What are the considerations for using Terbutaline (beta-2 adrenergic agonist) in a patient with End-Stage Renal Disease (ESRD)?

Terbutaline Use in End-Stage Renal Disease

Terbutaline can be used safely in patients with ESRD without dose adjustment, as severe renal impairment does not significantly reduce total drug clearance despite the drug's predominantly renal excretion in healthy individuals. 1

Pharmacokinetic Considerations in ESRD

• Total clearance of terbutaline remains relatively preserved in severe renal impairment (1.72 mL/min/kg in ESRD vs. 2.23-3 mL/min/kg in normal renal function), representing only a 23-43% reduction despite GFR <30 mL/min 1

• Renal clearance accounts for only approximately 15% (0.25 mL/min/kg) of total clearance in ESRD patients, indicating substantial non-renal elimination pathways compensate for lost kidney function 1

• The terminal half-life is prolonged to 7.93 hours (SD: 4.06) in ESRD compared to normal renal function, but this does not necessitate routine dose reduction 1

• Distribution volume at steady state is 0.74 L/kg with a mean residence time of 8.35 hours in ESRD patients 1

Dosing Recommendations

Standard dosing can be used in ESRD patients without routine adjustment, as the FDA label does not specify renal dose modifications and pharmacokinetic data demonstrate adequate total clearance through non-renal pathways 2, 1

• Monitor for signs of drug accumulation if using repeated doses, particularly watching for excessive beta-adrenergic stimulation (tachycardia >200 bpm, tremor, hypokalemia) 2

• Consider that dialysis does not significantly remove terbutaline, so timing relative to hemodialysis sessions is not critical 1

Cardiovascular Precautions in ESRD

Exercise heightened caution with terbutaline in ESRD patients due to their elevated baseline cardiovascular risk, as these patients demonstrate greater all-cause mortality and cardiovascular event rates 3

• Significant changes in systolic and diastolic blood pressure can occur with any beta-adrenergic bronchodilator and may be poorly tolerated in ESRD patients with pre-existing cardiovascular disease 2

• Monitor ECG changes including T-wave flattening, QTc prolongation, and ST segment depression, which have unknown clinical significance but warrant attention in this high-risk population 2

• Avoid use in patients with systolic blood pressure <80 mmHg or signs of peripheral hypoperfusion, as neurohormonal antagonism is poorly tolerated in advanced disease states 4

Drug Interaction Considerations

Be particularly vigilant about hypokalemia when terbutaline is combined with non-potassium-sparing diuretics, which are commonly prescribed in ESRD patients for volume management 2

• Beta-agonists produce hypokalemia through intracellular potassium shunting, and this effect is acutely worsened by loop or thiazide diuretics, especially when recommended doses are exceeded 2

• The clinical significance of combined hypokalemia is heightened in ESRD patients who already have electrolyte abnormalities and increased risk of cardiac arrhythmias 3

• Avoid concomitant use with other sympathomimetic agents, as the combined cardiovascular effects may be deleterious 2

• If the patient is on MAO inhibitors or tricyclic antidepressants (or within 2 weeks of discontinuation), administer terbutaline with extreme caution due to potentiated vascular effects 2

Monitoring Parameters

Monitor pulse rate, blood pressure, and symptoms of excessive beta-adrenergic stimulation at each administration, as ESRD patients may experience atypical presentations of complications 3

• Check serum potassium levels regularly, particularly when combining with diuretics 2

• Assess for signs of deteriorating asthma control, as increased terbutaline requirements may indicate need for anti-inflammatory therapy (corticosteroids) rather than escalating bronchodilator doses 2

• Watch for rare but serious adverse effects including seizures, which have been reported with terbutaline and did not recur after discontinuation 2

Common Pitfalls to Avoid

Do not assume terbutaline requires dose reduction simply because it is renally excreted in healthy individuals—the compensatory non-renal clearance pathways maintain adequate drug elimination in ESRD 1

• Avoid combining with beta-blockers, which can produce severe bronchospasm in asthmatic patients and block terbutaline's therapeutic effects 2

• Do not overlook the increased risk of adverse drug reactions in ESRD patients, who have a positive trend between number of medications, adverse drug reactions, and drug-drug interactions 5

• Recognize that ESRD patients may present with infections and other complications in atypical fashion, requiring focused history and physical examination 3

• Be aware that cardiovascular complications including pericarditis, acute coronary syndrome, and sudden cardiac death are more common in ESRD patients receiving any sympathomimetic agent 3