Case report and Psychiatry Research 2017;53:147-154 DOI: 10.20471/dec.2017.53.02.05 Received October 11, 2017, accepted after revision October 21, 2017

Severe and Intoxication – Diagnostic Challenge in Department of Emergency Medicine

Jure Pupić-Bakrač1, Jeremije Radović1, Ana Pupić-Bakrač2, Dino Markota3, Dušan Pupić-Bakrač4 1Department of Emergency Medicine, University Clinical Hospital Mostar, Bosnia and Herzegovina, 2Department of Ophthalmology, General hospital Zadar, Croatia,3 Depart- ment of Internal Medicine, University Clinical Hospital Mostar, Bosnia and Herzegovina, 4Sanus Medical Group, Zadar, Croatia

Abstract - Psychogenic is a disorder characterized by compulsive of water in a popula- tion of psychiatric patients, most often those suffering from chronic psychosis. It can lead to severe dilutional hyponatremia and , which is manifested by and associated neurological symptomatology. A 43 years-old patient was admitted to the Department of Emergency Medicine due to con- vulsions of the right hand and leg, which began one hour before arrival. During the episode, the patient was conscious, vomited once and had urinary incontinence. In the medical history he had epilepsy, chronic psy- chosis and moderate mental retardation. Vital parameters were stable, and physical examination did not re- veal any associated pathological signs. Samples for laboratory analysis were taken and therapy with infusions of Diasepam (20 mg) included, to which patient was resistant. By heteroanamnesis it was acknowledged that in the last few days he spent more time than usual . Reviewing laboratory results it was found out that sodium concentration was 98 mmol/L. We began the gradual correction of sodium, after which the patient reached the full extent of recovery. Water intoxication is an emergency condition that is in clinical practice often mistaken for other neurological and internal emergency states, because of its non-specific symptomatology. With timely diagnosis and application of adequate treatment, recovery is complete. Keywords: polydipsia, psychogenic; hyponatremia; water intoxication

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Introduction Hyponatremia is the most common elec- trolyte imbalance, and is defined as the so- dium concentration below 135 mmol / L. Correspondence to: Jure Pupić-Bakrač, Department of It is classified as mild (130-134 mmol / L), Emergency Medicine, University Clinical Hospital Mostar, Bijeli Brijeg bb, 88 000 Mostar, Bosnia moderate (125-129 mmol / L), severe (120- and Herzegovina 124 mmol / L) and extremely severe (<120 Telephone: +385989764788 E-mail: [email protected] mmol / L) [1]. Etiologically, many factors 148 may be the cause of hyponatremia, and some psychopharmacs, alcoholism, mental retarda- of the most common are heart, kidney and tion, poor anamnesis) that can initially mis- liver diseases, inappropriate antidiuretic hor- lead the clinician. Early detection and treat- mone syndrome, certain drugs, vomiting and ment of water intoxication can save life. diarrhea, increased water intake, , consumption of ecstasy, etc. [2]. Case presentation Increased water intake (polydipsia) is a A 43-year-old patient was admitted to the factor that can cause severe dilutional hypo- Department of Emergency Medicine for a natremia and consequently water intoxica- convulsive episode. According to the report tion. Water intoxication is a life-threatening of the nurse accompanying the patient, one condition due to the decrease of serum os- hour prior to arrival he continuously began to molality and the diffusion of water into the spasm his right hand, leg and right side of the intracellular space, which is primarily mani- face. He was conscious and verbally commu- fested by brain edema. Symptomatology de- nicative the whole time during the episode. pends on serum sodium levels and the speed He vomited once and had urinary inconti- of hyponatremia development. It includes nence. He did not suffer head trauma nor was the following symptoms and signs: nausea, febrile in the past period. vomiting, headache, confusion, fatigue, agi- From the medical history, it was learned tation, hypotonia, convulsions, coma and that the patient was suffering from chronic ultimately death. The neurological deficit in psychosis and moderate mental retardation, most cases progresses proportionally to the for which he was permanently situated in the severity of sodium deficit. Lethal outcome facility for adults with special needs. Also, he is the consequence of increased intracranial had recorded epileptic seizures and was on pressure and herniation of cerebellar tonsils antiepileptic therapy. He has been treated for below foramen magnum [3]. hypertension, and in the last 6 months for Polydipsia is a condition that can be recurrence of tuberculosis. The therapy con- caused by various factors, for example endur- sisted of: Carbamazepine tbl. a 200 mg 1x1, ance sports, overhydration in heat, attempt Sodium valproate tbl. a 300 mg 2x2, Halo- to conceal doping abuse, water abuse, water peridol tbl. a 5 mg 1 + 1 + 2, Promazine tbl. diet, drug induced polydipsia etc. [4]. A spe- a 100 mg 1 + 1 + 1.5, Diasepam tbl. a 5 mg cial subset of polydipsia is psychogenic poly- 3x1, Biperiden hydrochloride tbl. a 2 mg 1x1, dipsia, characterized by compulsive - Lisinopril tbl. a 10 mg 1x1, Amoxicillin caps. ing of water in a population of psychiatric a 500 mg 3x1, and antituberculous therapy patients, most often those suffering from according to the protocol for recurrence psychosis [5]. At the Department of Emer- (Streptomycin amp. a 750 mg 1x1 i.m – for gency Medicine, water intoxication can be a first two months, Isoniazid tbl. a 75 mg 1x4 + major diagnostic challenge, especially in the Rifampicin tbl. a 150 mg 1x4 + Pyrazinamide sense of differential diagnosis versus neuro- tbl. a 400 mg 1x4 + Ethambutol tbl. a 275 mg logical conditions such as epilepsy. Psychiat- 1x4 – for first three months; Isoniazid tbl. a ric diagnoses are often associated with other 75 mg 1x4 + Rifampicin tbl. a 150 mg 1x4 + conditions and factors (the existence of pri- Ethambutol tbl. a 275 mg 1x4 and B complex or neuropsychiatric and internal symptoms, tbl. 3x1 – for next five months).

Alcoholism and Psychiatry Research 2017;53:147-154 Pupić-Bakrač, Radović, Pupić-Bakrač, Markota, Pupić-Bakrač 149

Table 1. Concentration of sodium, potassium, chloride, urea and creatinine during 8 days of hos- pitalization, and on control examination (23 days after admission); Na+ – sodium, K+ – potassium, Cl– – chloride.

Parameter Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Day 23 Na+ (mmol/L) 98 106 108 114 128 128 129 128 144 K+ (mmol/L) 3.2 3.9 4.3 4.1 3.5 3.8 4.0 4.1 5.3 Cl– (mmol/L) 64 72 73 79 96 94 91 94 103 Urea (mmol/L) 1.4 2.8 1.9 1.0 1.9 / 4.1 2.5 / Creatinine (µmol/L) 49 58 53 48 47 / 74 54 /

The following physical status was de- 0.9% NaCl sol. a 250 mL x 2; to which pa- scribed after the clinical examination: the tient was unresponsive in clinical status. An patient had an asthenic physique, he was emergency brain Multislice Computed To- conscious, disorientated in space and time, mography scans showed atrophy of cerebral verbally contactable, and with deficient parenchyma, and no acute pathomorphologi- thought content, in a mild psychomotor dis- cal changes. order, eupneic in rest. The eyes were normal- We got information from facility staff by ly positioned, pupils isochoric, with normal phone that patient spent a lot of time near reactions to light. The physical examination the water tap in the past few days (probably of the head and cranial nerves was without a drinking large amounts of water). Due to sus- pathological substrate. Meningeal signs were picion of possible hyponatremia, infusion of negative. In the upper and lower Mingazzini 0.9% NaCl sol. a 500 mL was included in the test there were no signs of lateralization. In therapy while waiting for laboratory findings. the standing position, patient was falling for- Reviewing the laboratory results of standard ward. Deep tendon reflexes were of appro- biochemistry, it was observed that sodium priate and symmetric response. Pathological concentration was 98 mmol / L. The urine reflexes were not present. The patient was in and ABG results were within the reference diapers, with urinary incontinence. values (urine specific gravity: 1010 kg/L). There were no pathological signs on the The patient was hospitalized to a Polyva- electrocardiogram and the vital parameters lent Intensive Care Unit and the correction were as follows: RR 165/100 mm Hg, heart of sodium concentration started by restric- rate 72 / min, hemoglobin oxygen satura- tion of water intake (maximum 2 L / day), in- tion (SpO2) 98%, blood sugar level (BSL) 7.2 fusions of hypertonic NaCl solution (7.5%) mmol / L, axillary temperature (Tax) 36.7 °C. and preoral salt intake. During the 8 days, After the examination, samples were tak- gradual titration of the mineral concentration en for laboratory analysis of blood (CBC (Table 1) was achieved and the initial diure- and standard biochemistry), urine and arte- sis of 15,000 mL was reduced to 3 500 mL rial blood gases (ABG). The following ther- (urinary output measured by indwelling cath- apy was ordered: Diasepam sol. a 10 mg + eter). During hospitalization, the patient was

Psychogenic Polydipsia & Water Intoxication Alcoholism and Psychiatry Research 2017;53:147-154 150 with normal vital parameters, hemodynami- they drink, was not because of the feel of cally stable, without repeated convulsive sei- but because they wanted to clean, wash zures. Consequently, he was examined by the or rinse worms for example, therefore pa- psychiatrist, who made the modification of tients usually gave delusional explanations neuropsychiatric therapy. Internist therapy [7]. Epidemiologic researches by authors was also adapted. Therapy at discharge was: from the US showed that 5% of chronic psy- Amlodipine tbl. a 10 mg 1x1, Metoprolol tbl. chiatric patients had at least once in a lifetime a 12.5 mg 2x1, Sodium valproate tbl. a 300 an episode of water intoxication. About 20% mg 1 + 0 + 2, Haloperidol tbl. a 2 mg 3x1, of all respondents had psychogenic polydip- Promazine tbl. a 25 mg 1 + 1 + 2, Diasepam sia, of which about 30% progressed to wa- tbl. a 5 mg 3x1, Biperiden hydrochloride tbl. ter intoxication. About 80% of respondents a 2 mg 1x1 and extension of antituberculous who had diagnosis of psychogenic polydipsia therapy. The ninth day after admission, the were from the “schizophrenic” group [8,9]. patient was released to the facility for adults At the Department of Emergency Medi- with special needs. The medical staff were cine, the major clinical challenge is to recog- given instructions on the control of peroral nize water intoxication from other emergency water intake and the need for periodic tests conditions and promptly administer adequate of serum . treatment. In extremely severe acute hypona- tremia the clinical picture rapidly progresses to coma and death outcome [3,10]. In pre- Discussion sented case, the patient was particularly com- The pathophysiology of psychogen- plicated because of a diagnosis of idiopathic ic polydipsia is still not completely under- epilepsy in medical history, with antiepileptic stood. The current researches suggest that therapy prescribed. Given the clinical picture it is a result of combined impact of several dominated by the seizures of the right ex- factors. The generally accepted explanation tremities, nausea and urinary incontinence, a is that patients with psychogenic polydipsia primary diagnosis of partial epileptic seizures have impairment of thirst center function, was established. Since the patient was resis- thus they have a much lower threshold for tant to the ordered therapy, we had doubts thirst than the general population. This re- about the possible secondary cause of sei- sults in polydipsia until the plasma osmolar- zures. Detailed heteroanamnesis and insight ity drops deeply below the physiological lev- into the laboratory results gave us a final an- el, even when antidiuretic hormone (ADH) swer on presence of dilution hyponatremia is fully suppressed. The probable cause for and water intoxication. this malfunction is the disturbed interaction This case is also interesting because of of neurotransmitters and hormones at the another fact, and that is an extremely low lymphic-hypothalamic-pituitary-adrenal axis sodium level of 98 mmol / L which is, ac- level. Apart from psychotic decompensation, cording to our findings, one of the lowest factors for exacerbation may be certain psy- measured concentrations in the serum of the chopharmaceuticals, decreased levels of po- living man. Previously, only few cases with a tassium and others [6]. Among patients, the sodium concentration of less than 100 mmol most common answer to the question why / L were reported in the literature [11,12,13].

Alcoholism and Psychiatry Research 2017;53:147-154 Pupić-Bakrač, Radović, Pupić-Bakrač, Markota, Pupić-Bakrač 151

However, in most cases hyponatremia was chronic intoxication. If based on anamnesis caused by a different mechanism, within the and clinical examination we cannot safely de- syndrome of inappropriate antidiuretic hor- termine the time of development of water mone secretion (SIADH) [12,13]. Among the intoxication, it is best to assume that it is a general population, the fatal outcome occurs chronic condition and treat it that way [12]. at considerably higher sodium concentra- Except psychogenic polydipsia, other pos- 10 tions, usually below 120 mmol / L . Possible sible factors associated with pathophysiology cause for tolerance of such an extreme hypo- of hyponatremia in the presented case could natremia in our case is chronic water intoxi- be the consumption of certain medications cation, i.e. development of intoxication over and . Our patient had Carbam- a period of more than 48 hours. Brain ad- azepine in his therapy, and it is proven that aptation to reduced serum osmolarity begins this antiepileptic is associated with drug-in- immediately after initial sodium level decline duced hyponatremia [17]. He was also treated and ends after 2-3 days [14]. It happens in a with several other medications that were re- way that brain cells lose soluble substances ported to have an effect on lowering serum with the consequent osmotic movement of sodium within SIADH – Sodium valproate water from the cells, thereby reducing brain [18], Haloperidol [19] and Lisinopril [20]. edema. Due to brain’s acclimatization to new Furthermore, antipsychotics he consumed homeostasis, symptomatology of chronic in- have dry mouth as a side effect, and conse- toxication is much more subtle than that of quent excessive water intake [6]. Mild hypo- an acute intoxication (development within kalemia, acknowledged from laboratory find- 48 hours) [15]. This is also evident from the ings, could arise as a result of malnutrition (as example of our patient, whose clinical pic- the patient was asthenic and with recurrence ture, given the severity of hyponatremia, was of tuberculosis), but also due to vomiting. much milder than expected. It is a trap that, Conclusively, the pathophysiology of hypo- in practice, can lead the clinician to underes- natremia was most likely multifactorial, with timate the condition of the patient and post- pone the correct diagnosis and application of the combined influence of all listed factors. treatment. Furthermore, chronic water intoxication Conclusion has its own specificity vis-à-vis acute in ther- Water intoxication is an emergency medi- apeutic terms. The recoupment of sodium cal condition that is, due to non-specific in the chronic form should be gradual and symptomatology and low incidence, initially carefully titrated, as rapid plasma osmolality often replaced with neurological and inter- increase causes brain cell drainage and conse- nal emergency conditions, especially if they quent demyelination. Osmotic demyelination are present in the medical history. In patients can lead to irreversible neurological deficits, with a psychiatric diagnosis (schizophrenia, seizures, coma, and in severe cases – death anorexia nervosa, personality disorders, au- [16]. Therefore, not only that the diagnosis tism, anxiety-depressive disorder, etc.), espe- of water intoxication should be differentiated cially those suffering from chronic psychosis, from other medical conditions, but it should that are developing acute neurological symp- also be differentiated whether it is acute or tomatology, it is always necessary to differen-

Psychogenic Polydipsia & Water Intoxication Alcoholism and Psychiatry Research 2017;53:147-154 152 tial-diagnostically think about possibility of Acknowledgements water intoxication. Water intoxication, even None with extremely severe hyponatremia, can be treated to the full extent of recovery, without residual neurological deficits. Conflict of interest None to declare

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Ozbiljna hiponatrijemija i intoksikacija vodom- Dijagnostički izazov u hitnoj medicini Sažetak - Psihogena polidipsija je poremećaj kompulzivnog pijenja vodc u psihijatrijskih pacijenata, najčešće onih koji boluju od kronične psihoze. Poremećaj može uzrokovati tešku hiponatrijemiju i intoksikaciju vodom, a manifestira se putem cerebralnog edema i popratnih neuroloških simptoma. 43-godišnji pacijent zaprim- ljen je na odjel hitne medicine zbog konvulzija desne ruke i noge koje su započele jedan sat prije dolaska. Za vrijeme trajanja napada pacijent je bio pri svijesti, jednom je povraćao i imao urinarnu inkontinenciju. Anam- neza je pokazala da pacijent boluje od epilepsije, kronične psihoze i umjerene mentalne retardacije. Vitalni parametri su bili stabilni i tijekom fizičkog pregleda nisu uočeni nikakvi popratni patološki znakovi. Uzeti su uzorci za laboratorijsku analizu i i putem infuzije je uključena terapija Diazepama (20mg) na koju je pacijent bio rezistentan. Iz heteroanamnestičkih podataka utvrđeno je da je pacijent posljednjih nekoliko dana proveo dosta vremena pijući vodu. Laboratorijski nalazi su pokazali da je koncentracija natrija 98 mmol/l. Postepeno smo počeli normalizirati razinu natrija nakon čega se pacijent u potpunosti oporavio. Intoksikacija vodom je hitno stanje koje se u kliničkoj praksi često zamijeni s drugim neurološkim i internističkim hitnim stanjima zbog svoje nespecifične simptomatologije. Pravovremenom dijagnozom i odgovarajućom terapijom oporavak je potpun. Ključne riječi: polidipsija, psihogen, hiponatrijemija, intoksikacija vodom

Psychogenic Polydipsia & Water Intoxication Alcoholism and Psychiatry Research 2017;53:147-154