Principles of Dialysis and Dialysis of Drugs
JOHN F. MAHER, M.D.
Farmington, Connecticut
From the Division of Nephrology, Department of
Medicine, University of Connecticut Health Center,
Farmington, Connecticut. This study was sup-
ported in part by NIH Contract AM 5 2220 from the
Artificial Kidney-Chronic Uremia Program, Na-
tional Institute of Arthritis, Metabolism and Di-
gestive Diseases, Bethesda, Maryland. Requests
for reprints should be addressed to Dr. John F.
Maher, Division of Nephrology, Department of
Medicine, University of Connecticut Health Center,
Farmington, Connecticut 06032.
Consideration of the interactions of drugs and dialysis must include
an understanding of the mechanisms of transport during dialysis,
i.e., diffusion, ultrafiltration and membrane-protein binding effects.
Clearance is a function of molecular size, blood and dialysate flow,
membrane area and permeability, and dialyzer support geometry.
Protein binding and hematocrit decrease the in vivo clearances in
comparison to those measured in vitro with aqueous solutions. The
effect on the serum half-life is also determined by the distribution
space and clearance by other routes. Other factors such as meta-
bolic alterations of dialysis can affect pharmacologic activity, and
the clinical response is the end product of many determinants. Nu-
merous drugs are effectively removed by hemodialysis or at a slower
rate by peritoneal dialysis, which occasionally allows considerable
influx. The influence of intestinal contents on elimination rates by
peritoneal dialysis is unknown. Peritoneal dialysis can be influenced
considerably by vasoactive drugs.
The development of dialysis as a therapeutic reality has created a new
area of clinical pharmacology. The interactions of drugs and dialysis
include (1) depletion of therapeutic concentrations when dialysis is
undertaken for such other purposes as therapy of renal failure, (2)
therapeutic removal of drug excess by dialysis, (3) the effects of di-
alysis-induced metabolic alterations on drug actions and (4) the effect
of drugs on dialysis kinetics.
Solute removal by dialysis has numerous determinants [ 11. Dialysis,
as employed clinically, involves the juxtaposition of a semipermeable
membrane between a flowing stream of blood and an appropriate
rinsing solution. Resistance to movement of a given solute is a function
of the sum of the resistance to diffusion through the blood, the mem-
brane and the dialysate. Resistance to diffusion through each layer
is a function of solute size. The slope of the increase in resistance with
increased size is greatest for the membrane and least for an aqueous
dialysate [2]. As the thickness of each layer also determines the re-
sistance, the reciprocal of which is.the over-all permeability of the
dialyzer, it may be calculated as
Permeability (HO A) = k + -d-, -I- &
and expressed in units of length per time, customarily centimeters per
second (cm set-‘). In practice, the efficiency of a hemodialyzer for
April 1977 The American Journal of Medicine Volume 62 475
PRINCIPLES OF DIALYSIS AND DIALYSIS OF DRUGS-MAHER
removal of a given solute is expressed as dialysance
in milliliters per minute by the formula of Wolf et al. [3]
or a derivative thereof,
B, - B Do - Di
DzQ~~=QD-
i - Di Bi - Di
where Qe and Qo are flow rates of blood and dialysate,
respectively, Bi and B, are blood concentrations en-
tering and leaving the dialyzer, and Di and D, are the
comparable dialysate concentrations. Dialysance
rectifies the value to the actual diffusion gradient,
whereas by ignoring the dialysate concentration the
formula expresses a clearance. When the dialysate
concentration of a given solute is zero, the dialysance
and clearance are equal. At other times, dialysance
should be used as a measure of dialyzer performance
(assuming an infinitely fast dialysate flow or infinitely
high volume) and clearance should be used to assess
the effect on the patient under operating conditions. The
transmembrane diffusive transport is also affected by
the actual concentrations on the two surfaces of the
membrane. Accordingly, membrane support geometry,
and stagnant surface pools affect performance but are
not measured variables in the formula [4]. For solutes
of small size, the high diffusivity results in an important
decrease in concentration gradients across the mem-
brane. Clearances, therefore, increase considerably
as the flow rate of blood and/or dialysate is increased.
Under the usual operating conditions, the removal rate
of such solutes is predominantly flow limited. For larger
solutes, the rate of diffusion is less, concentration
gradients across the membrane remain high, and in-
creasing flow rates have little effect on clearances.
Such solute removal is predominantly limited by
membrane area X permeability. As a corollary to this
concept, Babb and colleagues [E] have advanced the
hypothesis that in dialyzed uremic patients inadequate
membrane area, permeability and/or duration of dialysis
lead to the accumulation of metabolites of relatively
large size that cause such morbidity as neuropathy.
Among the potential flaws in this hypothesis, we pointed
out recently that in our experience uremic patients are
also exposed to an average of five drugs of relatively
larger size, i.e., above 300 daltons, which might also
accumulate despite dialysis that is adequate for removal
of small solutes [4].
In addition to diffusive transport, solutes are removed
during dialysis by bulk flow in association with ultrafil-
tration, induced by hydrostatic and/or osmotic gradients.
Solute removal by ultrafiltration is not characterized by
discrimination according to molecular size until the
permeability limitation of the membrane is reached.
Although in a purely diffusive transport system the ratio
of the removal of a given large solute to a given small
476 April 1977 The American Journal of Medicine Volume 62
solute is an index of permeability, increasing ultrafil-
tration increases the removal of larger solutes to such
an extent as to increase the ratio and change the ap-
parent permeability [7]. Ultrafiltration may be associ-
ated with a decrease in diffusive permeability, however,
by widening the blood channel, lessening the membrane
area by impingement on the supporting mesh and
creating stagnant pools of dialysate adjacent to the
membrane [8,9]. Consequently, clearance data ob-
tained from one dialyzer under a given set of operating
conditions will apply only grossly to others with different
surface areas, flow geometry, transmembrane pressure
or membrane permeability.
For completeness, the third recognized type of dia-
lyzer transport involves adherence of a solute, such as
a trace metal, to the dialyzer membrane and removal
from the membrane by preferential binding by plasma
proteins [ 10,111. This mechanism allows for the influx
of solutes against an aqueous gradient, but it has not
been shown to apply to such organic compounds as
drugs. Nevertheless, protein binding of drugs may result
in a virtual unidirectional transport across the membrane
into the patient.
The in vitro measurement of dialysance or clearance
often translates poorly into the transport characteristics
during clinical dialysis. There has been insufficient
standardization of test methods for dialysance [ 121.
Plasma concentrations have been assumed to be rep-
resentative of whole blood concentrations, and blood
flow rates have been used on the assumption that blood
represents the volume from which the solute diffuses
to the dialysate. Figure 1 shows graphically the potential
effects of protein binding and hematocrit on clearance
in relation to values obtained in vitro with aqueous so-
lutions. As the fraction bound increases, clearance
decreases assuming that the bond is not highly labile.
A higher protein concentration also decreases the
fraction of plasma that is water and, by increasing vis-
cosity, will, at a given flow rate, increase hydrostatic
pressure and thus the ultrafiltration rate, or at a given
inflow pressure, will decrease blood flow rate. As the
hematocrit value increases, the flow rate of plasma
decreases at any given blood flow rate. Even for solutes
that are highly concentrated in cells, our data show that
during passage through a dialyzer, solute removal is
virtually exclusively from plasma [ 131. The rapidity of
intercompartmental transfer for most drugs is un-
known.
For solutes that are protein boynd, the binding may
be highly dependent on plasma protein concentrations
and solute concentrations. Although some highly bound
solutes do not saturate binding sites at physiologic or
pharmacologic concentrations, others demonstrate a
marked increase in the ultrafilterable fraction as plasma
 PRINCIPLES OF DIALYSIS AND DIALYSIS OF DRUGS-MAHER

Clearance
Bokd (PI
asma

Aqueous Plasma BI ood

Figure 1. Effect of protein binding and hematocrit value on dialyzer solute

clearance. In comparison to aqueous in vitro clearances, the clearance during
clinical dialysis decreases as a function of protein binding and hematocrit.

solute concentrations increase. Accordingly, we
demonstrated a progressive increase in iodide di-
alysance as iodide concentrations were increased [8].
This phenomenon can increase the value of therapeutic
dialysis for excesses of drugs that have saturable pro-
tein binding. We have correlated, inversely, the in vitro
dialysance of barbiturates with the extent of protein
binding, a relationship that invalidates a simple corre-
lation of clearance with solute size for these drugs [6].
Whether dialysance and protein binding vary as barbi-
turate concentrations vary is unknown. We have de-
termined recently that digoxin clearance by peritoneal
dialysis when corrected to plasma water concentration,
eliminating the influence of binding, ranges from 4.0 to
9.0 ml/min with a digoxin clearance to urea clearance
ratio of 0.30 to 0.45, appropriate for this molecular
size.
Given these problems in data interpretation, we can
consider the available information on the removal of
drugs by dialysis. This subject has undergone several
encyclopedic reviews [ 141. Dialyzer clearances above
80 ml/min may be achieved for several exogenous
solutes including bromide, long-acting barbiturates,
glutethimide, meprobamate, methyprylon, methanol,
ethanol, salicylates, lithium and thiocyanate. For some
solutes, higher clearances are achieved by direct he-
moperfusion of charcoal or resin columns [ 15,161.
As a general guide, those solutes that are normally
excreted by glomerular filtration will have high dialyzer
clearances. The renal clearance interposes tubular
transport, however, after ultrafiltration and does not
necessarily correlate with dialyzer clearance. For ex-
ample, the dialyzer slowly clears phenosulfonphthalein
which the tubule actively secretes, but very rapidly
clears bromide which the tubule reabsorbs almost
completely.
The dialyzer clearance must be considered in relation
to the total body clearance in order to predict the effect
on the biologic half-life of the drug. This may be ex-
pressed as
KV
T l/2 = -
R
where T1,2 is the half-life of a solute in minutes, K is a
constant, 0.693, V is the volume of distribution and R
is the elimination rate. When V is constant, a change
in R causes a reciprocal change in TI12, e.g., doubling
the elimination rate decreases the half-life by 50 per
cent. Thus, despite comparable dialyzer clearances,
hemodialysis affects considerably the half-life of the
slowly metabolized alcohol, methanol, but changes the
declining slope of plasma concentration of the rapidly
metabolized alcohol, ethanol, only slightly [ 171. By
contrast, under the physiologic circumstances en-
countered, some solutes are so slowly eliminated, for
example mercury, from the anuric patient, that a low
clearance by dialysis adds considerably to the removal

April 1977 The American Journal of Medicine Volume 62 477

PRINCIPLES OF DIALYSIS AND DIALYSIS OF DRUGS-MAHER
TABLE I Drug Intoxications Most Responsive
Clinically to Dialysis
Salicylates
Bromide
Thiocyanate
Barbiturates
Glutethimide
Ethchlorvynol
Meprobamate
Methyprylon
Methaqualone
Diphenylhydantoin
Lithium
Aminoglycosides
rate and thus decreases the half-life considerably
[181.
In relating dialyzer clearance to the physiologic
elimination rate, the effect of the drug itself on its own
elimination rate must be considered. One should not
compare the half-life during shock and dialysis with the
half-life during health and exposure to a low drug con-
centration. In studying glutethimide intoxication, we
determined that the plasma half-life increased with
shock and also increased independent of blood pressure
as the plasma concentration is increased, consistent
with a rate limited metabolic degradation [ 191. Ac-
cordingly, dialysis adds little to the relatively rapid re-
moval rate at low plasma concentrations, but since di-
alyzer clearance, unlike metabolic clearance, is not
concentration dependent, it adds considerably to the
removal rate at high concentrations.
Dialyzer clearance must also be related to the
clearance achieved by other therapeutic modalities. In
the patient who has severe intoxication with short-acting
barbiturates little gain may be achieved by forced di-
uresis, and the gain in removal rate achieved by adding
dialysis may be considerable. This contrasts with pa-
tients who have mild or moderate intoxication with
long-acting barbiturates who respond to forced diuresis.
Under this circumstance, the half-life may be sufficiently
brief that added removal by dialysis is not required. In-
deed, the response of bromide poisoning to forced di-
uresis with saline solution is often sufficient to decrease
the half-life to less than 6 hours and although higher
clearances are achieved by hemodialysis, the removal
rate from plasma may exceed the equilibration rate with
such extravascular bromide as that found in cerebro-
spinal fluid [ 19,201.
The distribution volume of a solute is a determinant
of the fraction removed by dialysis at any given clear-
ance. For solutes such as propoxyphene, glutethimide
and digoxin, the distribution space is very large due to
such factors as a high lipid partition coefficient or tissue
478 April 1977 The American Journal of Yedlclne Volume 62
binding. Although the dialyzer clearance may be high,
the low fraction in plasma means that only a small
quantity is presented to the dialysis membrane. Unless
equilibration with plasma is rapid, it is fallacious to
expect that enhanced removal by using lipid or protein
in dialysate or by charcoal or resin hemoperfusion will
materially change the removal from tissue reservoirs.
If equilibration keeps pace with the removal rate, the
calculated volume of distribution will not change (using
either the formula: amount removed/delta plasma
concentration or elimination rate X half-life/the con-
stant, 0.693). When equilibration does not keep pace,
the plasma concentration will decrease rapidly during
the procedure suggesting therapeutic success, and an
inappropriately small distribution space will be esti-
mated. A secondary rebound increment in the plasma
concentration will occur.
Dialysis has been criticized as a therapeutic modality
for some intoxications because the fraction removed
is small relative to the dose ingested and, consequently,
presumably relative to the body burdens. The as-
sumption is made that the entire body burden of the drug
is pharmacologically active, even though it is recog-
nized that there are examples to the contrary, such as
thiopental [21]. Such reasoning would argue that
therapeutic removal of potassium expressed as a
fraction of total body potassium is low and could not be
of clinical significance in the management of hyper-
kalemia, contradicting the obvious clinical experi-
ence.
In the final analysis, therefore, the clinical effect of
dialytic removal of a drug, often difficult to quantify
precisely, is the important measure of significance.
Comparisons between mildly intoxicated patients
treated conservatively, and severely intoxicated patients
treated with dialysis seem meaningless. Similarly, an-
ecdotal successes require validation.
With these interpretative constraints, a listing of drug
intoxications in which dialysis seems most useful, at
least in selected patients, is given in Table I.
The clinical judgement to employ or withhold dialysis
in a given case of poisoning is, of course, an individual
one, only guided by clearance data. Guide lines for the
clinical application of dialysis have been presented
elsewhere [ 201. It should be emphasized that some
drugs and poisons, such as nitrogen, mustard or anti-
cholinesterase agents, act more rapidly than removal
could be accomplished. Despite a rapid elimination rate,
therefore, toxic damage does not reverse.
When patients undergo dialysis for therapy of renal
failure, depletion of drugs and of physiologic solutes
such as vitamins and amino acids may occur. At phar-
macologic rather than toxic concentrations, such drugs
are usually measured with less precision and often the

clinical end point is less distinct than are the clinical
signs of toxicity. Based on available data [22], however,
the drugs frequently used in patients with renal failure
and removed by dialysis sufficiently rapidly that sup-
plemental therapy may be required, are listed in Table
II. Whenever possible, serum concentrations should be
measured to guide replacement therapy.
Dialysis may profoundly affect the pharmacologic
activity of a drug even though it changes the serum
concentration only slightly. The most recognized and
studied example of this effect is the precipitation or
aggravation of digitalis intoxication as dialysis corrects
hyperkalemia, hyponatremia, hypocalcemia and aci-
demia. The effect of the metabolic alterations of dialysis
on the activity of other drugs is largely unknown.
Changes in pH, protein concentration, osmolality, urea
or glucose can influence pharmacologic activity. Fur-
ther, the diminution by dialysis of such lesions as uremic
gastritis can decrease the toxicity resulting from a given
excess of certain drugs.
In patients with renal failure toxicity may develop
from accumulation of metabolic loads that derive from
drugs. Examples are the potassium content of penicillin,
the magnesium, the calcium loads and the alkalosis
derived from antacids, the sodium of carbenicillin and
the nitrogen derived from ammonium chloride or the
antianabolic effects of adrenal steroids or tetracycline.
Acidosis may result from a variety of drugs such as
ethanol, paraldehyde, nitrofurantoin, phenformin, iso-
niazid, carbenicillin or methenamine mandelate. Be-
cause of exaggerated metabolic abnormalities, as may
occur with these drugs, some patients may require di-
alysis earlier than otherwise.
The interaction of drugs and peritoneal dialysis in-
volve special considerations. firstly, it has been as-
sumed that the composition of the body fluids with which
peritoneal dialysate equilibrates is identical to that of
peripheral plasma. Based on our recent finding (Figure
2) of calculated peritoneal clearances of fatty acids
exceeding urea clearance and occasionally in excess
of dialysate flow rate, we have questioned whether the
denominator in this equation is equal to peripheral
plasma. Pending further study, we are considering the
possibilities that dialysate equilibrates directly with in-
terstitial fluid of high fatty acid content or with capillary
plasma, the composition of which is influenced more
by gastrointestinal contents than is peripheral plasma.
Either of these possibilities would raise an alternative
explanation for the observed infrequency of peripheral
neuropathy in patients undergoing peritoneal dialysis,
i.e., rather than efficient removal of larger solutes, a
high removal rate of toxins of intestinal origin. Direct
equilibration of peritoneal dialysate with a compartment
influenced by intestinal contents could also contribute
April
PRINCIPLES OF DIALYSIS AND DIALYSIS OF DRUGS-MAHER
TABLE II Drugs Usually Requiring Supplemental
Dosage After Dialysis
Aminoglycosides:
Streptomycin, Kanamycin, Gentamycrn, Tobramycin
Cephalosporins:
Cephalothin, Cephalexin, Cephapirin, Cephazolin
Penicillins:
Penicillin, Ampicillin, Carbenicillin
Other antibiotics:
Sulfonamides, Chloramphenicol, Trimethoprim, Cycloserine,
Ethambutol, 5-Fluorocytosine
Vasoactive drugs:
Aminophylline, Methyldopa, Procainamide
Immunosuppressive - chemotherapeutic agents:
Methotrexate, 5Fluorouracil. Cyclophosphamide
Miscellaneous:
Salicylates, Phenobarbital
to increased efficiency of removal of ingested drugs that
have a high fraction of the body burden in the form of
an intestinal reservoir.
Drug additives are included in peritoneal dialysis
solutions much more often than in hemodialysis baths.
If there is no protein binding of the solute, the influx rate
should closely approximate the rate of efflux. As many
drugs are protein bound, however, the efflux clearance
will decrease as the fractional binding increases, and
influx clearance will be maximal as the aqueous gra-
dient across the peritoneal membrane remains high.
Clearance data in one direction should not be inter-
preted as necessarily applying to the other.
Peritoneal dialysis is also distinctive since unlike
hemodialysis, the blood supply traverses arterioles.
Accordingly, the capillary bed has a better blood film
geometry than has been achieved extracorporeally, and
the blood flow is influenced by vascular disease and is
responsive to vasoactive stimuli. We have shown that
with systemic vascular disease there is a decrease in
clearances affecting predominantly larger solutes, so
that the ratio of creatinine clearance to urea clearance
decreases [ 231. These findings are compatible with a
decrease in peritoneal permeability, an abnormality that
is partially reversed by intraperitoneally administered
isoproterenol [24] and that can be reproduced in dogs
by the administration of dopamine [25]. We have been
studying the effect of the intraperitoneal administration
of vasoactive drugs in unanesthetized lightly restrained
New Zealand white rabbits undergoing peritoneal dial-
ysis. The initial studies have demonstrated a significant
increase in peritoneal clearances with the use of iso-
proterenol or tolazoline, whereas aminophylline had no
measurable influence on peritoneal permeability (Figure
3). That the clearance ratio did not decrease is com-
patible with an increase in permeability as well as flow.
We have interpreted these findings as compatible with
1977 The American Journal of Medicine Volume62 479
 PRINCIPLES OF DIALYSIS AND DIALYSIS OF DRUGS-MAHER

EXCHANGE #3

UREA METHYL-LAURATE -MYRISIATE -PALMITATE -0LEATE -STEARATE

Figure 2. The peritoneal clearance of urea is compared to that of several fatty

acids clearedduring three dialyses in two patients, one with and one without vascular
disease.

0’
IO 20 30 40 So 60

DWELL TIME (Minutes )

Figure 3. The peritoneal clearance of urea in Rabbit 6 14 is shown. Mean clear-

ances decrease as intraperitoneal dwell is prolonged. The intraperitoneal admin-
istration of isoproterenol or tolazoline significantly (p < 0.0 1) increases urea
clearance whereas the administration of aminophylline does not change values
compared to control measurements.

400 April 1977 The American Journal of Medicine Volume 62


dilation of the capillary lumen with resultant stretching
of the wall causing decreased wall thickness and in-
creased permeability. The increase to clearance and
permeability values above normal suggest that va-
soactive drugs can be used not only to restore clear-
ances toward normal, but also in those with normal
vasculature to achieve supranormal values. Such
capillary dilation when secondary to increased venous
pressure may be a factor contributing to increased
capillary permeability and ascites formation in patients
with cirrhosis.
Drugs, therefore, interact with dialysis in numerous
ways. Although many drugs are retained in renal failure,
excessive concentrations are ordinarily prevented by
reduction in dosage. Normal predialysis concentrations
of many drugs are sharply reduced by dialysis. This
1. Gotch FA, Autian J, Colton CK, et al.: The Evaluation of He-
modialyzers. U.S. Public Health Service Publication No.
72-103, 1972.
Craig L: Proceedings of the Conference on Hemodialysis
(Connally NT Jr, ed), U.S. Health Service Publication No.
64-1349, 1964. p 16.
Wolf AV, Remp DG, Kiley JE, et al.: Artificial kidney function:
kinetics of hemodialysis. J Clin Invest 30: 1062, 1951.
Maher JF, Nolph KD: Resistance to diffusion in dialyzers. Clin
Nephrol 1: 333, 1973.
Babb AL, Popovich RP, Christopher TG, et al.: The genesis
of the square meter-hour hypothesis. Trans Am Sot Artif
Intern Organs 17: 81, 1971.
6. Maher JF: Selective dialysis for removal of large solutes: a
reappraisal. Kidney Int 7s: 361, 1975.
7. Nolph KD, Nothum RJ, Maher JF: Ultrafiltration: a mechanism
for removal of intermediate molecular weight substances
in coil dialyzers. Kidney Int 6: 55, 1974.
8. Maher JF, Schreiner GE, Marc-Aurele J: Methodologic prob-
lems associated with in vitro measurements of diilysance.
Trans Am Sot Artif Intern Organs 5: 120, 1959.
9. Husted FC. Nolph KD, Vitale F, et al.: Detrimental effect of
ultrafiltration on diffusion in coils. J Lab Clin Med 87: 435,
1976.
10. Maher JF, Freeman RB, Schmii G, et al.: Adherence of metals
to cellophane membranes and removal by whole blood. A
mechanism of solute transport during hemodialysis. Trans
Am Sot Artif Intern Organs 11: 99, 1965.
11 Maher JF, Montero G, Chieffo S: Tin-protein binding kinetics
in normal and uremic plasma and its effect on,dialysis
fluxes. Trans Am Sot Artif Intern Organs 22: 149, 1976.
12. Bass OE, Nolph KD. Maher JF: Dialysance and clearance
measurements during clinical dialysis-a plea for stan-
dardization. J Lab Clin Med 86: 378, 1975.
13. Nolph KD, Bass DE, Maher JF: Acute effects of hemodialysis
on removal of intracellular solutes. Trans Am Sot Artif In-
tern Organs 20: 622, 1974.
April 1977
PRINCIPLES OF DIALYSIS AND DIALYSIS OF DRUGS--MAHER
technic can also be used to increase the removal of
toxic concentrations of drugs. Alternatively, dialysis may
be a mechanism for removing metabolic loads asso-
ciated with or derived from drugs. Large molecular size,
high fractional protein binding or a large distribution
space can limit the decrease in plasma concentration
associated with dialysis. The metabolic alterations in-
duced by dialysis also may affect importantly the
pharmacologic activity of drugs. With peritoneal dialysis,
clearances may be affected by vasoactive drugs that
enhance or decrease blood flow and membrane per-
meability. The fluid compartment(s) with which perito-
neal dialysate equilibrates may be influenced by in-
testinal contents providing a route for the elimination
of ingested drugs before equilibration with body stores
is achieved.
14. Schreiner GE, Teehan BP: Dialysis of poisons and drugs-
annual review. Trans Am Sot Artif intern Organs 18: 563,
1972.
15. Nealon TF Jr, Sugerman H, Shea W, et al.: An extracorporeal
device to treat barbiturate poisoning. Use of anion ex-
change resins in dogs. JAMA 197: 118, 1966.
16. Chang TMS, Coffey JF, Lister C, et al.: Methaqualone, meth-
yprylon, and glutethimide clearance by the ACAC micro-
capsule artificial kidney. Trans Am Sot Artif Intern Organs
19: 87, 1973.
17. Marc Aurele J, Schreiner GE: The dialysance of ethanol and
methanol. A proposed method for the treatment of massive
intoxication by ethyl or methyl alcohol. J Clin Invest 39: 892.
1960.
18. Maher JF, Schreiner GE: The dialysis of mercury and mer-
cury-BAL complex. Clin Res 7: 298, 1959.
19. Schmitt GW, Maher JF, Schreiner GE: Ethacrynic acid en-
hanced bromuresis. A comparison with peritoneal and
hemodialysis. J Lab Clin Med 68: 913, 1966.
20. Schreiner GE: The role of hemodialysis (artificial kidney) in
acute poisoning. Arch Intern Med 102: 896, 1958.
21. Brodie BB, Bernstein E, Mark LC: The role of body fat in limiting
the duration of action of thiopental. J Pharmacol Exp Ther
105: 421, 1952.
22. Anderson RJ, Gambertoglio JG, Schrier RW: Fate of drugs in
renal failure, The Kidney (Brenner BM, Rector FC Jr, eds),
Philadelphia, W.B. Saunders Co., 1976.
23. Nolph KD, Stoltz M, Maher JF: Altered peritoneal permeability
in patients with systemic vasculitis. Ann Intern Med 75: 753.
1971.
24. Brown ST, Ahearn DJ, Nolph KD: Reduced peritoneal clear-
ances in scleroderma increased by intraperitoneal iso-
proterenol. Ann Intern Med 78: 891. 1973.
25. Gutman RA, Nixon WP, McRae RL, et al.: Effect of intraperi-
toneal and intravenous vasoactive amines on peritoneal
dialysis: study in anephric dogs. Trans Am Sot Artif Intern
Organs 22: 570, 1976.
The American Journal of Medicine Volume 62 461