Persistent hiccups in cancer patient: a presentation of syndrome of inappropriate antidiuretic hormone induced hyponatremia.

Hyponatremia is quite common in cancer patients, but the presentation as persistent hiccups is not common. Literature over hiccups development due to hyponatremia is quite scant. Hiccups are of various types, persistent hiccups are those that last more than 48 h and remains less than 1 month. Hiccups lasting more than 24 h require investigation for an underlying organic etiology, with hyponatremia included in the differential diagnosis. This paper discusses a carcinoma lip patient presented with the persistent hiccups and unconsciousness post-operatively. The patient was initially responded with trials of both metoclopramide and Ryle's tube insertion, but eventually, his hiccups resolved only after treatment of hyponatremia. Patient's clinical course and investigations suggest an etiology of syndrome of inappropriate antidiuretic hormone (SIADH) secretion behind the hyponatremia. Study suggested that SIADH linked hyponatremia should be considered in the differential diagnosis of cancer patients with refractory hiccups.

INTRODUCTION

A hiccup is a single or series of involuntary spasm of the diaphragm and intercostals muscle of variable spacing and duration, followed by the sudden closure of the glottis.[1] Hiccups can arise due to sudden over distension of stomach such as after overeating, rapid eating, laughing, sudden temperature changes or due to various infections, central nervous system disorders, after use of certain drugs, nerve damage or irritation and in multiple metabolic or electrolyte disturbances.[23] It may cause the victim under significant distress and may be refractory to most of the treatments. Hiccups are of various types (acute, persistent, intractable, and recurrent) in which persistent hiccups are those that lasts more than 48 h and remain less than 1 month.[4] Hiccups persist more than 24 h require investigation to find out an underlying organic etiology. Here, we report a case that developed persistent hiccups due to severe hyponatremia, which was caused by the syndrome of inappropriate anti diuretic hormone (SIADH) secretion. The possible causes of hyponatremia and SIADH with points which correlate hyponatremia due to SIADH discussed further.

CASE REPORT

A 70-year-male with carcinoma lower lip underwent radical excision of the lower lip with cheek advancement with karpandzic flap uneventfully under general anesthesia. The significant medical history included chronic obstructive pulmonary disease (COPD), which was optimized on salbutamol puffs. On post-operative day eleventh, patient developed hiccups, which responded to intravenous metoclopramide thrice a day and Ryle's tube insertion. After 2 days, patient developed persistent hiccups followed by the altered sensorium. He was shifted to intensive care unit. His pulse rate was = 125/min, B.P = 150/100, Chest = B/L coarse crepts, R.R = 30/min, SpO2= 90-91%. Hudson mask was put with 6 L. Oxygen flow, patient nebulized and extensive chest physiotherapy given, thick secretions removed through suction and this improved air entry, respiratory rate improved to 22 and SpO2, became 93-94%. Emergency investigations sent that showed Hb = 13.2 gm/dL, Platelet count = 2.2 lac/mm3, Total leucocyte count (TLC) = 25 thousand/ mm3, S. urea = 17 mg/dL, S. creat = 0.6 mg/dL, S. uric acid = 3 mg/dL, S. sodium = 107 meq/L, S. potassium = 3.8 meq/L, S. bilurubin = 0.6 mg/dL, S. albumin = 2.3. Chest X-ray showed a small patch in right lower zone. Central line was placed, Central venous pressure (CVP) = 6-8 mmHg.

Patient hyponatremia was treated with 3% sodium chloride (NACL) given @ 30 mL/h, and to find out the cause, Urine osmolality and U. sodium sent for investigation which was 302 and 197 meq/L respectively.

Since, patient was euvolemic (CVP = 6-8 mmHg) and after considering other reports, the cause of hyponatremia was thought to be SIADH. The points, which correlate the finding with cause are:

The cause of SIADH could be post-surgical stress, present in this patient

The patient was a case of COPD with superimposed infections, again a cause of SIADH

Patient was euvolemic (CVP bet. 6-9)

BUN, S. creatinine, S. uric acid, S. albumin in normal to subnormal range. Acid base, serum k+ and other electrolytes were in the normal range

U. sod. >20 meq/L and U. osmolality >300 mosm.

Keeping the diagnosis of SIADH induced hyponatremia, patient treated with 3% NACL, fluid restricted to 1000-1200 mL/Day and antibiotics were step up for the chest point of view. With the help of extensive chest physiotherapy, nebulization, and broad spectrum antibiotics chest was improved, TLC reduced day by day and reached to 8000/mm3. When S. sodium reached to 119 meq/L, patient became oriented, obeyed commands. After 44 h patient's serum sodium reached to 130 meq, then hypertonic saline was stopped and intravenous 0.9% saline started @ 1200 mL/24 h. As the patient was fully conscious and oriented, his feed started through Ryle's tube and in day 3, patient's oral feed started, which was rich in sodium and then patient was shifted back to ward in stable condition.

DISCUSSION

Hiccups may be considered benign, but sometimes, they indicate some serious metabolic disorder and may be the earliest presenting feature. In oncology patient undergoing major surgery, this could be of significance as it could lead to increase morbidity. It has been reported that chances of hiccups increases17 folds with every decrease in 10 meq/L of serum sodium.[5] Very few cases have been reported so far that revealed manifestation of hiccup as a cause of hyponatremia. Jones et al.[6] Has been reported two cases that correlate hiccups with the hyponatremia. According to Lazarevic et al.[7] Hiccups could be a sign of severe hyponatremia so always should be kept in the differential diagnosis. For the correct and effective management of hyponatremia cause should be find out. Extracellular volume (ECV) plays a major role for detecting the cause of hyponatremia. According to ECV hyponatremia can be divided in 3 types.[8]

Hypovolemic hyponatremia-both water and sodium loss present (due to diarrhea, vomiting, diuretic etc.,) but hyponatremia develops due to replacement of lost fluid by hypotonic fluid. Site of loss is renal (urine Na+ >20 meq/L) or extrarenal (urine Na+ <10 meq/L)

Isovolemic hyponatremia-water gain exceeds than the capacity to excrete. Like in SIADH (urine Na+ >20 meq/L and urine osmolality >100 mosm/kgh20) and acute water intoxication (urine Na+ <10 meq/L and urine osmolality <100 mosm/kgh20)

Hypervolemic hyponatremia-both sodium and water increases, with the water gain exceeding the sodium gain. Causes are heart failure, hepatic failure (Urine Na+ <20 meq/L), renal failure (Urine Na+ >20 meq/L).

In our case, the likely cause of hyponatermia could be SIADH which may be seen after a major oncology surgery.[2] The SIADH[9] is a condition mostly found in patients diagnosed with small-cell carcinoma of the lung, pneumonia, brain tumors, head trauma, strokes, meningitis, and encephalitis, also found in patient of COPD, pneumonia, pneumonitis, tuberculosis and post-surgical stress. This syndrome is characterized by excessive release of antidiuretic hormone (ADH or vasopressin) from the posterior pituitary gland or another source, the result is hyponatremia, and sometimes fluid overload.

The management of hyponatremia must be done according to the underlying cause and volume status. In SIADH induced hyponatremia treatment is – fluid restriction, hypertonic saline administration and abolition of stimuli causes ADH hypersecretion. Both hyponatremia and its treatment can lead to serious neurological complication. Cerebral edema usually occurs in acute hyponatraemia of moderate or severe degree (drop in serum sodium ≤125 mmol/L in ≤48 h). It is a medical emergency that, if left untreated, can lead to herniation of the brain stem into the foramen magnum and permanent brain damage.[10] Hyponatremia must be corrected slowly because rapid correction can lead to the development of central pontine myelinolysis (cpm), a severe neurological disease. During treatment of hyponatremia, the serum sodium should not be allowed to rise by more than 8 mmol/L over 24 h (i.e., 0.33 mmol/L/h rate of rise).

Based on a retrospective analysis of 64 patients, Sterns[11] found that neurologic complications tend to occur if the rate of correction exceeds 0.6 mmol/L/h. 62 out of the 64 patients who were treated, 5 died (for mortality of 8%), because the rate of correction of the serum sodium concentration exceeding 0.55 mmol/L/h. Another retrospective study conducted by Tanneau et al.[12] over a 10 years period on 12 polydipsic patients revealed that patients with neurologic complications had a higher maximal 24-h increase in plasma sodium concentration (21.8 ± 3.9 vs. 15.5 ± 5.1 mmol/L, P < 0.02), and a higher incidence of overcorrection to hypernatremia.

CONCLUSION

It is concluded that in patient with a chest infection and after major oncology surgery, hiccups may be the earliest sign of electrolyte disorder (hyponatremia). Hyponatremia should be considered in the differential diagnosis of patients with the persistent hiccups. Early diagnosis, slow and judicious correction can reverse the condition otherwise irreversible brain injury may complicate the persisting condition.