Friday, December 6, 2013

Terbutaline and Albuterol for Lowering of Plasma Postassium

The below abstracts show that beta 2 adrenergic agonists are effective at treating hyperkalemia.  They do so by "shifting" K into the cells. 
--0.5 mg of IV albuterol reduces K by about 1.2 mEq/L. 
-- A 20 mg neb (most are 2.5 mg) lowers it by about 1.0 mEq/L.  
--A 10 mg neb lowers it by about 0.6 mEq/L.
I give 0.25 mg of IM terbutaline to an adult, but only if it is critical, and add nebulized albuterol also.  I've never given it IV, as I'm a bit reluctant to risk the cardiac irritability.
1
TI
Treatment of hyperkalaemia in renal failure: salbutamol v. insulin.
AU
Lens XM, Montoliu J, Cases A, Campistol JM, Revert L
SO
Nephrol Dial Transplant. 1989;4(3):228.
Three groups of patients with acute or chronic renal failure (GFR less than 5 ml/min) and hyperkalaemia (K+ greater than or equal to 6 mEq/l), similar in age, serum creatinine and pretreatment K+. Group A (n = 24) received salbutamol 0.5 mg i.v. in 15 min, group B (n = 10) received glucose 40 g i.v. plus 10 units insulin i.v. in 15 min, and group C (n = 10) received salbutamol 0.5 mg i.v., glucose 40 g i.v. and insulin 10 units i.v. over a 15-min period. Serum potassium was measured at 30, 60, 180 and 360 min after administration of treatment. All treatments reduced serum potassium, maximal at 30 or 60 min, and ranging from -0.5 +/- 0.1 to -1.5 +/- 0.2 mEq/l; patients in group C exhibited a significantly greater decrement in serum potassium, when compared to group B at 60 (-1.5 +/- 0.2 vs -1 +/- 0.1 mEq/l, respectively; P less than 0.01) and 180 min (-1.2 +/- 0.2 vs -0.7 +/- 0.1 mEq/l, respectively; P less than 0.05). There were no significant differences between groups A and C. Patients from group C had moderate tachycardia and more prolonged hyperglycaemia than those from group B, but all treatments were well tolerated.
AD
Nephrology Service, Hospital Clínic, University of Barcelona, Catalonia, Spain.
PMID
2
TI
The management of hyperkalaemia in the emergency department.
AU
Ahee P, Crowe AV
SO
J Accid Emerg Med. 2000;17(3):188.
Life threatening hyperkalaemia (>7.0 mmol/l) is commonly associated with acute renal failure. Moderate hyperkalaemia (6.1-6.9 mmol/l) is also common and well tolerated in patients with chronic renal failure. Renal failure is the most common cause of hyperkalaemia although other causes to consider include drugs (potassium sparing diuretics, angiotensin converting enzyme inhibitors), hyperglycaemia, rhabdomyolysis and adrenal insufficiency. Hyperkalaemia affects the cardiac conducting tissue and can cause serious arrhythmias including ventricular fibrillation and asystolic arrest. Therefore it is important to treat hyperkalaemia promptly in the emergency department. This paper evaluates the therapeutic options available for treatment of hyperkalaemia.
AD
Department of Accident and Emergency Medicine, City Hospital, Birmingham.
PMID
3
TI
Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients.
AU
Allon M, Copkney C
SO
Kidney Int. 1990;38(5):869.
We evaluated in maintenance hemodialysis patients the potassium lowering effects of intravenous insulin with glucose, nebulized albuterol, and a regimen combining both modalities. There was a similar decrease in plasma potassium following either insulin with glucose (0.65 +/- 0.09 mmol/liter) or albuterol (0.66 +/- 0.12 mmol/liter), and a substantially greater fall with the combined regimen (1.21 +/- 0.19 mmol/liter, P less than 0.02 vs. either drug alone). Baseline plasma glucose concentrations were similar (about 4.8 mmol/liter) prior to all three treatments. Following insulin with glucose, plasma glucose increased transiently. but then fell to 2.8 +/- 0.3 mmol/liter at one hour, with concentrations below 3 mmol/liter in 9 of 12 patients. None of the patients had symptoms of hypoglycemia. Plasma glucose increased to 6.8 +/- 0.5 mmol/liter with albuterol. After the combined drug regimen plasma glucose rose transiently and was back to baseline (4.7 +/- 0.7 mmol/liter) at one hour. Treatment with insulin or albuterol produced trivial increases in heart rate, whereas the combined drug regimen was associated with a significant rise (15.1 +/- 6.0 min-1). These observations suggest that albuterol and insulin with glucose are equally efficacious in lowering plasma potassium in uremic patients, and that the hypokalemic effects of the two drugs is additive. The hypoglycemic effect of insulin is attenuated by coadministration albuterol. Combined therapy with insulin, glucose and albuterol isefficacious and safe for the acute treatment of hyperkalemia in hemodialysis patients.
AD
University of Oklahoma Health Sciences Center, Oklahoma City.
PMID
4
TI
Hyperkalemia in end-stage renal disease: mechanisms and management.
AU
Allon M
SO
J Am Soc Nephrol. 1995;6(4):1134.
Clinical investigations in the past few years have enhanced the understanding of the mechanisms of hyperkalemia in patients with ESRD. The results of these studies have led to modifications in the acute treatment and prevention of hyperkalemia in this patient population. They have confirmed the efficacy of intravenous insulin, while raising doubts about the utility of intravenous bicarbonate, for the acute treatment of hyperkalemia. Moreover, the beta-adrenergic agonist albuterol has been shown to be a useful adjunct to insulin for acutely lowering plasma potassium. Finally, there has been enhanced recognition of nondietary factors that can predispose to hyperkalemia in patients with ESRD, including prolonged fasting and the use of nonselective beta-adrenergic blockers. These new insights may improve the clinical management of hyperkalemia in patients with renal failure.
AD
PMID

5
TI
Effect of various therapeutic approaches on plasma potassium and major regulating factors in terminal renal failure.
AU
Blumberg A, Weidmann P, Shaw S, Gnädinger M
SO
Am J Med. 1988;85(4):507.
PURPOSE: The development of life-threatening hyperkalemia poses a risk for patients with chronic preterminal renal failure. Various therapeutic options have been suggested for hyperkalemic emergencies in these patients; to date, however, no study has evaluated the relative efficacies of these measures in the presence of renal failure. Our goal was to examine the acute effects of a variety of therapeutic approaches, as well as those of hemodialysis, on plasma potassium levels in a hemodialysis population.
PATIENTS AND METHODS: Ten patients with terminal renal failure undergoing maintenance hemodialysis were enrolled in the study. Blood gas parameters and plasma sodium, potassium, glucose, osmolality, renin, aldosterone, epinephrine, norepinephrine, dopamine, and insulin were measured before, during, and after 60-minute infusions of bicarbonate, epinephrine, and insulin in glucose, and before, during, and after performance of regular hemodialysis for one hour.
RESULTS: Hypertonic as well as isotonic intravenous bicarbonate (2 to 4 mmol/minute) induced a marked rise in plasma bicarbonate and pH, but failed to lower the plasma potassium level (5.66 versus5.83 mmol/liter before and after). Epinephrine, 0.05 microgram/kg/minute administered intravenously, decreased plasma potassium only slightly from 5.57 to 5.25 mmol/liter, and five patients showed no decline. On the other hand, insulin in glucose, 5 mU/kg/minute intravenously, effectively lowered plasma potassium levels from 5.62 to 4.70 mmol/liter, and hemodialysis induced the most rapid decline from 5.63 to 4.29 mmol/liter. Plasma aldosterone was elevated before treatment; it correlated with plasma potassium and dropped during intravenous bicarbonate administration or hemodialysis. Pretreatment plasma renin activity, insulin, epinephrine, norepinephrine, and dopamine levels were generally normal.
CONCLUSION: We conclude that in patients with terminal renal failure undergoing maintenance hemodialysis, intravenous bicarbonate is ineffective in lowering plasma potassium rapidly, and epinephrine is effective in only half the patients, whereas insulin in glucose is a fast and reliable form of therapy for hyperkalemic emergencies. Plasma aldosterone levels are appropriate in relationship to plasma potassium levels, and levels of other potassium-influencing hormones are generally normal.
AD
Department of Medicine, Kantonsspital, Aarau, Switzerland.
PMID
6
TI
Hypokalemic effects of intravenous infusion or nebulization of salbutamol in patients with chronic renal failure: comparative study.
AU
Liou HH, Chiang SS, Wu SC, Huang TP, Campese VM, Smogorzewski M, Yang WC
SO
Am J Kidney Dis. 1994;23(2):266.
To examine and compare the efficacy and safety of different routes of administration of salbutamol in treating hyperkalemia, 15 patients with chronic renal failure (blood urea nitrogen>80 mg/dL, serum creatinine>8.0 mg/dL) were enrolled to sequentially receive either intravenous infusion (0.5 mg) or nebulization (10 mg) of salbutamol. Five of these patients (33.3%) did not respond to the intravenous salbutamol and were excluded from the study. Both treatments significantly decreased plasma potassium in 10 patients and the decrease was sustained for at least 3 hours. After infusion, the maximal reduction in plasma potassium levels was 0.92 +/- 0.10 mEq/L and occurred after 30 minutes. On the other hand, the maximal reduction in plasma potassium after nebulization (0.85 +/- 0.13 mEq/L) was similar to that after infusion, but it occurred after 90 minutes. Insulin and blood glucose increased, whereas blood pH, PCO2, sodium, osmolality, and blood pressure did not change after either treatment. Heart rate increased significantly after both treatments, but less after nebulization than after infusion. It is concluded that both infusion and nebulization are simple, effective, and safe therapeutic modalities for the treatment of hyperkalemia in patients with chronic renal failure. Infusion should be used in patients requiring a rapid decrease in plasma potassium; nebulization, on the other hand, should be used in patients with coronary artery diseases.
AD
Department of Medicine, Veterans General Hospital-Taipei, Taiwan, ROC.
PMID
7
TI
Subcutaneous terbutaline use in CKD to reduce potassium concentrations.
AU
Sowinski KM, Cronin D, Mueller BA, Kraus MA
SO
Am J Kidney Dis. 2005;45(6):1040.
BACKGROUND: Acute hyperkalemia is a frequent and potentially life-threatening medical problem in patients on maintenance hemodialysis therapy. beta-Adrenergic receptor (betaAR) stimulation causes potassium cellular influx and a decline in plasma potassium concentrations. Therefore, betaAR agonists are used in the treatment of patients with hyperkalemia. The goal of this study is to evaluate the utility of weight-based subcutaneous terbutaline dosing to reduce plasma potassium concentrations in a group of subjects with chronic kidney disease (CKD) requiring hemodialysis.
METHODS: Fourteen subjects with CKD receiving long-term hemodialysis were administered terbutaline, 7 microg/kg, subcutaneously. Heart rate measurements and blood samples for potassium concentration determinations were made serially for 420 minutes. Effects of terbutaline on heart rate and potassium responses were determined in each subject.
RESULTS: Terbutaline significantly reduced plasma potassium concentrations and significantly increased heart rates during the time course of the study (P less than 0.001).  Mean reduction in peak potassium concentration (−1.31 ± 0.5 [SD] mEq/L) and increase in peak heart rate (25.8 ± 10.5 beats/min) were significantly different from baseline (P less than 0.001, baseline versus peak for both responses). No subject reported significant adverse effects. Conclusion: Administration of subcutaneous terbutaline obviates the need for intravenous access and should be considered as an alternative to nebulized or inhaled β-agonists to treat acute hyperkalemia in patients with CKD. As with the use of any β-adrenergic agonist, close cardiovascular monitoring is necessary to avoid or minimize toxicity during therapy.
CONCLUSION: Administration of subcutaneous terbutaline obviates the need for intravenous access and should be considered as an alternative to nebulized or inhaled beta-agonists to treat acute hyperkalemia in patients with CKD. As with the use of any beta-adrenergic agonist, close cardiovascular monitoring is necessary to avoid or minimize toxicity during therapy.

AD
Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Purdue University, Indianapolis, IN 46202-2879, USA. ksowinsk@iupui.edu
PMID

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