Hyponatremia bea rs

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  • Hyponatremia bea rs

    1. 1. Thiazide Induced Hyponatremia in the Elderly Toma Timothy BSc MD.
    2. 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. 3. Hyponatremia • Low Serum Sodium: Na<128 -130 mmol/L • Behavior change, seizure, somnolence, vomiting, asymptomatic. • Central pontine demyelination--->death.
    4. 4. Question • What are the RISK FACTORS for thiazide induced hyponatremia in the elderly?
    5. 5. Literature Search • EBSCO Host: • Search Terms: Thiazides, Hyponatremia, Elderly, risk factors. • Limits: English Language, humans, full text articles • Results: 6 articles
    6. 6. Evaluation Method • JAMA work sheets (HARM) • Relevancy to Patient • Articles excluded: unrelated to thiazides (2), unrelated to patient (1)
    7. 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. 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. 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. 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. 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. 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. 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. 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. 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. 16. Conclusion • Caution warranted when prescribing thiazides to elderly patients with a low body mass and low serum K.
    17. 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. 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. 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. 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. 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. 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. 23. Risk Factors Are • Increasing Age • Low Body Mass • Low Serum Potassium • Female Gender
    24. 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. 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
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