OA Ogundipe1 and C Cross2
1Acting up Consultant, and 2Foundation Year 2 Doctor, Dept. of Medicine of the Elderly, Royal Victoria Hospital, 13 Craigleith Road, Edinburgh EH4 2DN, Scotland. Tel. (+44) 0131 537 5023 Fax. (+44) 0131 537 5140
Correspondence to Dr OA Ogundipe on email: ola_ayodele@hotmail.com
SMJ 2009 54(1): 58
Abstract
Keywords: Hyponatraemia, proton pump inhibitor, side-effect, reversible.
Case
Report
A 98-year-old Caucasian woman was admitted to hospital following a fall and resultant left neck of femur fracture. Her medical history revealed angina, hypertension, type 2 diabetes and hypothyroidism. Medications were aspirin 75mg daily, omeprazole 10mg daily, nicorandil 10mg twice daily, isosorbide mononitrate MR 60 mg daily, simvastatin 40mg daily, bisoprolol 5mg daily, levothyroxine 75 micrograms daily, glipizide 5mg twice daily and one Adcal-D3 tablet twice daily.
She was noted to have chronically low serum sodium concentration that was usually between 125 and 130 mmol/L (normal 135 – 145). She appeared to have been asymptomatic and was clinically euvolaemic. Abbreviated mental test score was 9/10. The hip fracture was repaired uneventfully with cannulated screws under spinal anaesthesia.
A few days post-operatively, she developed a symptomatic Escherichia coli urinary tract infection that responded well to oral trimethoprim based on sensitivities. She subsequently developed new symptoms (headaches, lethargy and gait imbalance) that persisted for a further two weeks. There was no lateralising neurology; repeat midstream urine showed no bacteriuria and serum sodium levels remained in the aforementioned range.
Further evaluation demonstrated normal blood count, potassium, renal and liver function, calcium, magnesium, c-reactive peptide, protein electrophoresis, triglycerides, cortisol and chest X-ray. Thyroid function tests suggested adequate supplementation. Pre-meal capillary glucose monitoring ranged between 4 and 9mmol/L, with an HbA1c of 7.8%. Serum osmolality was 275mosm/Kg (normal 280-296), urine sodium 55 mmol/L, urine osmolality 334mosm/Kg, and urine Bence-Jones protein negative.
With hindsight, serum sodium levels were normal prior to introduction of the proton pump inhibitor (PPI) omeprazole six months earlier at her local surgery for mild reflux symptoms. The hyponatraemia appeared to have developed progressively thereafter. As no clear cause had been identified at that stage, and as she had remained asymptomatic, she was monitored without treatment.
Based
on the temporal relationship, and as the reflux symptoms had resolved, the
omeprazole was withdrawn. Serum sodium level normalised to 138mmol/L within
seven days with resolution of the headache, lethargy and gait imbalance. Over
the subsequent three weeks, checks revealed no recurrence of hyponatraemia.
She progressed with rehabilitation and was discharged home soon thereafter, independently mobile with a wheeled frame, able to climb a flight of stairs with two rails, continent, and with a daily visit to supervise personal care.
Discussion
Rare cases of reversible hyponatraemia associated with the use of PPIs have been reported in the medical literature.1 - 4 The mechanism is not fully established but excessive urinary sodium loss has been postulated due to PPI effects on renal tubular ion exchange. An alternative hypothesis is fluid retention possibly related to a syndrome of inappropriate antidiuretic hormone (SIADH) secretion or action.
The side-effect might not simply be a PPI class-effect. A case of acute onset and reversible hyponatraemia associated with esomeprazole has been reported in a patient who had previously taken lansoprazole for three years without complication.4
Previously
reported cases in the literature appear to have developed symptoms shortly after
initiation of PPI therapy. The case presented here is notable as it adds the
caution that symptoms may be minimal initially, thus making it easier to
overlook the rare association.
Age-related changes to osmoregulation are thought to occur in older patients, and certain medications might aggravate a tendency to hyponatraemia.5 In this case, it is also possible that stressful triggers like surgery or infection may have precipitated the acute onset of symptoms, given the previous state of asymptomatic chronic hyponatraemia.
It
has been argued that PPIs are overprescribed; a problem occurring both in
primary and secondary care. It is further noted that there is suboptimal review
of the need to continue regular use of these medications.6 Given the
impact that symptomatic hyponatraemia can have on the health, functional
abilities and independence of older patients, it is important for clinicians to
be aware of this possible side-effect to PPIs, and to consider it in the
differential diagnoses.
Key points
·
Hyponatraemia is a rare side-effect associated with PPI therapy.
·
Its presentation may be variable, being either symptomatic soon
after initiation of treatment, or being minimally symptomatic initially and thus
potentially easier to overlook.
·
The hyponatraemia may be reversible upon cessation of use of PPIs.
References
1. Durst RY, Pipek R, Levy Y. Hyponatremia caused by omeprazole treatment. Am J Med 1994;97:400-1.
2. Shiba S, Sugiura K, Ebata A et al. Hyponatremia with consciousness disturbance caused by omeprazole administration. A case report and literature review. Dig Dis Sci 1996;41:1615-7.
3.
Fort E, Laurin C, Baroudi A, Liebaert-Bories MP, Strock P. Lansoprazole-induced
hyponatremia. Gastroenterol
Clin Biol 2000 Jun-Jul; 24(6-7):686.
4.
Mennecier D, Ceppa F, Gidenne S, Vergeau B. Hyponatremia with
consciousness disturbance associated with esomeprazole. Ann Pharmacother. 2005
Apr;39(4):774-5.
5.
Miller M. Hyponatremia: age-related risk factors and therapy decisions.
Geriatrics 1998;53:32-48.
6. Forgacs I, Loganayagam A. Overprescribing of proton pump inhibitors is expensive and not evidence based. BMJ 2008;336:2-3.