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Acute Bilateral Compartment Syndrome Secondary to Polydipsia-Induced Severe Hyponatremia Catherine Girard-Martel 1, 2, Melanie Gagnon 1

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Acute Bilateral Compartment Syndrome Secondary to Polydipsia-Induced Severe Hyponatremia Catherine Girard-Martel 1, 2, Melanie Gagnon 1 Case Reports Acute Bilateral Compartment Syndrome Secondary to Polydipsia-Induced Severe Hyponatremia Catherine Girard-Martel 1, 2, Melanie Gagnon 1 Key Words: Compartment Syndrome, Hyponatremia, Primary Polydipsia, Psychogenic Polydipsia, Antipsychotics Introduction Case Report Acute compartment syndrome (ACS) occurs when the A 43-year-old male presented to the emergency depart- tissue pressure within a closed muscle compartment exceeds ment with episodes of falling without any specific trauma the perfusion pressure and results in muscle and nerve isch- to the legs and bilateral anterior leg pain over the preced- emia. ACS has an annual incidence of 3.1 per 100,000 and ing three days. His past medical history was significant predominantly affects young men under the age of 35 be- for schizophrenia, metabolic syndrome and mild anemia cause of their significant muscle mass (1). Bone fracture is secondary to hemorrhoids. Relevant medications included: the leading cause (75%) of ACS (1); however, several other olanzapine, sertraline, spironolactone/hydrochlorothiazide nontraumatic etiologies have also been reported, includ- and rosuvastatin. He had experienced dry mouth as a side ing: thrombosis, bleeding diatheses, anticoagulation lead- effect of his medications and had been drinking over 6L of ing to hemorrhage/hematoma, ischemia-reperfusion injury, water a day. Moreover, he had consumed approximately 4L surgical positioning, limb compression, extravasation of of beer a day in the three days prior to his emergency room intravenous fluids and drug injection (1). A few cases have visit. also been described in diabetic patients with poor glycemic He complained of bilateral leg pain without any visible control (2), and one case has been reported secondary to abnormalities on examination of both anterior tibial com- primary hypothyroidism and adrenal insufficiency (3). To partments. He was, however, unable to actively flex or dorsi- our knowledge, only two previous cases of ACS secondary flex both feet. Passive stretching of extensor muscles elicited to severe hyponatremia have been reported and both were severe pain. Neurologic exam demonstrated diffuse hypoes- patients with schizophrenia and primary polydipsia (4, 5). thesia of the feet without generalized muscle rigidity. Labo- The case we present is the first of its kind in North Amer- ratory testing revealed mild leucocytosis (18.6x109/L), ane- ica. Despite the rare progression to ACS, clinicians need to mia (93 g/L), severe hyponatremia (114 mmol/L), increased be aware of this possibility when seeing patients present- serum lactate (5.8 mmol/L), and a significantly elevated cre- ing with rhabdomyolysis in association with hyponatremia atine kinase level (9,068 UI/L). Given diagnostic concern for because treatment must be initiated promptly. ACS, a surgical consult was immediately obtained and in- tracompartmental pressures were measured at 100 and 120 1CIUSSS Saguenay, Quebec City, Canada mmHg, respectively, in both anterior tibial compartments. 2Foothills Medical Center-Critical Care, Calgary, Alberta, Canada Additionally, all other compartment pressures of the lower Address for correspondence: Dr. Catherine Girard-Martel, CIUSSS extremities were abnormal (>30 mmHg). Saguenay, 305 Rue Saint Vallier, Chicoutimi, QC, Canada, G7H 5H6 Emergent bilateral fasciotomies of all compartments of Phone: 418-541-1234, #3535; Fax: 418-541-1019; E-mail: [email protected] the lower extremities were performed as soon as the diagno- sis was confirmed. The patient’s hyponatremia resolved with Submitted: March 4, 2014; Revised: June 18, 2014; Accepted: November 17, 2014 water restriction alone and he did not develop renal insuf- ficiency as a complication of his rhabdomyolysis. Anemia Clinical Schizophrenia & Related Psychoses Winter 2018 • 197 Girard-Martel(5).indd 1 12/25/17 1:13 PM (left-hand page running head) A Rare Complication Related to Schizophrenia (right-hand page running head) Catherine Girard-Martel, Melanie Gagnon A Rare Complication Related to Schizophrenia worsened during hospitalization and upper and lower gas- Since the first described case in 1977, there have been trointestinal endoscopy revealed findings of portal hyper- several reports in the literature of patients with rhabdo- tensive gastropathy and bleeding from congested internal myolysis in association with hyponatremia (9). The patho- hemorrhoids, both of which were as a result of a new diag- genic mechanism causing the rhabdomyolysis in hypo- nosis of cirrhosis. Healing of the wounds required skin graft- natremia is controversial, but may involve abnormality of ing (see Figure 1) and took several months, but fortunately sodium:calcium exchange across the muscle cell, so that the patient recovered complete neuromuscular function. calcium accumulates intracellularly. When intracellular cal- cium ions reach a critical concentration, they activate neural Discussion proteases and lipases that serve to destroy the cell (10). In a retrospective study of 475 hospitalized patients with rhab- Patients in the two previously published cases also car- domyolysis at Johns Hopkins Hospital, myotoxins were the ried diagnoses of schizophrenia and primary polydipsia. In commonest cause, with illicit drugs/alcohol responsible for a prospective observational study from Canada, the preva- 34% of cases and prescribed drugs for 11% of cases. Antipsy- lence of polydipsia among an outpatient population with chotics (36%) were the most frequently prescribed class of chronic mental illnesses was 15.7% (14/89 patients) and drugs responsible for the cases of rhabdomyolysis, followed 90.4% of the polydipsia patients had a primary diagnosis of by statins (20%), SSRIs (15%) and zidovudine (13%) (11). schizophrenia (6). Patients with schizophrenia and primary Rhabdomyolysis is not a well-understood adverse effect of polydipsia may be at increased risk of hyponatremia when antipsychotic use, but proposed mechanisms suggest in- a superimposed cause of reduced water excretion is pres- volvement of serotoninergic and/or dopaminergic blockade ent, such as selective serotonin reuptake inhibitors (SSRIs), (12). In addition to the other causes of hyponatremia men- thiazide diuretics, increased alcohol intake and cirrhosis in tioned above, the increased risk of rhabdomyolysis associat- our case. The syndrome of inappropriate secretion of antidi- ed with antipsychotic medication use in these three patients uretic hormone (SIADH) can also coexist in schizophrenia. might explain their development of ACS. Several psychotropics can cause SIADH (antipsychotics, an- Along with our case, the two previous reported cases tidepressants, anxiolytics and SSRIs are some examples) (7) involved the anterior compartments of the legs. In fact, the but psychotic exacerbations have also been associated with anterior tibial compartment is the most frequently affected enhanced release of ADH in polydipsic schizophrenic pa- muscular compartment in ACS from all causes. It may be tients (8). Figure 1 Fasciotomy Wounds Two Months Later 198 • Clinical Schizophrenia & Related Psychoses Winter 2018 Girard-Martel(5).indd 2 12/25/17 1:13 PM (left-hand page running head) A Rare Complication Related to Schizophrenia (right-hand page running head) Catherine Girard-Martel, Melanie Gagnon Catherine Girard-Martel, Melanie Gagnon Figure 2 Physiopathological Hypothesis Underlying ACS in Severe Hyponatremia Severe hyponatremia Myotoxins (drugs, alcohol) Osmolality Can cause rhabdomyolsis Transfer of water Functional (osmotic balance) impairment of the limb Rhabdomyolsis Intracompartmental pressure Tissue necrosis Venous Vascular return permeability Alteration in Muscle and nerve arteriovenous ischemia (ACS) pressure gradient Capillary perfusion Cellular anoxia more common in the forearm and leg because the muscula- from any causes (secondary rhabdomyolysis), rhabdomy- ture is constrained by firm, well-defined fascial boundaries olysis infrequently leads to ACS. The patient’s rhabdomyoly- in a relatively limited anatomical space (13). Therefore, the sis was either associated with the hyponatremia at first, and anterior tibial compartment should be carefully evaluated then contributing to the development of ACS, or occurred in patients with symptoms and signs suggestive of ACS. In- later secondary to the ACS. In both possibilities, the rhabdo- terestingly, the patient we describe had a new diagnosis of myolysis was likely worsened by alcohol consumption and liver cirrhosis made during hospitalization. Although strong polypharmacy consisting of an antipsychotic, a statin, an evidence is lacking, according to a retrospective review by SSRI and a diuretic. Baek et al. (14) patients with cirrhosis who develop rhabdo- myolysis are at increased risk of recurrent rhabdomyolysis Conclusions and mortality compared to patients without liver disease. Physicians from several different medical specialties In our case, acute hyponatremia was probably the incit- (e.g., family and emergency physicians, internists and psy- ing event that led to the ACS. The physiopathology of hy- chiatrists) may encounter patients with nontraumatic causes ponatremia-induced compartment syndrome has not been of ACS. Patients with schizophrenia and polydipsia may be studied, but we propose that the acute decrease in blood particularly at risk. After six hours of the development of osmolality unbalances the osmotic state and promotes wa- ACS, complete functional recovery cannot be guaranteed, ter movement
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