1. Thiazide Induced
Hyponatremia in the
Elderly
Toma Timothy BSc MD.

2. Patient
• Mrs H. 73 year-old First Nations lady.
• Initially had a hypoglycemic episode at home (BG 1.0mmol), then 1 week of
altered behaviour and a chief complaint of feeling “sick.”
• PMhx: Diabetes (A1c 7.0), HTN, hyperlipidemia, asthma, binge drinking, UTI.
• Meds: HCTZ 25mg (since 2006), Metformin 500mg BID, Glicazide 80mg,
ASA 81mg, Diovan 80mg, vit C&D, and Etidrocal Kit.
• Labs
• Na 128 mmol/L (133-146mmol)
• Potassium 5 mmol/L (3.5- 5.0 mmol)
• CT Head: Age related atrophy, mild ischemic changes.
• Withdrew HCTZ, Na normalized.

3. Hyponatremia
• Low Serum Sodium: Na<128 -130 mmol/L
• Behavior change, seizure, somnolence,
vomiting, asymptomatic.
• Central pontine demyelination--->death.

4. Question
• What are the RISK FACTORS for thiazide
induced hyponatremia in the elderly?

5. Literature Search
• EBSCO Host:
• Search Terms: Thiazides, Hyponatremia,
Elderly, risk factors.
• Limits: English Language, humans, full text
articles
• Results: 6 articles

6. Evaluation Method
• JAMA work sheets (HARM)
• Relevancy to Patient
• Articles excluded: unrelated to thiazides (2),
unrelated to patient (1)

7. • ARE THE RESULTS VALID?
Cohort Studies: Aside from the exposure of interest, did the exposed and control groups start and finish with the same risk for the outcome?
• Were patients similar for prognostic factors known to be associated with the outcome (or was statistical adjustment done)?
• Were the circumstances and methods for detecting the outcome similar?
• Was the follow-up sufficiently complete?
Case-Control Studies: Did the cases and control group have the same risk (chance) for being exposed in the past?
• Were cases and controls similar with respect to the indication or circumstances that would lead to exposure?
• Were the circumstances and methods for determining exposure similar for cases and controls?
WHAT ARE THE RESULTS?
How strong is the association between exposure and outcome?
• What is the risk ratio or odds ratio?
• Is there a dose-response relationship between exposure and outcome?
How precise was the estimate of the risk?
• What is the confidence interval for the relative risk or odds ratio?
HOW CAN I APPLY THE RESULTS TO PATIENT CARE?
Were the study subjects similar to your patients or population?
• Is your patient so different from those included in the study that the results may not apply?
Was the follow-up sufficiently long?
• Were study participants followed-up long enough for important harmful effects to be detected?
Is the exposure similar to what might occur in your patient?
• Are there important differences in exposures (dose, duration, etc) for your patients?
What is the magnitude of the risk?
• What level of baseline risk for the harm is amplified by the exposure studied?
Are there any benefits known to be associated with the exposure?
• What is the balance between benefits and harms for patients like yours?

8. Article 1: Thiazide Diuretic Prescription and Electrolyte
Abnormalities in Primary Care
Clayton, J. A.; Rodgers, S.; Blakey, J.; Avery, A.; Hall, I. P.. British Journal of Clinical Pharmacology, Jan2006, Vol. 61 Issue 1, p87-95,
• A cross-sectional observational study
• Retrospective computerized search (MIQUEST system) of patients aged ≥18
years in 12 Primary Care practices in the UK (32,218)
• Date, Dose and Name of any thiazide prescribed within the given time frame and the
date and results of electrolyte tests were searched for.
• Detailed prescribing data were obtained for 2942 patients: median age 68 years (range
19–99).

9. Article 1: Thiazide Diuretic Prescription and Electrolyte
Abnormalities in Primary Care
Clayton, J. A.; Rodgers, S.; Blakey, J.; Avery, A.; Hall, I. P.. British Journal of Clinical Pharmacology, Jan2006, Vol. 61 Issue 1, p87-95,
• 951 out of 2942 (32.3%) had a recorded check of their electrolytes.
• 196 (20.6%) had a sodium and/or potassium concentration below the normal
range.
• 130 (13.7%) patients were within the hyponatremic range
• Odds ratio for developing hyponatraemia in patients over 70 years was 3.87
compared with those of≤70 years.
• Findings suggest that when prescribing a thiazide,especially in the elderly, regular
checks of sodium concentration should be performed.
• Risk Factor: elderly >70 years

10. Article 1: Thiazide Diuretic Prescription and Electrolyte
Abnormalities in Primary Care
Clayton, J. A.; Rodgers, S.; Blakey, J.; Avery, A.; Hall, I. P.. British Journal of Clinical Pharmacology, Jan2006, Vol. 61 Issue 1, p87-95,
• A dose-dependent effect for hyponatremia was not seen
• Thiazides implicated:
• bendroflumethazide 2.5mg (n=2615) to 5mg (n=273)
• indapimide
• “other HCTZ”
• metalozone
• The hyponatremia was identified on the first electrolyte check in the majority
of patients but in 20% it was detected on subsequent samples.

11. How Can I Apply these Results to My
Patient?
• No dose dependence.
• Thiazides Implicated: bendroflumethazide 2.5-5mg,
indapimide, metalozone, “other thiazides”
• Are all thiazides the same?

12. Article 2: Risk Factors for Thiazide Induced Hyponatremia
Chow et al., Q J Med 2003; 96:911-917
• Retrospective Case Control Trial
• Cases drawn from symptomatic hyponatremia
(Na<130 mmol) requiring hospital admission from
1996-2002 in Hong Kong.
• Controls taken from 8420 patients taking thiazides at the
same institution.

13. Article 2: Risk Factors for Thiazide Induced Hyponatremia
Chow et al., Q J Med 2003; 96:911-917
• Indapamide (42.8%)
• HCTZ + amiloride (17.3%)
• HCTZ only (16.1%)
• HCTZ + traimterene (15.4%)
• bendrofluazide (8.4%)
• Doses not given

14. Article 2: Risk Factors for Thiazide Induced Hyponatremia
Chow et al., Q J Med 2003; 96:911-917
• Risk Factors Identified (univariate analysis):
• serum K level
• indapimide use
• elderly home institution
• physical immobility
• NOT Risk Factors: gender , duration
(more females prescribed thiazides)
of thiazide use, loop diuretics, ACE I,NSAID use,
and kidney function.

15. Article 2: Risk Factors for Thiazide Induced Hyponatremia
Chow et al., Q J Med 2003; 96:911-917
• Independent Risk Factors (multi-variate analysis by logistic regression analysis)
• Body Weight
• 5 kg increase in mass = 27% decrease in hyponatremia
(Odds ratio; 0.77, 95% CI 0.68-0.87 p<0.0001)
• Serum Potassium
• One SD increase (8.4mmol) = 63% decrease in risk.
(Odds ratio 0.37, 95% CI 0.27-0.50 p<0.0001)
• Age
• Each 10 year increment of age was associated with a two-fold increase in risk
(Hazards ratio 2.14, 95% CI 1.59-2.88)

16. Conclusion
• Caution warranted when prescribing
thiazides to elderly patients with a low
body mass and low serum K.

17. How Can I Apply these Results to My
Patient?
• Case Group of patients were hospitalized with
symptomatic hyponatremia.
• What other comorbidities were there in patients
in this study?
• Thiazide use a red herring? ie. SIADH?
• Study was in China, body mass differences with
North Americans?

18. Article 3: Diuretic Induced Hyponatremia in Elderly
Hypertensive Women
Sharabi Y et al., JHH (2002) 16, 631-635
• Chart Review of all patients hospitalized from
1990-1997 with hyponatremia Na<135mmol
• Patients with other possible causes for
hyponatremia were excuded (CHF, cirrhosis, hypothyroid, nephrotic
syndrome, uncontrolled DM).
• Only patients receiving diuretic therapy with no
other possible explanations for their hyponatremia
were included in the analysis.

19. Article 3: Duiretic Induced Hyponatremia in elderly hypertensive women
Sharabi Y et al., JHH (2002) 16, 631-635
• 5384 patients with hyponatremia
• 180 patients with diuretic induced
hyponatremia
• Most received Hydrochlorothiazide
• Daily Dose: 35 +/- 18 mg

20. Article 3: Duiretic Induced Hyponatremia in elderly hypertensive women
Sharabi Y et al., JHH (2002) 16, 631-635
• Results
• Hyponatremia:
• in women vs men OD 3.10 (95% CI 2.07-4.67)
• Older than 75 vs Younger than 75 OD 6.62 (95%CI 4.82-9.10)
• Older than 65 vs Younger than 65 OD 9.87 (95%CI 5.93-16.64)
• Older than 75 vs Younger than 65 OD 16.64 (95%CI 9.84-28.47)
• 37% of cases were on a thiazide for greater than a
year.

21. Article 3: Duiretic Induced Hyponatremia in elderly hypertensive women
Sharabi Y et al., JHH (2002) 16, 631-635
• Conclusion: Diuretic induced hyponatremia
may be insidious, and appears mainly in
elderly women.

22. How Can I Apply these Results to My
Patient?
• Falls near the age range for highest risk of
thiazide induced hyponatremia, age 73.
• Cases have similar
comorbidities( Diabetes, HTN) to Mrs H.
• Hydrochlorothiazide use

23. Risk Factors Are
• Increasing Age
• Low Body Mass
• Low Serum Potassium
• Female Gender

24. Recommendations
• Elderly patients, especially women age 75 and over
are at greater risk of thiazide induced
hyponatremia.
• Check Na, K levels regularly in the elderly,
especially frail elderly on a thiazide diuretic.
• No dose dependent effect but........ star low, go
slow.

25. References
• Clayton, J. A.et al. Thiazide Diuretic Prescription and Electrolyte
Abnormalities in Primary Care British Journal of Clinical Pharmacology,
Jan2006, Vol. 61 Issue 1, p87-95
• Chow et al., Risk Factors for Thiazide Induced Hyponatremia
Q J Med 2003; 96:911-917
• Sharabi Y et al., Duiretic Induced Hyponatremia in Elderly Hypertensive Women.
JHH (2002) 16, 631-635