Effect of albuterol treatment on subsequent dialytic potassium removal. Effect of bicarbonate administration on plasma potassium in dialysis patients: interactions with insulin and albuterol. Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients. Salbutamol metered-dose inhaler with spacer for hyperkalemia: how fast? How safe? Low-potassium and glucose-free dialysis maintains urea but enhances potassium removal. Nebulized albuterol for acute hyperkalemia in patients on hemodialysis. Levalbuterol is as effective as racemic albuterol in lowering serum potassium. Treatment of hyperkalaemia by altering the transcellular gradient in patients with renal failure: effect of various therapeutic approaches. Effect of single dose resin-cathartic therapy on serum potassium concentration in patients with end-stage renal disease. Treatment of hyperkalaemia using intravenous and nebulised salbutamol. Comparison of aminophylline and insulin-dextrose infusions in acute therapy of hyperkalemia in end-stage renal disease patients. Increasing blood flow increases kt/V(urea) and potassium removal but fails to improve phosphate removal.
End-stage renal disease patients presenting with severe hyperkalemia are frequently treated with albuterol to lower their plasma potassium acutely, until emergent hemodialysis can be initiated. Such treatment stimulates potassium shifts from the extracellular to the intracellular fluid compartments. The resulting reduction of potassium concentration gradient between the blood and dialysate may potentially attenuate the efficacy of potassium removal during the ensuing hemodialysis treatment. To evaluate the effect of prior albuterol treatment on dialytic potassium removal, seven chronic hemodialysis patients were studied prospectively on two separate occasions. In one study the patients received 20 mg nebulized albuterol 30 minutes before dialysis; in the control study, albuterol treatment was omitted. Plasma potassium decreased 30 minutes after albuterol treatment (-0.84 +/- 0.06 mmol/L; P < 0.001) and remained unchanged in the corresponding period of the control experiment. Plasma potassium decreased during dialysis in both experimental protocols, but was significantly lower throughout dialysis in the albuterol study, as compared with the control study. Cumulative dialytic potassium removal was significantly lower following albuterol pretreatment compared with the control experiment (29.0 +/- 5.7 mmol v 49.6 +/- 7.0 mmol; P < 0.001). These observations suggest that acute albuterol therapy in patients with end-stage renal disease may substantially decrease potassium removal in the ensuing hemodialysis session. This may lead to rebound hyperkalemia several hours after the dialysis treatment. Acute treatment of hyperkalemia in patients with end-stage renal disease requires temporizing measures to shift potassium rapidly from the extracellular to the intracellular fluid compartments until hemodialysis can be initiated. Whereas insulin and albuterol are effective in lowering plasma potassium acutely, bicarbonate by itself is not. Bicarbonate administration may, however, potentiate the effects of insulin and albuterol on plasma potassium. Using a prospective cross-over design, we investigated the acute effects of (1) isotonic bicarbonate, (2) isotonic saline, (3) insulin + bicarbonate, (4) insulin + saline, (5) albuterol + bicarbonate, and (6) albuterol + saline on plasma potassium as well as blood bicarbonate and pH in nondiabetic hemodialysis patients. After obtaining a baseline blood sample, the subjects received one of the six treatment protocols, with plasma potassium measured every 15 minutes over 1 hour. Neither isotonic bicarbonate nor isotonic saline decreased plasma potassium significantly (-0.03 +/- 0.06 mmol/L v -0.01 +/- 0.10 mmol/L at 60 minutes; P = 0.60). Intravenous insulin decreased plasma potassium by a similar degree when given in conjunction with bicarbonate or saline (-0.81 +/- 0.05 mmol/L v -0.85 +/- 0.06 mmol/L at 60 minutes; P = 0.65). Likewise, nebulized albuterol decreased plasma potassium by a similar degree when given with bicarbonate or saline (-0.71 +/- 0.16 mmol/L v -0.53 +/- 0.15 mmol/L at 60 minutes; P = 0.18). The three protocols that included bicarbonate administration resulted in significant increases in blood bicarbonate (P < 0.005) and pH (P < 0.01), whereas the three protocols that included saline did not affect blood bicarbonate or pH. These observations suggest that bicarbonate administration does not potentiate the potassium-lowering effects of insulin or albuterol in hemodialysis patients. 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 is efficacious and safe for the acute treatment of hyperkalemia in hemodialysis patients. To determine the efficacy of inhaled salbutamol (rapidly delivered, using a metered-dose inhaler with a spacer device [MDI-S]) in lowering the serum potassium levels in patients with hyperkalemia.
                A randomized, double-blind, placebo-controlled trial.
                Seventeen chronic renal failure patients referred to the Nephrology Unit between October 1, 1997 and March 31, 1998 for hemodialysis were randomized.
                Group 1 received salbutamol followed by a placebo. Group 2 received a placebo followed by salbutamol. Each patient inhaled 1,200 microg salbutamol or a placebo through an MDI-S within 2 min. Blood samples were obtained repeatedly before inhalation and after 1, 3, 5, 10, and 60 min. The pulse rate and blood pressure were repeatedly measured. Insulin levels were examined in a subset of patients (n = 10) before, and 1 and 5 min following inhalation. Salbutamol's known side effects, palpitation, tachycardia tremor, and headache, were recorded. Potassium levels rose after 1 min following the completion of treatment and then decreased steadily thereafter. A rise of > or = 0.1 mEq/L was seen in 10 of 17 patients (59%) during the treatment period and there was no change (0%) seen during the placebo period (p < 0.0001). Within 3 min after inhalation of salbutamol, potassium levels declined as a function of time. Potassium levels in those patients taking the placebo did not change as a function of time (p < 0.001). The difference between the placebo and the salbutamol-treated periods reached significance after 5 min (p < 0.05). The serum glucose levels rose following inhalation of salbutamol, with a significant rise after 3 min. The heart rate rose significantly within the first 5 min following inhalation. Serum insulin levels remained unchanged 1 min after inhalation; however, after 5 min, a significant elevation was detected.
                Salbutamol inhalation of 1,200 microg, using an MDI-S, has a relatively rapid onset of action that induces a consistent reduction in serum potassium levels, starting 3 to 5 min following delivery. Unexpectedly, a paradoxical elevation was detected in serum potassium levels in the first minutes following inhalation. This effect, although minor (0.15 mEq/L above baseline), may cast some doubt on the role of salbutamol inhalation as the first treatment for excessive hyperkalemia. The influence of potassium (K) removal on dialysis efficiency as measured by urea elimination is not clear. In this prospective, randomized, cross-over study we investigated the magnitude of K removal and its effect on urea (u) elimination during high-flux haemodialysis (HD).
                Twelve stable, non-diabetic HD patients were investigated during three one-week standardized HD periods (1.8 m(2) high-flux polysulphone dialyser, treatment time 240 min, Qb = 300 ml/min, Qd = 500 ml/min, dialysate without glucose, bicarbonate 40 mmol/l), using dialysates containing 0 (0K), 1 (1K), and 2 (2K) mmol/l of K. Mass removal of K (M(K)) and u (M(U)) were measured during the mid-week treatment by partial dialysate collection. Urea reduction rate (URR) and Kt/V were determined.
                0K, 1K and 2K treatments were perfectly comparable. Plasma K (PK) continuously declined reaching stable concentrations after 180 min. While 0K dialysate removed 117.1 mmol, 80.2 and 63.3 mmol (P < 0.001) were removed by 1K and 2K baths respectively. M(U) was not influenced by M(K) (r = 0.22) and amounted to 491.1 (0K), 508.6 (1K), and 506.2 (2K) mmol (NS) respectively. Accordingly, urea clearance, URR and Kt/V were constant during 0K, 1K and 2K treatments.
                Potassium-free dialysate significantly enhances potassium elimination. Potassium removal has no influence on urea elimination. High potassium removal, when needed, does not impair dialysis efficiency as measured by urea kinetics in high-flux, glucose-free, 40 mmol/l bicarbonate HD. To determine the efficacy and safety of nebulized albuterol in the acute treatment of hyperkalemia in patients on chronic hemodialysis.
                Prospective, double-blind, and placebo-controlled study.
                Outpatient hemodialysis clinic at a university medical center.
                Ten patients on maintenance hemodialysis who had chronic hyperkalemia.
                Patients received nebulized albuterol therapy (10 mg or 20 mg) or placebo (saline) on three separate occasions, serial measurements of plasma potassium levels, blood pressure, and pulse were then taken for a 2-hour period.
                Patients had a significant decrease in plasma potassium concentrations that was evident by 30 minutes and sustained for at least 2 hours after albuterol treatment. After the administration of 10- and 20-mg doses of albuterol, the maximal decrease in the plasma potassium levels was 0.62 +/- 0.09 and 0.98 +/- 0.14 mmol/L (SE), respectively. Nebulized saline administration did not produce a significant change in the plasma potassium concentrations. Patients did not develop symptoms or significant changes in blood pressure or heart rate with albuterol treatment.
                In the doses used, nebulized albuterol therapy resulted in a prompt and significant decrease in the plasma potassium concentrations in patients on hemodialysis, and caused no adverse cardiovascular effects. This treatment should be considered as an important adjunct for acute treatment of serious hyperkalemia in this population of patients. Albuterol is an effective treatment for hyperkalemia through beta-adrenergic induction of potassium (K+) uptake. Levalbuterol, the R-enantiomer of racemic albuterol, is used for the treatment of asthma and 0.63 mg of levalbuterol has the same therapeutic efficacy as 2.5 mg of albuterol but with a decreased adverse effects profile. We hypothesized that levalbuterol can reduce serum K+ levels similarly to albuterol when used in equipotent doses. In a randomized, double blind, placebo-controlled prospective study, we compared the K+-lowering effects of nebulized saline and equipotent bronchodilatory doses of albuterol (10 mg) and levalbuterol (2.5 mg) in healthy adult volunteers. Nine subjects entered each of the three study groups. Serum K+ was measured at baseline, at 30 min (immediately after treatment), at 60 min, and at 90 min. All adverse effects were recorded. The three groups had similar baseline K+ values. Immediately after nebulization, only levalbuterol showed a significant decrease in potassium level (p = 0.024). At 30 and 60 min after treatment, both albuterol and levalbuterol groups had significantly lower K+ values compared to placebo. No significant difference occurred between the albuterol and levalbuterol groups. Levalbuterol caused fewer reported adverse effects compared to albuterol. Ten patients with acute and 60 with chronic renal failure (both groups having hyperkalaemia), were managed at Kenyatta National Hospital in the medical wards and Renal Unit between August, 1995 and January, 1996. They were divided into seven different treatment groups, each consisting of ten patients. Treatment A glucose 25g i.v. with insulin 10 units i.v., treatment B 50 mmol of 8.4% sodium bicarbonate infusion, treatment C 0.5mg of salbutamol i.v. in 50mls 5% dextrose, treatment D was a combination of treatments A and B, treatment E was a combination of treatment B and C, treatment F was a combination of treatments A and C while treatment G was a combination of treatments A and B and C. Serum potassium was measured, 30 minutes, 1 hour, 2 hours, 4 hours and 8 hours after treatment. Plasma glucose concentration was measured before treatment was given and 1 hour after in all patients. Electrocardiography was done before treatment on all patients and repeated 30 minutes and 1 hour after treatment for the patients with hyperkalaemic changes on the initial recording. All treatment modalities had satisfactory potassium lowering effects. Of the single therapeutic approaches, treatment A and C were equieffective, but better than treatment B (P < 0.001). Amongst the two regimen combinations, treatment D and F were more efficacious than treatment E and all the single therapeutic approaches (P < 0.001). Treatment G was the most efficacious in lowering serum potassium in this study. All treatment modalities had maximum serum potassium lowering effect at 1-2 hours. A fall in plasma glucose concentration was a notable feature of treatments A and D, but significant hypoglycaemia occurred in 20% of patients receiving treatment A and in none on treatment D. The ECG changes of hyperkalaemia did not correlate with serum potassium levels. The normalisation of hyperkalaemic ECG alteration occurred within the first 30 minutes after treatment. In conclusion, combination therapies for hyperkalaemia appear to be more efficacious than single therapeutic approaches. Inclusion of salbutamol seems to protect against insulin induced hypoglycaemia. The maximum potassium lowering effect is observed 1-2 hours of administration of either agents. The potassium reducing effect remains significant compared to baseline values even after 8 hours. If dialysis cannot be instituted early enough it seems reasonable to repeat treatment every 4-6 hours to sustain the effect. Repeated administration of glucose with insulin may not be safe because of the hypoglycaemic effect. Other single and combination therapies can theoretically be repeated regularly until dialysis is initiated although this requires further clinical evaluation. Hyperkalemia in patients with renal failure is frequently treated with a cation exchange resin (sodium polystyrene sulfonate, hereafter referred to as resin) in combination with a cathartic, but the effect of such therapy on serum potassium concentration has not been established. This study evaluates the effect of four single-dose resin-cathartic regimens and placebo on 5 different test days in six patients with chronic renal failure. Dietary intake was controlled. Fecal potassium output and serum potassium concentration were measured for 12 h. Phenolphthalein alone caused an average fecal potassium output of 54 mEq. The addition of resin caused an increase in insoluble potassium output but a decrease in soluble potassium output; therefore, there was no significant effect of resin on total potassium output. Sorbitol plus resin caused less potassium output than phenolphthalein plus resin. On placebo therapy, the average serum potassium concentration increased slightly (0.4 mEq/L) during the 12-h experiment. This rise was apparently abrogated by some of the regimens that included resin; this may have been due in part to extracellular volume expansion caused by absorption of sodium released from resin. Phenolphthalein regimens were associated with a slight rise in serum potassium concentrations (similar to placebo); this may have been due to extracellular volume contraction produced by high volume and sodium-rich diarrhea and acidosis secondary to bicarbonate losses. None of the regimens reduced serum potassium concentrations, compared with baseline levels. Because single-dose resin-cathartic therapy produces no or only trivial reductions in serum potassium concentration, and because this therapy is unpleasant and occasionally is associated with serious complications, this study questions the wisdom of its use in the management of acute hyperkalemic episodes. In 11 children (aged 5-18 years) with end stage chronic renal failure, the effect on plasma potassium of two doses of salbutamol (separated by two hours) given intravenously (4 micrograms/kg) and on a separate date, of salbutamol administered by nebuliser (2.5 mg if the child weighed below 25 kg, 5 mg if above) was observed. Within 30 minutes of the first dose, the mean plasma potassium concentration fell significantly by 0.87 and 0.61 mmol/l after intravenous and nebulised administration respectively. Sixty minutes after the second dose the plasma potassium was significantly reduced by a further 0.28 and 0.53 mmol/l respectively. There was a significant difference between the two methods of administration at 300 minutes after the first dose favouring nebulisation. No major side effects were observed. Nebulised salbutamol should be the first choice emergency treatment of hyperkalaemia. This study was performed to compare the efficacy of aminophylline and insulin-dextrose infusion as acute treatment modality of hyperkalemia in patients with end-stage renal disease (ESRD).
                This study was conducted on 30 ESRD patients with serum potassium > 6.0 mEq/L. These patients were divided in two groups of 15 each. Group A patients were treated with aminophylline infusion, whereas group B patients were treated with insulin-dextrose infusion. Serum potassium and other biochemical parameters such as blood sugar were measured at beginning of treatment followed by at 60 minutes, 180 minutes, and 360 minutes after treatment.
                Intervenous infusion of aminophylline lowered plasma potassium from 6.48 +/- 0.39 mEq/L to 5.92 +/- 0.40 mEq/L at 180 minutes (p < 0.001 Vs basal) and 6.05 +/- 0.53 mEq/L at 360 minutes (p < 0.01 Vs basal). Whereas, intravenous infusion of insulin-dextrose decreased plasma potassium from 6.59 +/- 0.31 mEq/L to 5.76 +/- 0.32 mEq/L (p < 0.001 Vs basal) and 5.84 +/- 0.21 mEq/L (p < 0.001 Vs basal). Thus in both groups, plasma potassium levels were significantly less than basal levels throughout the study. The decrease in plasma potassium was significantly more in group B patients (p value is < 0.001 after 60 minutes, < 0.05 after 180 minutes and < 0.05 after 360 minutes) when compared to group A patients. There was one episode of hypoglycemia (blood sugar < 60 mg%) in insulin-dextrose infusion group. No other side effects were observed throughout the study.
                Aminophylline is an effective modality for acute treatment of hyperkalemia, though it is less effective than insulin-dextrose infusion. However, more studies are required to confirm these results. Hyperphosphatemia and hyperkalemia are major determinants of morbidity and mortality in hemodialysis patients. Half of the dialysis population suffers from hyperphosphatemia which is now recognized as an important cardiovascular disease risk factor. It is, therefore, necessary to improve the removal of these molecules. In this study, we investigated the effect of enhancing blood flow on Kt/V for urea (Kt/Vu), potassium and phosphate removal.
                Thirteen patients were investigated in a randomized, cross-over, prospective study using 3 blood flows (Qb) of 200,250 and 300 ml/min which gave 39 standardized high-flux hemodialysis treatments. Effective blood flows were measured by ultrasonic flow meter. Quantification of delivered dialysis dose was performed by partial dialysate and ultrafiltrate collection for the determination of potassium and phosphate removal and by blood urea concentrations for determination of Kt/Vu.
                Kt/Vu rose significantly from 1.10 +/- 0.14 to 1.22 +/- 0.14 and finally to 1.39 +/- 0.16 (p = 0.0001) with increasing Qb similar to the increase in potassium removal from 53.0 +/- 2.4 to 63.4 +/- 2.6 and to 74.2 +/- 3.8 mMol (p = 0.01). Phosphate removal only improved from 28.1 +/- 1.3 to 31.4 +/- 1.5 (p = 0.050) when Qb was increased from 200 to 250 ml/min but remained unchanged at 31.2 +/- 1.5 mMol (NS compared to phosphate removal at Qb = 250 ml/min) when Qb was increased to 300 ml/min.
                Increasing delivered Kt/Vu and potassium removal with higher Qb fails to produce the same desired effect with phosphate removal during high-flux hemodialysis.
Nebulised or inhaled salbutamol, or IV insulin-and-glucose are the first-line therapies for the management of emergency hyperkalaemia that are best supported by the evidence. Their combination may be more effective than either alone, and should be considered when hyperkalaemia is severe. When arrhythmias are present, a wealth of anecdotal and animal data suggests that IV calcium is effective in treating arrhythmia. Further studies of the optimal use of combination treatments and of the adverse effects of treatments are needed.