rasgado-Flores H External Ca effect on water permeability, regulatory volume decrease, and extracellular space in barnacle muscle cells.Am I Physiol. 1993; 265: C1128-C1137PubMed Google Scholar muscle cells initially swell in hypo-osmotic environments, and sodium, potassium, and organic osmolytes have important roles in cell volume regulation. Research shows that skeletal muscles of rats in hyponatremic environs blunt cell swelling through the loss of osmolytes, particularly glutamine, glycine, and taurine.23Kamm D Sterns R Baer J Thomas D Rogers S Muscle osmolytes in hypo- and hypernatremia [abstract].J Am Soc Nephrol. 1993; 4: 296Google Scholar, 24Bedford JJ Leader JP Response of tissues of the rat to anisosmolality in vivo.Am J Physiol. 1993; 264: R1164-R1179PubMed Google Scholar No published studies have described changes in human muscle cell sodium, potassium, and organic osmolyte concentrations during the correction of hyponatremia. Regulatory mechanisms are highly conserved in phylogenetically diverse organisms, a suggestion that similar mechanisms are likely active in human muscle cells as well. Animal models have failed to reveal any histologic or pathologic evidence that hyponatremia itself causes any permanent deleterious effects.25Kleinschmidt-DeMasters BK Norenberg MD Neuropathologic observations in electrolyte-induced myelinolysis in the rat.J Neuropathol Exp Neurol. 1982; 41: 67-80Crossref PubMed Scopus (78) Google Scholar My colleagues and I hypothesize that cell volume regulatory mechanisms become overwhelmed during correction and allow the damage to occur. Many investigators believe that the rate of change is important in the development of these complications.16Stems RH Severe symptomatic hyponatremia: treatment and outcome; a study of 64 cases.Ann Intem Med. 1987; 107: 656-664Crossref PubMed Scopus (263) Google Scholar, 26Stems RH Severe hyponatremia: the case for conservative management.Crit Care Med. 1992; 20: 534-539Crossref PubMed Scopus (32) Google Scholar Why these regulatory mechanisms are occasionally inadequate to maintain a stable intracellular milieu during the correction phase of hyponatremia is speculative. Adjusting inorganic ion concentrations alters the Michaelis constant and the enzymatic functions in the cells. These changes may cause the osmolytes to become incompatible with the intracellular macromolecules, either by interfering with their functions or by causing complexes to be formed. This phenomenon may lead to membrane fragility and enzyme leakage. Additionally, the activation of inorganic ion channels for regulatory volume decreases may be calcium dependent22Berman DM Pena-Rasgado C Holmgren M Hawkins P Rasgado-Flores H External Ca effect on water permeability, regulatory volume decrease, and extracellular space in barnacle muscle cells.Am I Physiol. 1993; 265: C1128-C1137PubMed Google Scholar and changes in calcium concentrations may relate to the activity of second messenger systems that alter muscle cell membranes and allow the proposed enzyme leakage. Future research on changes in human muscle cell inorganic ion and organic osmolyte concentrations during correction of hyponatremia would be interesting and useful for further understanding about the nature of cell volume regulation and the inability of mechanisms to maintain homeostasis in response to certain environmental stressors. The current case report associates severe nonneurologic effects with correction of hyponatremia attributable to psychogenic polydipsia. The scope of debate and research must expand to consider these concerns. To my knowledge, this is the first report that associates rhabdomyolysis with the correction of isolated severe hyponatremia due to psychogenic polydipsia in a patient with a psychiatric disorder. Clinicians should be aware of the potential development of rhabdomyolysis during correction of hyponatremia.