Kidney International, Vol. 29 (1986), pp. 901—907

Heterogeneity of the cardiovascular response to hemofiltrationLEE W. HENDERSON

Department of Medicine, Veterans Administration Medical Center, San Diego, California; and Department of Medicine, University ofCalifornia, San Diego, La Jolla, California, USA

Heterogeneity of the cardiovascular response to hemofiltratlon.Twenty—one stable maintenance hemodialysis patients were studied ina crossover format with hemofiltration to determine whether the lowerincidence of symptomatic hypotension noted with hemofiltration couldbe correlated with changes in barorefiex function as tested using thecold pressor test and amyl nitrite inhalation study. Baroreflex functionremained abnormal and unchanged in all patients in the face of areduced incidence of symptomatic hypotension. Subdivision of thepatients into frequent (> 1 episode/treatment) and infrequent (< Iepisode/treatment) reactors during the hemodialysis control periodresulted in the infrequent reactors, showing a significant increase inepisodes of symptomatic hypotensionlhemofiltration treatment where asignificant reduction was noted with the frequent reactors. No clearcorrelation could be made between the incidence of symptomatichypotension and the pre- to post-treatment change in body temperature.The presence of pretreatment hypertension, another previously identi-fied correlate of symptomatic hypotension with hemodialysis, alsocould not be corroborated. Further, changes from baseline predialysisvalues in mean arterial pressure noted with hemofiltration could not becorrelated with a changed incidence of symptomatic hypotension. Weconclude that previously identified correlates of symptomatic hypoten-sion noted in the hemodialysis setting may be dissociated duringtreatment with hemofiltration and that there is a heterogeneous patientresponse to this treatment. These data suggest that there are additional,as yet undetermined, pathophysiologic events that underly the symp-tomatic hypotension of artificial kidney treatment.

A significant fall in blood pressure accompanied by a varietyof symptoms occurs in approximately 20 to 30% of all hemodi-alysis treatments in patients with stable end stage renal failure[1, 2, 3]. Hemofiltration for reasons yet to be explained isassociated with a lower incidence (approximately 10%) of thismorbid event [1, 3, 4]. Autonomic neuropathy is demonstrablypresent in upwards of 50% of patients with end stage renaldisease [5, 6] and has been correlated with both the occurrenceof symptomatic hypotension during hemodialysis and to hyper-tension between treatments [7]. Recent work suggests that a fallin body temperature induced by hemofiltration correlates withimproved cardiovascular stability during treatment [8].

The present work examines baroreflex arc function and bloodpressure as well as changes in body temperature and weight inpatients moving from maintenance hemodialysis to mainte-nance hemofiltration, to determine whether there is a correla-

Received for publication February 22, 1985,and in revised form July 23, 1985

© 1986 by the International Society of Nephrology

901

tion between the reduced incidence of symptomatic hypoten-sion, and these previously identified correlates.

Methods

Twenty-one patients (20 m, 1 1) with end stage renal failurebeing maintained on a Monday, Wednesday, Friday, four—hourhemodialysis schedule, using cellulosic membrane (cuprophanefor 17, cellophane for 4) dialyzers were selected for study. Theywere free of identifiable systemic disease, specifically: infec-tion, diabetes mellitus, lupus erythematosis, periarteritis andamyloidosis. All were taken from the hemodialysis unit of theVAMC San Diego and were considered to be stable mainte-nance dialysis patients. Informed consent was a requirement forparticipation in the study. The average time on dialysis was 24

7 mo. The mean age of the study group was 55 3 yrs (31 to71 year range). Six patients were normotensive and 15 hadhypertension, defined as a pretreatment mean arterial pressure> 105 mmHg, determined when the patient was considered tobe at or below his "dry weight." All antihypertensive medica-tion was discontinued two weeks prior to the start of the studyprotocol and was withheld for the duration of the study.

Hemodialysis was carried out using an acetate bath. Patientswere then switched to hemofiltration for twelve weeks usingreplacement solution that contained a higher acetate and so-dium concentration than that used for hemodialysis (Table 1).Hemofiltration was carried out with predilution using 0.55 MXP-50 hollow fiber polysulfone membrane (Grace Amicon D-30hemofilter, Amicon, Lexington, Massachusetts, USA). Fifty to70 liters of diluting fluid was used per treatment.

Seated blood pressure was obtained using an arm cuff by thenurse just prior to initiating treatment and hourly thereafter.Treatment for episodes of SH consisted of intravenously ad-ministered hypertonic saline (50 mEq in 12 cc) mannitol (25 g in25 cc) or isotonic saline (100 to 300 cc) singly or rarely incombination. During treatment, symptomatic hypotension wasconsidered to be present when the nurse treated the patient forsymptoms and/or the measured blood pressure was at or below100/70 mmHg or was 20/20 mmHg below the last hourly routinerecorded blood pressure. Beam balance body wts were ob-tained pre- and post-treatment.

The amyl nitrite inhalation study was conducted on the dayfollowing dialysis. Blood pressure was monitored using abrachial artery catheter and a pressure transducer (Hewlett-Packard Model 1280C, Elkhart, Indiana, USA) connected to atwo channel strip chart recorder (Hewlett-Packard 7702B).Lead V-2 of the EKG was simultaneously recorded at a paper

902 Henderson

Dialysis Bath Diluting Fluid

Sodium 133 140Potassium 2.0 2,0Calcium 3.5 3.5Magnesium 1.5 1.5Chloride 105 106Acetate 37 41Glucose 100 (mg%) 100 (mg%)

speed of 25 mm/sec. Barorefiex sensitivity obtained when bloodpressure was below baseline was evaluated by recording theincrease in heart rate in response to a fall in arterial pressureinduced by amyl nitrite inhalation [91. Changes in mean arterialpressure (MAP) and pulse interval were recorded continuouslyfollowing amyl nitrite inhalation. Baroreflex sensitivity wascalculated as the quotient of the induced pulse interval changein the EKG on the succeeding beat divided by the change inMAP on the preceding beat, utilizing cardiac cycles at baselineand during development of maximal amy! nitrite induced hypo-tension. Results are expressed as units of msec/mmHg. Thecold pressor test was conducted by having the subject place hishand (contralateral to the site of vascular access) in ice waterfor one minute during continuous monitoring of the EKG andintraarterial pressure. Both the change in R—R interval (msec)and maximum change in MAP were recorded. Temperature wasmeasured just before and at the conclusion of each artificialkidney treatment using a sublingual thermister (IVAC Model811).

Pretreatment levels in plasma were obtained for sodium,blood urea nitrogen and plasma dopamine B-hydroxylase(DBH) activity from the seated patient without tourniquetthrough the fistula needle between 7:45 and 8:00 a.m. prior toinitiating dialysis. The spectrophotometric method of Negatsuand Udenfried as previously reported by our group [10] wasused to measure DBH (International units/liter). Three mea-surements were performed serially: prior to each of threetreatments, at the conclusion of the dialysis study period, and atthe conclusion of hemofiltration. Values were averaged for eachpatient to obtain a single study period value for statisticalanalysis.

Paired and non-paired t tests were used as appropriate forcomparisons of the same patient with different treatment mo-dalities, or between different patient groups on the same mo-dality. Analysis of variance was used to determine the signifi-cance of differences in the monthly study periods for a giventreatment modality.

Results

Figure 1 plots the percent of treatments in which one or moreepisodes of symptomatic hypotension occurred withhemodialysis and hemofiltration in the group of 21 patientsstudied. While values for the first and second month (F-i 54

6%, F-2 = 44 6%, mean 1 suM) show lower values thanfor the 343 control observations on hemodialysis (58 8%),they do not achieve statistical significance at the P < .05 leveluntil the third month (F-3 = 34 6%). With the first month backon hemodialysis there is a prompt return to the control value

Number of treatments with SHx 100 in 21 patients

Number nf treatments

(Mean 1 SFM(

N 343 315 269 248 289 255 304

* Pc 0.05 vs. 0-0Study period

Fig. 1. Percent incidence of symptomatic hypotension (SH) in 21patients is shown. Control observations on hemodialysis (D-0) arecompared with three months of hemofiltration treatment (F-i, F-2,and again with three months of post hemofiltration hemodialysis (D-1,D-2, D-3). N represents the number of treatments observed in eachstudy period.

and this frequency is maintained until the end of the study.Examination of the number of episodes of symptomatic hypo-tension per study period (not shown), which takes into accountmultiple episodes of symptomatic hypotension during a singletreatment rather than the number of treatments, in which one ormore episodes of symptomatic hypotension occurred results insimilar findings, except that statistical significance is present inthe F-2 study period in additon to F-3.

Figure 2 divides the patient study group using the criterion ofhypertension. The six patients with MAP less than or equal to105 mmHg show an insignificant fall in episodes of symptomatichypotension per treatment on changing to hemofiltration. Thesame holds true for those with hypertension. The number ofstudy subjects (N 15) in the hypertensive group increases thestrength of this lack of significant difference considerably.

An alternative way of analyzing this data takes into accountthe clinical perception that certain patients are prone to havesymptomatic hypotension, whereas others appear to be resist-ant to this ill effect of treatment. Figure 3 divides the studypopulation on the basis of the number of episodes of sympto-matic hypotension per treatment during the control period onhemodialysis. Ten patients who, on average, had one or lessepisodes of symptomatic hypotension per hemodialysis treat-ment are shown as group A (0.48 0.1 episodes per treatment)to the left whereas the remaining 11 (Group B) with more thanone episode per treatment (2.1 0.2) appear in the bar graph to

Table 1. Comparative composition of the hemodialysis bath andhemofiltration diluting fluid in mEq/liter.

C0U,

a0a.00aS0aSaCaUaa-

70

50

40

30

20

10

00-0 F-i F-2 F-3 0-1 0-2 0-3

Cardiovascular response to hemofiltration 903

Average number of episodes of SH pertreatment (mean SEMI in two groups

selected by starting frequency

Average number of episodes of SHper treatment (mean 1 SEMI in

groups selected by MAP

NS

P < .02

NS

P < .005

HD HF HD HF

N=> 105

15

HD HF HD HF

a)Ea)a)

a)a0CO

Ca)

0a>(C

a)E0aEl>-CO

0CO

a)00COaw

0

MAP (mmHg( 105

6

Fig. 2. The number of episodes of SHfor each treatment is shown. Thestudy subjects are divided into those with hypertension (mean arterialpressure> 105 mmHg) and those who are normotensive. Hemodialysis(HD) is compared with hemofiltration (HF). N represents the number ofpatients in each group.

the right. Examining their response to hemofiltration shows thatfor the three months of this experimental therapy, Group A hada statistically significant increase in symptomatic hypotensionwith hemofiltration, whereas Group B showed a significantreduction in incidence.

Figure 4 plots episodes of symptomatic hypotension pertreatment for only the hypertensive patients. This group wasfurther subdivided into those who showed a statistically signif-icant fall in MAP when control observations on hemodialysiswere compared with the values obtained in the third month onhemoffitration, and those who showed either no change or anincrease in MAP over control values. Only the latter group (N= 5), who showed no change or a worsening of their hyperten-sion, had a significant improvement in their frequency ofsymptomatic hypotension per treatment.

Mean pre- to post-treatment sodium levels in the plasma forthe entire patient group were no different than control measure-ments (D-0 = 133 .6 to 130 .64 mEq/Liter) for the thirdmonth ofhemofiltration (F-3 = 134 .5 to 132 1.4 mEq/Liter)or in the third month of return to dialysis (D-3 = 132 .9 to 127

2.1 mEq/Liter). Table 2 compares the sodium and blood ureanitrogen concentration of the plasma in study Groups A and Bprior to treatment and shows the pre- to post-treatment changein concentration for these parameters obtained during thecontrol period on hemodialysis (D-0) and for the third month onhemofiltration (F-3). None of the differences between study

3

Ca)Ea)a)

a)aC0COCa)0a>-

a)a)E0aEl00)a)0COaw

0

GroupA GroupB(± 1) 1> 1)N= 10 11

Fig. 3. The number of episodes of SN for each treatment is shown. Thestudy subjects are divided into Group A and B according to whether theincidence of SH in the D-0 control period ws <I or >1. The incidenceof SH with HD is compared with HF.

Groups A and B achieved statistical significance. Actually thechange in both the concentrations of urea and sodium noted inthe D-0 control period for Group A (low incidence) were largerthan Group B, which is the reverse of what might be expectedif changes in plasma osmolality are to be correlated withsymptomatic hypotension. As expected, pretreatment valuesfor blood urea nitrogen were slightly higher for both studyGroups during the hemoffitration treatment period. Weight lossduring treatment for both study periods showed no differencebetween Groups A and B. As altered body content of sodiumcould be masked by parallel changes in body water, we exam-ined the relationship between total body water as reflected bybody wt and pretreatment MAP. A least squares regression ofpretreatment MAP on wt gain between treatment days wasperformed for the data pairs from the entire study population of21 patients and for the A and B subsets of the populationdiscussed above. Table 3 gives the regression parameters forthese lines and their statistical significances. The correlationcoefficient values are very low (0.13 to 0.10) suggesting the lackof any useful predictive relationship between these parametersfor a given treatment. The slopes for all three lines, however,are highly significantly different from zero. The statisticalstrength of the difference in slopes from zero stems from thelarge number of data pairs (N) available for analysis. Theintercepts of the lines, that is, MAP with no gain in weightbetween treatments, show group A (109 mmHg) to be verysignificantly (P < 0.001) higher than group B (105 mmHg).

Table 4 shows temperature change with treatment for 17 of

904 Henderson

those who did not, failed to reveal any statistical differences.Not shown are the results of the cold pressor test as all valueswere within normal limits both on hemodialysis and hemofiltra-tion. This finding is comparable to prior studies by others [5, 7]in patients on hemodialysis,

Discussion

The present study tries to correlate the improved hemody-namic stability noted during hemofiltration treatment with pre-viously identified correlates of stability noted on studying theresponse to hemodialysis alone; that is, hypertension afferentlimb barorefiex arc neuropathy and increase in body tempera-ture [7, 8]. In examining the entire group, the mean arterialpressure at dry weight, Table 3, was higher for those who hadfewer episodes of symptomatic hypotension (Group A) than forthose who had the higher frequency (Group B). When selectingpatients by the presence or absence of hypertension duringmaintenance hemodialysis, we were not only unable to show aparallel difference in the incidence of symptomatic hypotensionbut were unable to correlate its change in incidence withchanges in pretreatment MAP. Further, the normotensive andhypertensive patients showed an insignificant reduction insymptomatic hypotension of equivalent degree (Fig. 3) and ifthe study subject number had been marterially larger we mightwell have been able to demonstrate a significant fall in bothgroups. With reference to Figure 4, further analysis of only thepatients with hypertension showed that those with a fall in meanarterial pressure, when mean values for the D-0 control periodwere contrasted with the third month on hemofiltration, showedthe same incidence of symptomatic hypotension when movingto hemofiltration. Even more at odds with previous work [5, 6,7] is the observation in those patients who showed no change oran increase in mean arterial pressure that there was a significantreduction in the incidence of symptomatic hypotension onmoving to hemofiltration (Fig. 4). Lastly, with respect to thecorrelation between the presence of hypertension and a highfrequency of symptomatic hypotension, is our observation thatmean arterial pressure in those patients showing the higherfrequency, Group B is lower than in Group A with the lowincidence. This finding is at odds with the work of Lilley et al inwhich a positive not an inverse correlation was made in a verysimilar patient population [7].

We were unable to document any change in the amyl nitriteinhalation test with hemofiltration. Others have failed to corre-late the incidence of symptomatic hypotension with baroreflexarc dysfunction, however this latter work relied on valsalvamaneuver and venoconstrictor response rather than amylnitrite—induced hypotension as the test modality [12]. It shouldbe noted that the amyl nitrite inhalation study tests thecardioregulatory element of the baro:eflex arc which has avasoregulatory component in addition [13]. We would not havebeen able to identify a selective improvement of vasoregulationwith the present study protocol except as it might be reflected inthe lowering of MAP with hemofiltration. However, the corre-lation in our study of a fall in incidence of symptomatichypotension with no change or an increase in MAP on switchingto hemofiltration, points away from a direct role of the auto-nomic nervous system in this fall in incidence of symptomatichypotension. The lack of change noted in plasma dopamineB-hydroxylase also supports this lack of correlation. Our data

Average number of episodes of SRper treatment (Mean 1 SEM( inpatients with MAP 105 mmHg

NS P = 0.05

RD HF RD HF

3

Ca,Ea,a)

a)a'0a)0a>,C)

Co

E0aU)

0U)a)'C0a)aw

0

MAP Fall No change or increase

N 9 6

Fig. 4. The number of episodes of SHfor each treatment is shown. Onlythose study subjects with MAP> 105 mmHg in the D-0 control periodwere selected (N = 15). These subjects were further subdividedaccording to whether MAP fell significantly (P C 0.05) or not with HF.

the 21 patients in which temperature recordings were completeon all treatments with hemodialysis and hemofiltration. Therewas a significant rise in temperature with both procedures, andthat noted for hemodialysis was significantly more than thatwith hemofiltration. Figure 5 shows the temperature changewith treatment for study groups A and B. Changes in Group Awere no different than those for Group B, and neither showed asignificant difference in pre- to post-temperature on movingfrom hemodialysis to hemofiltration.

Dopamine B-hydroxylase values (mean I snM) drawnpretreatment for all patients showed no significant differencesbetween the control value on dialysis (D-0 = 37 7 lu) and thatafter three months on hemofiltration (F-3 = 33 S Ju) or thatfollowing return to three months of dialysis (D-3 = 36 6 lu)plasma.

Not all patients consented to undergo autonomic nervoussystem testing and hence only 13 complete studies are availablefor analysis. Amyl nitrite inhalation studies and cold pressortests were conducted on three of the normotensive patients and10 of those with hypertension. Studies were performed at theconclusion of the control study month on hemodialysis andrepeated at the conclusion of the third month on hemofiltration.Table 5 shows the results for the amyl nitrite test. All values ofthe amyl nitrite inhalation test were markedly abnormal (<5msec/mmHg) when compared with non-uremic control subjects(17.4 4.1 msec/mmHg) [11] and remained so following threemonths of treatment with hemofiltration. Dividing the popula-tion into Group A vs. Group B (not shown), or normotensivevs. hypertensive groups, or those who showed a fall in MAP vs.

Cardiovascular response to hemofiltration 905

Table 2. Sodium, BUN and body weight values for study groups A and B.

Treatmentperiod

Group A Group B

BUN,mg/dliter

Sodium,mEqlliter

Weight,kg

BUN,mg/dliter

Sodium,mEqlliter

Weight,kg

D-0PrePre-Post

F-3PrePre-Post

91 1147 7

96 837 6

133 1.33.2 .98

132 1.50.52 .74

75.9 1.91.84 .3

73.3 2.72.70 .3

80 339 394 840 6

134 2.42.4 1.1

132 2.11.5 1.3

74.74 2.12.3 .2

73.6 2.42.30 .3

No statistically significant differences are noted either between group A and B values or for those within a study group between the D-0 and F-3study periods.

Intercept,Group Slope 1 SEM mmHg r P Slope N

All Patients 1.54 31 107 .12 <0.0001 1850A 1.7 0.4 109* .13 <0.0001 938B 1.3 0.4 105* .10 0.0035 912

* P < 0.0001.

Hemodialysis (Pre vs. Post) +0.99 0.72 N = 17 P < 0.001Hemofiltration (Pre vs. Post) +0.36 0.58 N = 17 P = 0.02

does not, however, remove autonomic neuropathy from con-sideration as an underlying abnormality in the end stage renalfailure patient that may contribute to vascular instability duringvariations in intravascular volume. The lack of good qualitylinear correlation between MAP and intertreatment wt gain is ofinterest in this regard. One must argue that fluid wt gainbetween treatments must either not be reflective of changes inplasma volume or that plasma volume and MAP do not corre-late well in this population. Previous work by ourselves andothers indicates that while plasma volume itself shows a poorcorrelation with MAP in the chronic uremic patient, the ratio ofplasma volume to interstitial volume correlates very well indeed[14, 15].

Maggiore et al [81 have presented evidence that routinemaintenance hemofiltration is associated with lower core bodytemperature than hemodialysis, and that when experimentalmanipulation reverses this temperature difference that hemody-namic instability during treatment reverses in parallel withfewer episodes of symptomatic hypotension for bothhemodialysis and hemofiltration. Our data does not contest thathemodynamic stability may be improved by cooling of thepatient, but rather disputes that temperature is the causativeforce that links fewer episodes of symptomatic hypotensionwith hemofiltration when contrasted with dialysis. Recent workfrom this group points up a reduction in complement activationthat occurs with reduced blood temperature in the extracorpo-

IAI IBI ____________A' IB'I1

8 9 8 9

Patient group (N)

RR in MilliseMean

c/MAP mmHg,1 SEM

HD Post-HF

Normotensive (3)Hypertensive

MAP, fall (5)MAP, no change or increase (5)

3.50

2.162.07

.65

.45

.62

4.11 1.83

1.53 .182.63 1.3

No significant differences are present.

real circuit [16]. We and others have shown complementactivation to be strongly present with exposure of blood tocuprophane membrane either in vivo or in vitro [17—201. Whileclear proof of a causative link between symptomatic hypoten-sion and complement activation is at present lacking, the studyof Hakim et al [21] showing a correlation between C3a levelsand signs and symptoms occurring during dialysis, as well as

Table 3. Regression line parameters.

MAP on weight gain, kgPOST- PR E

TEMP

Temperature response toTreatment for groups A(1)

and 8(>1)

NS NS

Table 4. Temperature change with treatment in degrees farenheit,Mean 1 SEM.

1.0 —

°F 0

n

—1.0

The difference in temperature rise between hemofiltration andhemodialysis is significant (P = 0.03).

T

Hemodialysis Hemofiltration

Treatment

Fig. 5. The change in temperature is shown in degrees farenheit (F)forstudy subject groups A and B during hemodialysis in the left panel. Theresults for the same study subjects are shown in the right panel (A', B')during hemofiltration.

Table 5. Amyl nitrite inhalation study.

906 Henderson

recent work [221 on the lower incidence of symptomatic hypo-tension with reused cuprophane dialyzers (saline rinse formal-dehyde storage protocol), taken in context with the report oflower complement activation in these reused dialyzers [181, issupportive of such a link. Studies of complement activation byourselves and others point up that the polysulfone membraneused for hemofiltration in this study does not show significantcomplement activation [23, 24]. Further investigation will benecessary to determine if this difference in membrane proper-ties underlies the lower incidence of symptomatic hypotensionin this study, or for that matter, in other studies comparingsymptoms and signs between hemodialysis and hemofiltration.The identification that one subset of our study population showsan increase in symptomatic hypotension on moving topolysulfone membrane will have to be taken into account beforeaccepting this explanation.

The lack of difference in wt lost during treatment betweenpatients on hemodialysis and hemofiltration and, in particular,where the patients are broken out by A and B study groups,points away from a correlation between symptomatic hypoten-sion and the amount of ultrafiltrate removed per treatment. Adifference in distribution between body spaces of this net loss oftotal body water for hemofiltration and hemodialysis mighthowever be explanatory [151. The difference in composition ofthe dialysis bath and diluting fluid bears comment. The netosmolar flux rate is an important secondary determinant ofvascular volume in that vascular refilling rate is a function ofoncotic, osmotic, and hydrostatic transmembrane pressures atthe microvascular level [25, 26]. Sodium in the substitution fluid(140 mEq/liter) of the present experiment was higher than thatused in dialysate (133 mEq/Liter). Sodium concentration of theplasma water at the end of treatment then might be expected tobe higher with hemofiltration than with hemodialysis. That it isnot suggests greater recruitment of sodium—free water from theintracellular space. Such an increase in extracellular watermight be expected to improve cardiovascular stability. Thatstudy Group A showed an increase in symptomatic hypotensionwith hemofiltration points away from the difference in netosmolar flux as causative in the reduced incidence of sympto-matic hypotension noted with hemofiltration. In addition, workby Shaldon et al [27] points away from net sodium balance asetiologic in this event. The use of acetate for both treatmentmodalities, and its direct delivery into the blood path withhemofiltration, points away from the cardiodepressant/vaso-dilatory properties of this agent as explanatory of any differ-ences noted between the two techniques.

In conclusion, the present experiments do not support theprevious empirical correlation put forward by Lilley et al [7]between cardiovascular instability during hemodialysis treat-ment (as manifest by the incidence of symptomatic hypoten-sion) and hypertension. Furthermore, the incidence of sympto-matic hypotension could be dissociated from afferent limbbaroreflex arc neuropathy, net body temperature change, andalterations in net osmolar flux when treatment with hemofiltra-tion was introduced. It is not readily apparent as to why ourresults differ from Lilley et al [7], except as selection criteria forthe patients utilized were different and patient populations forboth our study (N = 21) and that of Lilley et al (N = 10) weresmall. The degree of improvement in the amyl nitrite inhalationstudy noted by Lilley et al was from a value of 1.2 0.6 to 5.1

1.6 msec/minHg. It should be noted that while these numbersshow statistical significance, the clinical meaning of the differ-ence between them has yet to be established when normalvalues in the nonuremic control population are 17.4 4mmsec/mmHg. Lastly, while temperature variation with treat-ment in our work did not correlate in the manner described byMaggiore et a! [8] with the incidence of symptomatic hypoten-sion, the study designs were sufficiently different to preventdetailed comparison. As previously noted, correlation betweentemperature elevation and clinical symptoms will require differ-entiation between net calorie balance across the extracorporealblood circuit and other events that may result in alterations inbody temperature [281.

AcknowledgmentsThis work was funded, in part, through the Veterans Administration.

The author acknowledges the technical assistance of Dawn Otsuka, thestatistical assistance of J. K. Leypoldt and the secretarial assistance ofHelen Lojwaniuk.

Reprint requests to Dr. L. W. Henderson, VA Medical Center, 3350La Jolla Village Drive, San Diego, California 92161, USA.

References

1. QUELLHORST EA, SCHUENEMANN B, HILDREBRAND U: Morbidityand mortality in long term hemofiltration. asoio J 6:185—191, 1983

2. KANT KS, POLLAK YE, KATI-JEY M, GOETZ 1), BERLIN R: Multipleuse of dialyzers: Safety and efficacy. Kidney mt 19:728—738, 1981

3. HENDERSON LW: (Editorial) Symptomatic hypotension duringhemodialysis. Kidney mt 17(5):57l—576, 1980

4. BALDAMUS CA: Clinical value and technical feasibility of long termhemofiltration. asaio J 6:192—196, 1983

5. KERSH ES, KRONFIELD SJ, UNGER A, POPPER RW, CANTOR 5,KOHN K: Autonomic insufficiency in uremia as a cause of hemo-dialysis—induced hypotension. N Engl J Med 290:650—653, 1974

6. CAMPESE VM, ROMOFF MS, LEVITAN D, LANE K, MASSRY SG:Mechanisms of autonomic nervous system dysfunction in uremia.Kidney mt 20:246—253, 1981

7. LILLY J, GOLDEN J, STONE R: Adrenergic regulation of bloodpressure in chronic renal failure. J Clin Invest 57:1190—1200, 1976

8. MAGGIORE Q, PIZZARELLI F, SISCA S, ZOCCALI C, PARLONGO S,NicoLo F, CREAZZO G: Blood temperature and vascular stabilityduring hemodialysis and hemoffitration. Trans Am Soc Art if InternOrgans 28:523—527, 1982

9. THOMSON PD, MELMEN KL: Clinical assessment of autonomicfunction. Anesthesiology 29:724—731, 1968

10. FRIGON RP, O'CONNOR DT, LEVINE GL: Human dopaminebetahydroxylase. Molec Pharmacol 19:444—450, 1981

11. LEVY SB, LILLEY JJ, STONE RA: Baroreflex function in uremic andhypertensive man. Am J Med Sci 276:57—66, 1978

12. NIE5 AS, ROBERTSON D, STONE WJ: Hemodialysis hypotension isnot the result of uremic peripheral autonomic neuropathy. J LabClin Med 94:395—402, 1979

13. CHAIGNON M, CHEN W, TARAZI RC, Bivo EL, NAKAMOTO S:Affect of hemodialysis on blood volume distribution and cardiacoutput. Hypertension 3:327—332, 1981

14. HENDERSON LW: Possible role of the autonomic nervous system inblood pressure with hemofiltration. Proc 1st Geissen Symposiumon Hemodiafiltration, pp. 119—136, 1981

15. KINET J, SOYEUR D, BALLAND N, SAINT—REMY M, COLLIGNON P,G01WON J: Hemodynamic study of hypotension during hemodial-ysis. Kidney mt 21:868—876, 1982

16. MAGGIORE Q, ENIA G, CATALANO C, MISAFARI V, MUNDO A,CREAZZO G, ZACCURI F: Anaphylatoxin release and leukopeniaduring cool hemodialysis. (abstract) 17th Ann Mtg ASN, p. 69A,1984

17. CHENOWETH DE, CHEUNG AK, HENDERSON LW: Anaphylatoxinformation during hemodialysis: Effects of different dialyzer mem-

Cardiovascular response to hemofiltration 907

branes, Kidneymt 24:764—769, 198318. CHENOWETH DE, CHEUNG AK, WARD D, HENDERSON LW:

Anaphylatoxin formation during hemodialysis: Comparison of newand re-used dialyzers. Kidney mt 24:770—774, 1983

19. CHEUNG AK, CHENOWETH DE, OTSUKA D, HENDERSON LW:Compartmental distribution of complement activation products inartificial kidneys. Kidney mt (in press)

20, WALKER FJ, LINDSAY RM, SIBBALD WJ, PETERS 5, LINTON AL: Asheep model to study cardiopulmonary effects of blood—dialyzerinteractions. (Abstract) Kidney mt 23:164, 1983

21. HAKIM RM, BREILLATT J, LAZARUS JM, PORT FK: Complementactivation and hypersensitivity reactions to dialysis membranes. NEngI J Med 311:878—882, 1984

22. ROBSON M, POLLAK YE, KANT KS, CHAROENPANICH R, CATHEYM: There is a syndrome associated with the use of new dialyzers.(Abstract) 17th Ann Mtg ASN, p. 72A, 1984

23. HENDERSON LW, MILLER ME, HAMILTON RW, NORMAN ME:

Hemodialysis leukopenia and polymorph random mobility—a pos-sible correlation. J Lab Clin Med 85:191—197, 1975

24. BOHLER J, KRAMER P, SCHLAG G, REDEL H, GOTZE 0, SCHWARTZP: Leukozytenzahlund komplementaktivierung wahrend arterio—ve-noser und maschineller hamofiltration in arterio—venosehamofiltration, edited by KRAMER P, Gottingen, Vandenhoek,Ruprecht, 1982, p. 201

25. KIMURA G, VAN STONE JC, BAUER JH, KESHAVIAH PR: Asimulation study on transcellular fluid shifts induced by hemodial-ysis. Kidney mt 24:542—548, 1983

26. KESHAVIAH P, SHAPIRO FL: A critical examination of dialysis—in-duced hypotension. Am J Kid Dir 2:290—301, 1982

27. SHALDON 5, BALDAMUS CA, KOLK KM, LY5AGHT MJ: Of sodiumsymptomatology and syllogism. Blood Purification 1:16—24, 1983

28. HENDERSON LW, KOCH KM, DINARELLO CA, SHALDON S:Hemodialysis hypotension: the interleukin hypothesis. Blood Puri-fication 1:3—8, 1983