Documente Academic
Documente Profesional
Documente Cultură
Michael Allon3
Renal
Disease:
Mechanisms
6:1134-1
142)
ABSTRACT Clinical investigations in the past few years hove 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 fradrenergic 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 hyperkalemla In patients with ESRD, including prolonged fasting and the use of noriselective p-adrenergic blockers. These new insights may improve the clinical management of hyperkalemla in patients with renal failure. Key Words: Potassium,
bonate
insulin,
albuterol,
epinephrine,
bicar-
temporizing measures are used. Mter the myocardium is stabilized with intravenous calcium, therapy is directed at decreasing plasma potassium acutely, by shifting potassium from the extracellular to the intracellular fluid compartment. Until recently, the administration of intravenous insulin and bicarbonate was recommended uniformly to promote this shift. Only in the past few years have these textbook recommendations been examined critically In carefully designed, prospective studies. These investigations have confirmed the efficacy of insulin, while casting doubts about the utility of bicarbonate therapy. Moreover, these studies have established 13-adrenergic agonists as useful adjuncts to insulin for the acute treatment of hyperkalemla. The following section will examine some of the studies that have led to a change in our thinking. To understand the rational treatment and prevention of hyperkalemia in ESRD patients. It is necessary to understand the physiologic mechanisms that regulate potassium homeostasls. Extracellular potassium concentration Is determined by two distinct regulatory systems (3) (Figure 1). The first system maintains external potassium balance by regulating potassium excretion according to dietary intake. On a typical American diet containing approximately 100 mmol of potassium per day, 90 to 95 mmol Is excreted by the kidneys and 5 to 10 mmol is excreted by the gut. The excretion of an acute potassium load is a relatively slow process, requiring several hours for completion (4). In ESRD patients, there is an adaptive Increase in potassium excretion by the gut (5-9). Nevertheless, this adaptation is insufficient to compensate for the loss of renal excretory capacity. The second homeostatic system maintains internal potassium balance by regulating potassium shifts between the intracellular and extracellular fluid compartments. Internal balance can be achieved much faster than external balance: an acute potassium load Is shifted into the cells within minutes (2). Total body potassium is about 3.300 mmol. Only 2% (about 65 mmol) Is in the extracellular fluid compartment, whereas 98% Is in the intracellular fluid compartment, primarily in skeletal muscle and to a lesser extent In liver. This uneven distribution means that relatively small shifts of potassium from the intracellular to the extraceilular fluid compartment can produce severe hyperkalemla. Conversely, relatively small potassium shifts from the extracellular to the intracellular fluid compartment can produce a marked decrease in plasma potassium. Extrarenal
potassium disposal (shifts from the extracellular to
ecent review articles have discussed in depth the pathogenesis and management of potassium disorders in patients with ESRD (1,2). The goal of this editorial review Is to focus primarily on recent clinical investigations that have enhanced our understanding of potassium homeostasis in hemodialysls patients and to consider their Implications for the treatment and prevention of hyperkalemla in dialysis patients.
OF HYPERKALEMIA
IN ESRD
in by
hemodialysis. Involves
7, 1995.
the delay,
1995. 27th
Received
February
Society
Birmingham,
April 26,
at
2The
American
manuscript
was
presented
the
annual
meeting
1994).
of
the
3Corresponderrce
Street,
Journal
(October of Nephroiogy,
26-29,
19th
1046.6673/0604-1
134$03.00/0
American 1995 by the
of
the
Society
American
Copyright
the
intracellular
fluid
compartment)
assumes
a criti-
1134
Volume
Number
1995
Allon
Plasma mmol/L
Potassium,
B,carbonate
Epoephr.ne
insuhn/glucose
-1
O-
STOOL 5-10E/day
D,aiyss
-1
5O 10 20 30
of
1#{149}
Figure 1. Internal and external potassium balance In humans. Reproduced with permission from Ref. 3. Gl, gastrointestinal; RBC, red blood cells.
40
Treatment,
50
60
mm
Duration
role in the defense against hyperkalemia In ESRD patients. The two major physiologic factors that stimulate extrarenal potassium disposal are insulin and epinephrine. Flatman and Clausen (10) observed the stimulation of potassium Influx in isolated skeletal muscle fibers incubated with insulin or epinephrine. Simultaneous exposure to both hormones produced an additive effect on potassium Influx, suggesting different cellular mechanisms. These observations would suggest that both insulin and epinephrine may be useful for the treatment of hyperkalemia In dialysis patients. Whereas Insulin is routinely used for this purpose in clinical practice. epinephrine is not. The potassium-lowering effect of insulin in normal individuals is well established and dose dependent; It is increased progressively, going from moderate physcal iologic doses to high physiologic doses to phannaco-
Figure 2. Changes in plasma potassium during the Intravenous infusion of 8.4% bicarbonate, epinephrine, or Insulin In glucose and during hemodialysis. Values represent means SE. Reproduced with permissIon from Ref. 16.
logic doses (11). The effect of insulin on potassium uptake Is distinct from that of eplnephrine. because p-adrenergic blockade does not attenuate the decrease in plasma potassium during insulin administration (12,13). Several studies have documented the efficacy of intravenous insulin in the acute treatment of hyperkalemia in ESRD patients (14-17) (Figure 2). The magnitude of decrease in plasma potassium after insulin administration In hemodialysis patients is comparable to that obtained in normal controls (14). Interestingly, the effect of insulin on cellular potassium uptake can be dissociated from its effect on glucose uptake. This dissociation was demonstrated In an elegant clinical study that measured plasma potassium In the brachial artery and vein of normal controls before and during a continuous infusion of insulin into the brachial artery (18). Insulin increased
the arteriovenous gradIent for both potassium and
glucose.
However,
the
concomitant
Infusion
of
ouabaln with insulin prevented the stimulation of potassium uptake, without affecting glucose uptake. Thus, the effect of Insulin on potassium uptake appears to be mediated by enhanced activity of the Na-K pump, whereas the stimulation of glucose uptake is achieved by a membrane-bound glucose transporter (19). These two effects of insulin are often dissociated In hemodialysis patients. As a result, ESRD patients are relatively resistant to the glucose-lowering effect of insulin (20-22), yet responsive to Its potassium-lowering action (14). When treating hyperkalemia, dextrose is routinely administered in conjunction with Insulin, to avoid the anticipated hypoglycemia. Because exogenous glucose stimulates endogenous insulin secretion, one might be tempted to administer dextrose alone. Such an approach is ill advised in the emergent situation. If endogenous insulin Is not secreted (as might occur in insulin-dependent diabetics or in patients with inadequate insulin reserve), the resulting hyperglycemia Is likely to aggravate the hyperkalemla (23-26). An acute worsening of hyperkalemia Is not unique to hyperglycemia; any maneuver that increases plasma osmolalIty promotes potassium shifts from the intracellular to the extracellular fluid compartments. Thus, for example, acute Infusions of mannitol, hypertonic saline, and hypertonic arginine in dialysis patients also raise plasma potassium acutely (27-29). The hyperkalemic effect of hyperosmolality Is independent of changes in plasma insulin, cartecholamines, or acid-base status (28). Epinephrlne at physiologic doses produces hypokalemla acutely In normal controls (30-34). The stimu-
Journal
of the American
Society
of Nephrology
1135
Hyperkalemia
in ESRD
of extrarenal potassium disposal by epinephrine is mediated by J3-2 adrenergic receptors. It is prevented by /3-2 selective blockers and by nonselective /3 blockers, but not by /3-1 selective blockers (30.32,35). The ability of intravenous /3-2 agonists to induce hypokalemla in normal IndivIduals (36,37) suggests their potential utility for acute therapy of hyperkalemla in hemodlalysls patients. Montoliu eta!. (38) first reported that intravenous albuterol (0.5 mg),
latlon
a /3-2 agonIst, acutely lowers plasma potassium in
hemodialysls patients. The effect was maximal (1.1 mmol/L reduction) at 30 mm and was sustained for at least 3 h. In several patients, hyperkalemic electrocardiographic changes resolved after the administration of albuterol alone, in the absence of Intravenous calcium or any other measures to lower plasma potassium. Subsequent studies have confirmed the efficacy of Intravenous albuterol In the acute treatment of hyperkalemla In patients with renal failure (17,39,40). Neither albuterol nor any other /3-2 selective agonist Is available for Intravenous use In the United States. However, selective (3-2 agonists are available in nebulized form for the treatment of asthma. Moreover,
nebullzed albuterol (and other /3-agonists) produces
eightfold higher than those used to treat asthma. raising concerns about potential adverse cardiovascular effects. The mean increase in heart rate in our double-blinded study was 6 beats/min with 10 mg of albuterol and 8 beats/min wIth 20mg of albuterol (45) (Figure 3). There were no significant changes in blood pressure, and no patient developed chest pain or arrhythmias. Several subsequent investigations have similarly reported stable blood pressures and clinically insignificant Increases in heart rate after the nonblinded administration of albuterol at similar nebulized doses to ESRD patients (15,40,46). An increase in plasma glucose after intravenous and nebulized albuterol has been observed in a number of studies, but this has not been clinically significant (-2 to 3 mmol/L). A direct comparison between intravenous (0.5 mg) and nebullzed (10 mg) albuterol in ESRD patients revealed a similar magnitude of decrease in plasma potassium (40). The onset of the potassium-lowering effect was somewhat slower with the nebulized drug than with the intravenous form. On the other hand,
nebulized aibuterol produced less tachycardia than
hypokalemla in normal controls (4 1-44). Indicating significant systemic absorption of the inhaled drug. To determine whether nebulized albuterol was useful for the acute treatment of hyperkalemla in ESRD patients, we studied ten hemodialysis patients In a double-blinded, crossover trial (45). Each subject received 10 or 20 mg of nebulized albuterol or nebulized placebo (saline) inhaled over 10 mm. Plasma potasslum decreased by about 0.6 mmol/L after 10 mg of albuterol and by about 1.0 mmol/L after the 20-mg dose (Figure 3). A significant decrease In plasma potassium was first noted after 30 mm. Albuterol was equally efficacious in diabetic and nondlabetic patients. In contrast, nebulized placebo did not lower plasma potassium. Subsequent studies have confirmed the utility of nebulized albuterol (10 to 20 mg) In lowering plasma potassium acutely (15.40,46). -J The doses of albuterol required to achieve a significant reduction in plasma potassium are fourfold to
the intravenous form. Thus, nebulized albuterol may be safer than the intravenous form in patients with known or suspected coronary artery disease. It Is Important to note that a subset of ESRD patients are refractory to the potassium-lowering effect of albuterol (K 0.4 mmol/L). In various studies, these have ranged from 20 to 40% of dialysis patients studied (15,40.45). Similarly. even pharmacologic doses of epinephrine do not lower plasma potassium in some dialysis patients (47.48). The reason for this resistance has not been elucidated. Because we cannot prospectively Identify which patients are resistant to albuterol, It Is critical to treat severe hyperkalemla with intravenous insulin, as well as albuterol. The potassium-lowering effect of albuterol in ESRD patients Is additive to that of insulin. We found that Intravenous insulin (10 U bolus) and albuterol (20 mg nebulized over 10 min) each lowered plasma potassium by approxImately 0.6 mmol/L, whereas in combination, they lowered plasma potassium by about 1.2
I
Figure 3. The effect of nebulized
1136
30
60
Time,
90 minutes
120
TIme,
minutes
albuterol in doses of 10 mg (solid bar) or 20 mg (stippled bar) or of nebulized placebo (open bar) on the plasma potassium concentration (left panel) and heart rate (right panel) of hemodlalysis patients. Values represent means SE. P < 0.05 versus nebulized placebo. p < 0.05 versus 10 mg of albuterol. Adapted from Ref. 45.
Volume
6-
Number
1995
Allon
mmol/L (15). A similar additive effect has also been reported with intravenous albuterol and Insulin (17). This additive effect is consistent with the in vitro observations in isolated skeletal muscle fibers (10). Albuterol may also attenuate insulin-induced hypoglycemia in hemodialysis patients. Dextrose is administered routinely with intravenous Insulin to prevent the predictable hypoglycemia. Nevertheless, hypoglycemia (frequently asymptomatic) may be a common event after such therapy. For example, we documented hypoglycemia (plasma glucose < 3 mmol / L) in 9 of 12 hemodialysis patients 1 h after they received 10 U of regular insulin and 25 g of dextrose as an intravenous bolus (15). The high incidence of hypoglycemia may reflect, in part, a defect in the activation of counterregulatory sympathetic discharge m ESRD patients (49). When nebulized albuterol was given concurrently with the same regimens of insulin and dextrose, only 2 of 10 patients developed hypoglycemia. This salutory action of albuterol is likely mediated by the $3-adrenergic stimulation of gluconeogenesis (50). In contrast to /3-adrenergic stimulation, which enhances potassium influx into the cells, a-adrenergic stimulation enhances potassium efflux out of the cells (51.52). Hence, the effect of epinephrine, a mixed aand /3-blocker, on plasma potassium reflects the relative effects of a- and /3-adrenergic stimulation on
plasma potassium. Hemodialysls al. (34) (0.015 patients are that
resis-
?
E
0.41
Alpha
Beta
cm
0.2
#{149} Transplant
___
Dialysis
Control
II!
0.04
Pure Alpha
0.8
0
E E
to 0 a.
a, cm C
to
C 0
tant For
effect
of epinephrlne.
a low
found
kg per min) lowered plasma potassium by about 0.4 mmol/L In normal controls but had no effect in hemodialysis patients. Similarly, Blumberg et at. (16) observed no significant change In plasma potassium during the infusion of epinephrine at high physiologic doses (0.05 pg/kg per min) in hemodIalysis patients (Figure 2). These findings are in contrast to the potassium-lowering effects of /3-2 agonists in ESRD patients, suggesting a possible imbalance between a- and /3-adrenergic effects on potassium In dialysis patients.
physiologic To evaluate this possibility, we gave ESRD patients and normal controls at three physiologic
g/
-J
0
E
E E
tn
U,
a 0
0.
C a, C r
to
cm
a graded
doses
(33).
In normal
controls,
Infusion of epinephrmne (0.01 to 0.04 ,.tg/kg per mm) increasing doses of epmnephgreater decreases in hemodialysis in pa-
0.01 Epinephrine
0.02
0.04
dose (ig/kgJmin)
progressively In contrast,
Figure
(means
4. Changes
SE) from
tients, epmephrine at the lowest dose actually increased plasma potassium, suggesting a predominant a-adrenergic effect. Even the highest dose of epinephnine did not significantly decrease plasma potassium
in ESRD patients (Figure 4). To indirectly assess the
nous epinephrine at three doses in normal controls, hemodialysIs patients, and renal transplant patients (serum creatmine <2 epinephrlne
a-adrenergic component of epinephrine, the identical infusion protocol was repeated during concurrent /3 blockade with propranolol. a-Adrenergic stimulation raised plasma potassium in a dose-dependent manner in both experimental groups. The magnitude of this increase was significantly greater. however, in dialysis patients (0.7 mmol/L) than in normal controls (0.3 mmol/L). Finally, the concomitant infusion of the
plus f3-adrenerglc stimulation), the middle panel shows the effect of epmnephrlne during $3 blockade (pure a effect), and the lower panel shows the calculated pure /3 effect. The changes in potassium in the upper and middle panels were signifIcantly (P < 0.05)
(a-
mg/mi). alone
The
upper
panel
shows
the
effect
of
different In the dialysis patients as compared with those in the controls and transplant patients. Reproduced with per-
Journal
of the
American
Society
of Nephrology
1137
Hyperkalemia
in ESRD
a-blocker phentolamine overcame the resistance to the potassium-lowering effect of epinephrine in the dialysis patients (33). In summary, these studies suggest that the resistance to the potassium-lowering
effect of epmnephrmne In hemodlalysis patients Is due to
Whether
ate
a similar synergism exists between adrenerglc agonists is unknown. The removal of potassium by hemodialysis
and (3-2 by the
bicarbonis largely
determined
between
sures that
the
plasma
acutely
an enhanced a-adrenerglc response. Interestingly, this acquired resistance Is reversed after successful renal transplantation (2) (FIgure 4). Bicarbonate therapy has long been assumed to be effective for the acute treatment of hyperkalemia In dialysis patients. It is presumed that the metabolic
acidosls stimulating lar to the of renal net failure potassium promotes shifts hyperkalemia from the intracelluby
lular duce
that the is
acute raises no
to the intracellular fluid compartment will rethis gradient and thereby attenuate potassium removal by the subsequent dialysis treatment. Such an effect of insulin is suggested by studies demonstrating less dialytic potassium removal with glucosecontaining dialysate as compared with glucose-free dialysis (64). Thus, one might anticipate that aggressive therapy with insulin and albuterol for hyperkalemia may attenuate the removal of potassium in the subsequent dialysis treatment. Such a phenomenon
might potentially lead to a rebound hyperkalemia
several
hours
after
the
dialysis
session.
potassium,
acids
have
effect (53-56). The effect of acute acid administration on plasma potassium in dialysis patients has not been reported. Acute (1- to 3-h) bicarbonate administration to nephrectomlzed animals has lowered plasma potassium in some studies (56,57), but not in others (54,55). SodIum bicarbonate infusion in hyperkalemic
dialysis patients lowers plasma potassium after 6 to 24 h (58). However, to be useful for acute therapy, the changes should occur within about 1 h. Blumberg et a!. (16) found that neither hypertonic nor isotonic
PREVENTION
Given
potassium clearly
OF HYPERKALEMIA
IN ESRD PATIENTS
central role of the kidneys in maintaining homeostasis. dietary potassium restriction plays an Important role in the prevention As nephrologists, we whenever we encounter
patients. We then ask
the
of
bicarbonate (hypertonic there was no significant in ESRD patients, dein plasma bicarbonate
(59). In fact, serial plasma potassium measurements for 6 h after bicarbonate administration found the earliest decrease at 4 h (60). In summary, although bicarbonate administration lowers plasma potassium chronically In ESRD patients. It does not do so in a
timeframe useful for the emergent treatment of hy-
provide the patients with appropriate dietary guidelines. It Is important, however, to recognize some nondietary factors that may predispose to hyperkalemia in hemodialysls patients. Thus, for example, there is convincing evidence for the impairment of extrarenal potassium disposal in ESRD patients. In a recent study, we gave fasted hemodialysis and control subjects a small oral potasslum load (0.25 mmol/kg, or about 20 mmol for an 80-kg patient). The mean increase in plasma potassium was substantially greater In hemodialysis patients than in controls (0.8 versus 0.4 mmol/L) and
perkalemia. Of course, bicarbonate therapy Is still indicated for the acute management of severe metabolic acidosis. A recent abstract suggested that bicarbonate administration may potentiate the potassium-lowering action of Insulin in hemodialysis patients (61).
Whereas bicarbonate administration by Itself had no
could not all be accounted for by renal excretion (65). Similar observations were reported by Fernandez et at. (66). These clinical observations in ESRD patients are also in agreement with the impairment of ouabamninhibitable rubidium uptake by skeletal muscle from uremic rats (67,68). Patients do not usually eat potassium by itself. They
eat foods that contain drate. The endogenous potassium, insulin as well that is as carbohyreleased in
potassium after 60 min In eight hemodialysis patients, It enhanced the potassium-lowering effect of insulin. Plasma potassium was decreased by 0.6 mmol/L after insulin alone and by 1.0 mmol/L after insulin plus bicarbonate. The cellular mechanism of this synergIsm Is unexplained but may Involve pH-dependent changes in the insulin receptor. If this study Is confirmed, It may provide a rationale for the administration of bicarbonate for the acute treatment of hyperkalemla in ESRD patients.
significant
effect
on plasma
response to the carbohydrate promotes extrarenal potassium disposal. We found that the ingestion of 50 g of glucose along with an oral potassium load (0.25 mmol/kg) attenuated the mean rise In plasma potassium from 0.8 to 0.3 mmol/L (65). If one assumes that the extracellular fluid compartment is approximately 20% of total body water and that all the ingested potassium (0.25 mmol/kg) remains in the extracellular fluid compartment, then one would predict a 1.25 mmol/L increase in plasma potassium. The actual measured increases suggest that endogenous insulin
approximately doubles extrarenal potassium dis-
1138
Volume
Number
1995
Allon
posal.
constitutes
from
36
to after
76%. an oral
Thus,
dietary
against
carbohydrate
life-threatening load in dialysis
0
a major
defense
4.8
hyperkalemia patients.
potassium
The ability of exogenous insulin to lower plasma potassium acutely has been discussed earlier. What Is less well appreciated is that even the low circulating
,g.
E
U,
U,
4.6
4.2
insulin concentrations present during prolonged fasting constitute an important defense against hyperkalemia. Thus, the Inhibition of endogenous insulin secretion in normal, fasting controls results in a
significant insulin increase levels may in plasma potassium (69). be particularly important hyperkalemia is suggested in dialysis Fasting in the patients.
U,
0
a.
U,
3.8
3.6 3.4
-I
E
.!
0.
0)
#{149}
somatostatin
a greater
administration in plasma than in control animals (68). The decrease in plasma insulin
increase transition from is not sufficient a postprandial to raise plasma
by the finding that acute to fasting rats produced potassium in uremic rats that occurs in the
12
18
30,
the by
to
.E
0,
20
func-
hyperkalemia. Thus, Gifford et a!. (34) fasted nondlabetic hemodlalysis patients and normal controls for 26 h. Plasma potassium increased by about 0.5 mmol / L in ESRD patients but did not change in the controls. This observation suggests that prolonged fasting may be an Important cause of hyperkalemia
when hemodialysis diagnostic procedure. patients are fasted for surgery or a
I
the
i:
V
I
#{149}
6 Hours
12 of Fasting
18
To be
determine prevented
by
could fasted 10
mea(70).
hemodialysis plasma
On a second continuous
occasion, the same patients received a infusion of 10% dextrose with 20 U of regular insulin per liter, infused at 50 mL/min (or 1 U of insulin/h). This insulin infusion regimen doubled
fasting pletely sium doses plasma insulin from 10 to 20 mU/L prevented the 0.6 mmol/L increase observed during fasting (Figure 5). of exogenous insulin can potentially and comin potasEven low
Figure 5. Serial plasma potassium and Insulin concentrations during an 18-h fast in hemodlalysis patients In the absence (solid squares) or presence (open squares) of a continuous physiologic infusion of insulin (1 U/h) with dextrose (5 glh). Values represent means SE for 10 patIents. p < 0.05 and P < 0.01 versus the value at 6 h of fasting; P < 0.01 versus
corresponding value In the control experiment. Repro-
duced
fasting
with permission
plasma Insulin
produce evaluate whether exogenous glufasting hyperkalemla. by stimulating endogenous Insulin secretion, we restudied some patients with an infusion of 10% dextrose alone. This attenuated the rise in plasma potassium during prolonged fasting but was not as effective as dextrose with insulin (70). Hyperkalemla is much less common In patients on continuous ambulatory peritoneal dialysis than In hemodialysis patients (71). This Is due, in part, to the hypoglycemia. cose can prevent To
continuous removal of potassium with continuous
moting extrarenal potassium disposal (72,73). Because /3-2 agonists decrease plasma potassium, one might expect /3-blockers to increase plasma potas-
sium. This is not a significant problem in individuals with normal renal function, because potassium transferred from the intracellular to the extracellular fluid compartment can be excreted by the kidneys. In the absence of renal excretory function, /3 blockade can aggravate hyperkalemia in ESRD patients. Thus, for example, a 10-day course of propranolol, a nonselective /3-blocker, increased predlalysis potassium by 0.7
ambulatory peritoneal dialysis. However, another contributory factor Is the continuous absorption of glucose from the dialysate, which results in increased
mmol/L In a group of hemodialysis patients. trast, the /3-1 selective blocker atenolol did crease plasma potassium in the same group
tients (74). Similarly, exercise-induced
In connot inpa-
of hyperkalemla
in ESRD
patients
is augmented
by
the
nonselective
Journal
of the American
Society
of Nephrology
1139
Hyperkalemia
in ESRD
/3-adrenergic
the /3-1
blocker
selective
propranolol
blocker metoprolol
but prescribe
is not
(75)
affected
(Figure
by
6).
TABLE 1. Changing concepts in the management hyperkalemia in dialysis patients Conventional Wisdom New Wisdom
of
/3-1 selectIve
A recent abstract described the potential utility of chronic oral 13-adrenerglc administration (albuterol, 2 mg twice daily) In the prevention of hyperkalemla in hemodialysis patients (76). The predialysis plasma potassium was decreased by 0.6 mmol/L after 2 wk of
oral
from and
albuterol.
the study
However,
because
3 of the
12 patients
withdrew
palpitations Insulin decreases plasma
Bicarbonate is not effective for acute therapy of hyperkalemla. Albuterol decreases plasma potassium acutely.
Insulin decreases plasma
of unacceptable
tremor. Further studies are indicated to evaluate this prophylactic measure In hemodialysis patients with persistent hyperkalemia not responsive to dietary potassium restriction. Mlneralocorticolds play an important role In maintaining potassium and humans fed homeostasis In normal animals
potassium
acutely.
potassium
acutely,
and
Hyperkalemia
dietary
is due to
excess.
i.
a high-potassium diet by enhancing renal potassium excretion (77,78). In addition, there is conflicting experimental evidence on the effect of mmeralocorticolds on extrarenal potassium disposal (2). Sugarman and Brown (79) studIed the effect of chronic mineralocortlcold administration on the dis-
albuterol has an additive effect. Hyperkalemia may be due to dietary excess, but fasting and $3-blockers are also important factors.
of Severe Hyperkalemia
Exercise
Recovery
bolus. May be repeated every 5 mm, if electrocardiographic appearance does not improve.
2. Regular insulin, bolus, followed 10 U + 50 ml of 50% dextrose, by 10% dextrose 0 50 mL/mln as iv until
0.6
0.5
10 to 20 mg, nebulized
over 10 bath.
against
a low potassium
0.4
0.3
Ut
0.2
*
*
0.1
of Hyperkalemia potassium restriction, 40 to 50 mmoi/day or 1.5 to 2.0 g/d. 2. Avoidance of nonselective /3-blockers. If 13-blockers are clinically indicated, use /3-1-selective blockers, e.g., atenolol or metoprolol. 3. During prolonged fasting in diabetic dialysis patients, infuse: 10% dextrose + 10 U of regular insulin/I 0 50
1. Dietary mi/h. During prolonged fasting in nondiabetic
0.0
dialysis
patients,
-0.1
0 50 mL/h.
-0.2
an
acute
potassium
load
in
The the
prior increase
exogenous
deoxycorticosterone
administration potassium
the
hemodialysis of the
for 60 h
mineralocorticoid
-0.3
acetate
in
plasma
after
an
20
30
Time,
40
minutes
50
60
70
acute tration
potassium of the
load. aldosterone
Conversely, antagonist
prior adminisspironolactone
Figure 6. Time course of change in plasma potassium concentration in dialysis subjects during exercise alone (open circles), exercise plus propranolol (closed circles), and exercise plus metoprolol (closed triangles). All values represent mean SE. P < 0.05 versus control study. P < 0.05 versus
metoprolol study. Reproduced with permission from Ref. 75.
augmented the hyperkalemic response to the potassium load. These intriguing observations suggest that exogenous mineralocorticoids may be a useful modality for the prevention of hyperkalemia in hemodialysis patients. In summary, clinical investigations performed In the past few years have enhanced our understanding of
1140
Volume
Number
4-
1995
Alion
the
mechanisms
of hyperkalemia
the guidelines of hyperkalemia for the
in ESRD
acute
patients.
and of
16.
As a result, prevention
treatment
in hemodlalysis patients to be revised (Tables 1 and 2). The utility calcium and insulin for acute hyperkalewith electrocardiographic unchallenged. In contrast, abnormalithe efficacy
Allon
M, Copkney
C: Albuterol
is normal in uremic and 1984;246:El74-E180. and insulin for treatment patients. Kidney Int S. Gnadinger M: Effect
of various
of 17.
therapeutic
P, Shaw approaches
on plasma
potassium
intravenous perkalemia
Albuterol,
bicarbonate for the treatment of hyis not supported by prospective studies. in either intravenous or nebulized form, to be a useful adjunct to the potassiumaction of intravenous insulin. Finally, dietary potassium restriction remains an
measure for the prevention of hyperkale-
18.
19.
mia, we have become more aware of nondietary contributing to hyperkalemia, including fasting and nonselective /3-blockers.
factors prolonged
20. 21.
ACKNOWLEDGMENTS
The author individuals
patients: Copkney, gratefully
to
Nancy
his
acknowledges Investigations
Linda
Shanklin.
and
Robert
Dunlay.
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. 1995