Intensive d ialysis Generally, modifi cation of the dialysis prescription in pregnancy has been recommended for patients treated with both hemodialy-present in high concentrations diff
Trang 1The physiology of dialysis is based on diffusive and convective transport Diffusion refers to the random movement of a solute down its concentration gradient It is by this means that the majority of urea and solute clearance is achieved Convection is that solute movement that occurs by means of solvent drag as water is removed, either by hydrostatic or osmotic force A lesser degree of clearance is obtained during fl uid removal by ultrafi ltration
Modes of d ialysis
Options for dialysis include hemodialysis and peritoneal dialysis, with the latter consisting of continuous ambulatory peritoneal dialysis (CAPD), continuous cycling peritoneal dialysis (CCPD), and nocturnal intermittent peritoneal dialysis (NIPD)
Hemodialysis
Hemodialysis requires a vascular access for extracorporeal therapy This is usually a surgically created artifi cial arteriovenous (AV) shunt or a native AV fi stula, although dual - lumen central venous catheters can be used temporarily (Figure 13.1 ) Products
of protein metabolism, such as urea nitrogen, potassium, and phosphate, are removed by both diffusion and convection across
a semipermeable dialyzer membrane, while ions such as bicar-bonate and calcium diffuse into the blood Fluid removal is accomplished by applying hydrostatic pressure across the dialyzer membrane The dialysis prescription for non - pregnant patients generally consists of 3 – 4 hours of hemodialysis thrice weekly, depending on urea generation rate and dialyzer solute clearance Heparinization is generally employed throughout the dialysis treatment
Peritoneal d ialysis
The various forms of peritoneal dialysis have in common the removal of these same metabolites and excess fl uid, albeit by dif-fusion and convective fl ow across the peritoneal membrane Surgical placement of a peritoneal catheter allows repeated access
to the peritoneal cavity (Figure 13.2 ) Removal of fl uid by osmotic force is achieved by instilling a hypertonic dialysate such as dex-trose solution into the peritoneal cavity Urea and other ions
develop, as are fl uid overload and uremic complications (Table
13.2 ) In patients with diabetes who often have other end - organ
damage, including autonomic neuropathy and vascular disease,
dialytic support may be required even earlier, when the GFR
reaches 15 mL/min
Table 13.1 Signs and symptoms of uremia
Organ involvement Subjective complaints Objective fi ndings
Neurologic Cognitive diffi culties Hyperrefl exia, asterixis
Sleep – wake reversal Seizures, encephalopathy Dysesthesias Peripheral neuropathy Hematopoietic Easy bruising and bleeding Anemia
Fatigue Prolonged bleeding time Gastrointestinal Metallic taste Angiodysplasia
Constipation
Musculoskeletal Weakness Carpal tunnel syndrome
Bone pain Bone fractures Myopathy
Cardiovascular Dyspnea Hypertension
Chest pain Pulmonary edema Pericarditis
Dermatologic Pruritus Cutaneous calcifi cations
Endocrine Decreased libido Decreased fertility
Dysmenorrhea, amenorrhea
Table 13.2 Indications for initiation of dialysis
Hyperkalemia
Metabolic acidosis
Volume overload
Uremic pericarditis
Uremic encephalopathy
Glomerular fi ltration rate (GFR) 5 – 10 mL/min
Figure 13.1 Hemodialysis
Trang 2cies in dialysis patients at their institution since 1965 [11] , although nearly one - third of their patients conceived before the onset of dialysis
There are many theoretical reasons to utilize peritoneal dialysis
in pregnancy, most notably of which is the steady - state removal
of uremic toxins (Table 13.3 ) This, coupled with easier fl uid removal, should minimize episodes of hypotension and thus pla-cental insuffi ciency Additional advantages of peritoneal dialysis often include less severe anemia, as well as better blood pressure control and more liberal dietary restrictions due to the continu-ous nature of the therapy [12 – 14] Furthermore, peritoneal dialy-sis obviates the need for systemic anticoagulation In diabetic patients, the use of intraperitoneal insulin can also facilitate strict glycemic control There have also been several case reports of successful intraperitoneal magnesium administration for the treatment of pre - eclampsia, maintaining a steady - state magne-sium serum level of approximately 5 mEq/L, although generally, alternative therapy may be recommended in renal failure to avoid magnesium toxicity [10,15]
Despite these apparent advantages of peritoneal dialysis, several unique complications exist, including catheter - related complica-tions such as laceration of the uterine vessels [16] and peritonitis Hou reported precipitation of preterm labor and delivery in two
of three patients secondary to peritonitis, but other reports suggest that the incidence of peritonitis is not increased in preg-nant versus non - pregpreg-nant patients [6] Peritoneal dialysis cath-eters have been placed as late as 29 weeks gestation In some patients, however, diffi culties with catheter obstruction and failure to drain necessitate placement of multiple catheters or conversion to hemodialysis It is also diffi cult to determine whether either method of dialysis actually precipitates preterm labor, because preterm labor has been described in the setting of both hemodialysis and peritoneal dialysis, as well as in CRF alone
Intensive d ialysis
Generally, modifi cation of the dialysis prescription in pregnancy has been recommended for patients treated with both
hemodialy-present in high concentrations diffuse from the peritoneal
vascu-lature into the dialysate, while calcium and a bicarbonate source
such as lactate move in the opposite direction Depending on the
mode of peritoneal dialysis selected, dialysate is instilled and
drained either manually or automatically at repeated intervals
throughout the day CAPD consists of approximately four manual
exchanges per day; the peritoneum is fi lled with several liters of
dialysate with each exchange, and the fl uid is drained 4 – 6 hours
later Both CCPD and NIPD utilize an automated cycler to
repeatedly fi ll and drain the peritoneum at shorter intervals
throughout the night CCPD differs in that it also includes a
daytime dwell for added clearance
Dialysis and p regnancy
Hemodialysis v s p eritoneal d ialysis
Both hemodialysis and peritoneal dialysis have been used
success-fully in pregnancy, although randomized prospective trials to
determine the optimal therapy have not been done Early reports
favored peritoneal dialysis, demonstrating greater fetal survival
than with hemodialysis, although these studies were limited by
small numbers of patients and the use of historical controls in
some: 67% vs 20% [4] , 83% vs 42% [9] , and 63% vs 20% [10]
This benefi t has not been borne out in more recent analyses and
likely refl ects improvement in outcome for pregnant patients on
dialysis as a whole The National Registry for Pregnancy in
Dialysis Patients (NPDR) documented virtually identical fetal
survival rates among 184 pregnancies for hemodialysis (39.5%)
vs peritoneal dialysis (37%) [1] Similar data are described by
Chan and colleagues (82% vs 72%) in their review of all
Figure 13.2 Peritoneal dialysis
Table 13.3 Mode of dialysis: advantages in pregnancy
Less work intensive for patient Stable biochemical environment
No risk of peritoneal catheter related complications
Continuous fl uid removal avoids hypotension
Adequate clearances late in gestation readily obtained
Allows liberal fl uid intake Permits continuous insulin administration in diabetes mellitus
No interruption in therapy needed after cesarean section No anticoagulation necessary
Permits administration of intraperitoneal MgSO 4 in pre - eclampsia
Hypertension easier to control Less severe anemia
Trang 3An additional benefi t of intensive dialysis is that a low level of azotemia should minimize the risk of polyhydramnios, although
it is not known if this will lead to improved outcome or a decreased incidence of preterm labor Polyhydramnios, seen in a high percentage of pregnancies, has been ascribed to the urea diuresis that normally occurs in utero due to high fetal levels of urea nitrogen, as well as to fl uid shifts that accompany intermit-tent hemodialysis [20,21] An increased frequency of hemodialy-sis in particular limits the large interdialytic weight gains often seen in hemodialysis patients, thus avoiding hypotension and enabling better blood pressure control by minimizing that com-ponent of hypertension that is volume mediated
Modifi cation of the d ialysis p rescription
With respect to hemodialysis, certain parameters of the dialysis prescription may warrant adjustment Specifi cally, a lower sodium dialysate of 134 mEq/L is recommended due to the mild physiologic hyponatremia of pregnancy Similarly, a bicarbonate concentration as low as 25 mEq/L may be necessary to avoid alkalemia, due to the repeated exposure to a bicarbonate dialysate and the concomitant respiratory alkalosis seen in pregnancy Acetate dialysis is not generally recommended because it has been associated with an increased frequency of hypotension, although there are no data in pregnancy A standard calcium dialysate can
be used with both hemodialysis and peritoneal dialysis, thus ensuring a net positive calcium balance suffi cient to meet fetal requirements Due to placental production of calcitriol, however, there is augmented gastrointestinal absorption of calcium from calcium - containing antacids; thus, serum calcium levels must be monitored to avoid hypercalcemia [22] With both methods of dialysis, one must also monitor closely for hypokalemia, which may develop with frequent dialysis
Changes in the effi cacy of peritoneal dialysis have not been noted during pregnancy In one patient studied there was no apparent change in peritoneal physiology or peritoneal blood
fl ow as assessed by the standard peritoneal equilibration test of glucose and creatinine [23] Similarly, Redrow and colleagues reported excellent ultrafi ltration in all patients throughout preg-nancy, and less than a one - third decrease in peritoneal solute clearance in three patients studied [10]
Dialysis and u teroplacental p erfusion
Doppler fl ow velocity measurements have been performed during and after hemodialysis in an attempt to assess the effect of hemo-dialysis on uteroplacental blood fl ow Results have been confl ict-ing, with studies reporting unchanged, worsened, and improved perfusion during dialysis as assessed by the systolic – diastolic ratio
or resistance index [24 – 26] In those patients studied, however, there was no evidence of uterine irritability or fetal distress as measured by external fetal monitoring during hemodialysis
Maternal c omplications
In the past, women with severe renal disease were often advised
to terminate pregnancies due to the belief that pregnancy carried
sis and peritoneal dialysis Although there are no fi rm guidelines,
it is the belief of most nephrologists that a more intensive dialysis
regimen is required during pregnancy to minimize fetal exposure
to uremic toxins and improve outcome This is based in part on
the fact that pregnancy outcome appears to be better in those
women who require initiation of dialysis due to a deterioration
of renal function during pregnancy, as well as among women
with signifi cant residual renal function who require dialysis
before conception [9] Infant survival as reported by the NPDR
was 73% in the former group of women, although only 40% in
those women who were already on dialysis at the time of
preg-nancy [1] Similar pregpreg-nancy success rates in dialysis patients
were reported by Bagon and colleagues based on a review of all
pregnancies in Belgium extending beyond the fi rst trimester [17]
Furthermore, pregnancy appears to be most common during the
fi rst year of dialysis, presumably related to the greater residual
renal function often present at the initiation of renal replacement
therapy There are reports of successful pregnancies in severely
uremic patients and patients on dialysis for more than 10 years,
as well as pregnancy failures in women treated with intensive
dialysis
Intensive dialysis corresponds to initiation of dialysis at levels
of BUN and creatinine approximately 60 – 70 mg/dL and 6 – 7 mg/
dL, respectively, with a goal of maintaining predialysis BUN levels
less than 50 mg/dL and 5 mg/dL, respectively [6,9] To maintain
such low levels of azotemia in pregnancy, dialysis patients may
require a signifi cant increase in total treatment time This is
espe-cially true in the third trimester when fetal urea production
increases and may account for as much as 540 mg/day [18] , a 10%
increase For women on hemodialysis, daily treatments of 5 or
more hours may be necessary to obtain adequate clearances late
in gestation As with hemodialysis, a patient ’ s treatment
require-ments may increase markedly with peritoneal dialysis as well,
especially because women in the latter half of gestation may be
unable to tolerate the standard dwell volumes due to abdominal
fullness A switch to CCPD with an increased frequency of small
volume exchanges and supplemental manual exchanges is often
required late in gestation to obtain adequate clearance A
combi-nation of hemodialysis and peritoneal dialysis may even be
indicated
Although the ideal dialysis prescription has yet to be
estab-lished, the National Registry data suggest a trend towards greater
infant survival and more advanced gestational age in those
women receiving more than 20 hours of hemodialysis weekly
[1,19] Others have confi rmed this fi nding, although no benefi t
was found in those women prescribed a higher dose of peritoneal
dialysis [11] Even though the number of weekly hemodialysis
treatments had no effect on outcomes in some studies,
perform-ing dialysis 4 to 6 times per week may allow for better fl uid and
blood pressure management and may also decrease the risk of
polyhydramnios which can lead to preterm labor and delivery
While no guidelines exist with regard to evaluating the adequacy
of dialysis, a minimum combined renal and dialytic clearance of
15 mL/min is recommended
Trang 4period [31] Three maternal deaths have been reported to date, one of which was the result of lupus cerebritis [1]
Polyhydramnios is a common fi nding, reported in between 29% and 67% of pregnancies in CRF patients [6] This may be caused by the rapid removal of solutes during hemodialysis and shifting of free water into the amniotic space or an increased fetal osmotic diuresis because of the increased maternal urea concentration
Preterm delivery is an expected outcome in these patients as well, with the mean age of delivery being only 32 weeks gestation [32] Early delivery may be because of spontaneous preterm labor, and polyhydramnios may contribute to this, the result of fetal distress, intrauterine growth restriction, pre - eclampsia, or placental abruption
Fetal c omplications
The likelihood of fetal survival beyond the neonatal period is better than previously believed (Table 13.5 ) Surveys conducted
by the EDTA [3] , the American Nephrology Nursing Association [9] , as well as a group in Saudi Arabia [5] reported a fetal viability
of 20 – 30% in those pregnancies that were not electively termi-nated The EDTA survey revealed that greater than 50% of preg-nancies resulted in spontaneous abortion [3] Hou et al noted a comparable incidence of 54% fetal loss, including spontaneous abortion, stillbirth, and neonatal death [21] ) Virtually all infants delivered were premature, and approximately 20% were growth restricted When stratifi ed according to year, however, survival was greater than 50% in those pregnancies occurring since 1990 Another study supports improved neonatal survival and sum-marized the outcomes of 111 pregnancies in patients receiving chronic hemodialysis and reported that 71% (79/111) of these infants who were born survived [6]
As noted previously, polyhydramnios, possibly attributed to the fetal urea diuresis, is seen with greater frequency in renal failure and may contribute to the high incidence of prematurity Additionally, a urea - induced diuresis following delivery may result in volume depletion in the neonatal period
Early reports failed to identify an increased incidence in con-genital anomalies [3,9] However, the NPDR reported on 11 infants with congenital anomalies among 55 live births [1] Not surprisingly, there was also a high proportion of infants with developmental delays or long - term medical problems docu-mented at follow - up, the latter possibly attributable to problems
a high risk of maternal complications and a low success rate
Because there are defi nite risks to both the mother and the fetus
as a result of CRF requiring dialysis in pregnancy, these patients
should be counseled before conception if at all possible Potential
complications include an accelerated decline in renal function,
accelerated hypertension, an increased risk of superimposed pre
-eclampsia, polyhydramnios, worsened anemia often requiring
transfusion, hemodialysis access thrombosis, and an increased
incidence of abruptio placentae (Table 13.4 ) The latter cannot
be ascribed solely to the use of heparin during hemodialysis
because it has been seen with greater than normal frequency in
patients on peritoneal dialysis as well
Pregnancy has been associated with a permanent decline in
renal function in a relatively small percentage of patients with
mild renal failure, defi ned by a serum creatinine of < 1.4 mg/dL
This risk may be increased signifi cantly in those women with
moderate or severe renal failure, especially in the setting of
uncontrolled hypertension It is always important to rule out
readily reversible causes of declining renal function, such as
volume depletion, pyelonephritis, and obstruction One report of
37 pregnant women with moderate or severe renal failure, defi ned
as a serum creatinine greater than 1.4 mg/dL, demonstrated a
deterioration in renal function, defi ned as greater than a 50% rise
in creatinine, in 16% [27] Five of these six women also suffered
from poorly controlled chronic hypertension, and a clinical
diag-nosis of superimposed pre - eclampsia was established in nearly
60% overall Similarly, a more recent review encompassing more
than 80 pregnant women with renal failure demonstrated
acceler-ated hypertension in nearly 50% and an acceleracceler-ated decline in
renal function in more than one - third [28] Hou reviewed these
studies along with fi ve others, all of which confi rmed the increased
incidence of accelerated renal failure in women with a serum
creatinine greater than 1.4 mg/dL at the time of conception [29]
Severe hypertension and proteinuria were predictive of an
accel-erated course in more than 20% of patients with moderate to
severe renal failure due to a wide range of primary glomerular
diseases [30] Of interest, a review of pregnancy in patients with
diabetic nephropathy, defi ned as nephrotic - range proteinuria
and severe hypertension, failed to describe an accelerated loss of
renal function during pregnancy, although nearly one - third of
women had reached ESRD or died during the 3 - year follow - up
Table 13.4 Renal failure and pregnancy: maternal complications
Accelerated decline in renal function
Accelerated hypertension
Superimposed pre - eclampsia
Preterm labor
Worsened anemia
Hemodialysis access thrombosis
Abruptio placentae
Spontaneous abortion and second - trimester fetal loss
Table 13.5 Renal failure and pregnancy: fetal complications
Spontaneous abortion and fetal loss (50%) Fetal/neonatal death (21 – 33%)
Preterm delivery ( > 80%) Intrauterine growth restriction (20%) Polyhydramnios (29 – 67%) Maternal hypertension (35 – 72%)
Trang 5allow for normal fetal development The recommended protein intake is 1.5 g/kg/day in hemodialysis and 1.8 g/kg/day in perito-neal dialysis and daily caloric intake increased to 30 – 35 kcal/kg/ day as well [29] Increasing delivery of dialysis is recommended for worsening azotemia rather than strict protein restriction Supplementation of water - soluble vitamins, which are removed during dialysis, is recommended, as well as supplementation with folate, zinc, and iron Specifi cally, it is important to monitor hemoglobin and iron stores on a regular basis as oral iron supple-mentation is often insuffi cient given the increased requirements during pregnancy Intravenous iron has been given to pregnant dialysis patients without adverse outcomes as mentioned previ-ously [35] Standard prenatal vitamins, which may contain excess vitamin A, are best avoided
Antepartum m anagement
Care during pregnancy for patients on dialysis should include a multidisciplinary team with at least initially a nephrologist and maternal - fetal medicine specialist Given the extremely high like-lihood of a preterm delivery, it is also important to make the neonatologist and the neonatal intensive care unit aware of the patient as these infants may also demonstrate some degree of azotemia after delivery In addition, the patient should be coun-seled on the likely complications and possibility of premature delivery
Early in pregnancy, care should be focused on dating the preg-nancy as accurately as possible, which is diffi cult given the advanced gestational age at which patients often present Dialysis time should be increased and anemia monitored closely which will require increasing the dose of erythropoietin as discussed before Dietary alterations, including increased folate supplemen-tation and protein intake, should also be instituted
Hypertension is a common comorbidity and is seen in up to 80% of pregnant dialysis patients [6] Many antihypertensive medications are considered safe in pregnancy and may be uti-lized; however, the angiotension - converting enzyme inhibitors and angiotensin receptor blockers are contraindicated in preg-nancy secondary to associations with renal dysplasia, neonatal anuria, and stillbirth [36,37] Some of the older medications that have been described to treat hypertension in pregnancy include methyldopa and hydralazine and these are acceptable to use Even though there have been reports of concerns about intrauterine growth restriction and neonatal bradycardia and hypoglycemia with the use of some beta - blockers, the best evidence for this was associated with atenolol Other beta blockers, such as labetalol, are recommended by some as fi rst - line therapy for treatment of hypertension in pregnancy [38] Regardless of which medication
is used, treatment of hypertension is essential during pregnancy for these patients
In addition, the physician should monitor for urinary tract infections and aggressively treat even asymptomatic bacteruria as the risk of pyelonephritis is quite high when this is present and
often encountered with premature birth Unfortunately, there is
little additional long - term follow - up on infants exposed to
azotemia in utero with regard to physical and intellectual
development
Anemia
Anemia develops during pregnancy largely due to an increase in
plasma volume of 3 – 4 L without a corresponding increase in red
cell mass [6] In patients with renal failure, the picture is
compli-cated by a relative defi ciency in erythropoietin production by the
diseased kidneys, as well as shortened red cell survival, bone
marrow suppression by uremic toxins, and possible
superim-posed nutritional defi ciencies The severe anemia that was typical
of ESRD in the past is now treated successfully in most cases with
recombinant human erythropoietin (rHuEpo) Furthermore,
correction of the anemia of ESRD may result in return of regular
menses due to resolution of hyperprolactinemia, and conception
may follow [8]
Recombinant human erythropoietin has been studied in
preg-nant animals at doses used clinically without apparent
complica-tions Hou reported on 11 patients with CRF treated with rHuEpo
in whom no congenital anomalies were seen and no rHuEpo
could be detected in the cord blood [9] All of the women required
an increase in their dose of rHuEpo, compared with
prepreg-nancy, and three still required blood transfusions during
pregnancy Only one woman experienced severe hypertension
complicating therapy, although several required additional
anti-hypertensive medications Additional reports have yielded similar
results [1,17,33,34] It is accepted by most obstetricians that a
hemoglobin less than 6 g/dL is associated with increased perinatal
mortality and maternal morbidity secondary to high - output
failure Given this fact, as well as the increased risk of bleeding
complications in uremia due to platelet dysfunction, and the
overwhelming likelihood of preterm delivery, the
recommenda-tion for women with renal disease is an empirical 50% increase
in rHuEpo dose once the pregnancy is detected, with a goal of
maintaining the hemoglobin at more than 10 g/dL [9] Most
patients require oral iron supplementation or intermittent
intra-venous iron, because iron defi ciency eventually develops in most
patients successfully treated with rHuEpo Although intravenous
iron has been used without incident in at least 20 patients, it is
generally recommended only if iron defi ciency persists despite
oral therapy
Dietary g uidelines
Dietary restrictions in renal failure generally consist of modest
protein restriction, as well as restriction of potassium, phosphate,
and sodium intake Fluids are restricted to 1 L daily, with more
liberal intake permitted in those with substantial residual urine
output In pregnancy, however, protein intake is liberalized to
Trang 6general, the route of delivery should be determined by the fetal status and cesarean section reserved for normal obstetric indications
In the postpartum period, the patient must be monitored closely as the provider should anticipate signifi cant fl uid shifts in the fi rst week after delivery
Pregnancy and a cute r enal f ailure
Most of the literature pertaining to dialysis in pregnancy concerns those women with CRF or ESRD There are, however, a number
of case reports of dialysis for ARF in pregnancy Hemodialysis has been the primary form of dialysis utilized, both for ARF and for acute ingestion of toxic substances [44 – 46] Because the inci-dence of ARF itself has fallen to less than 1% of pregnancies in developed countries, the need for acute dialysis is rare [47] This topic is addressed in more detail in Chapter 28
Summary
Although pregnancy remains uncommon in women with severe CRF or ESRD, it is nevertheless a possibility, especially with modern treatment With intensive management by the obstetri-cian and nephrologist, the likelihood of a favorable outcome can
be maximized This will generally entail early initiation of dialysis
in women with CRF or intensifi ed dialytic therapy in those already requiring renal replacement therapy
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untreated Generally, urine cultures can be done every 4 – 6 weeks
and patients treated as appropriate
A new approach to the prevention of recurrent preterm
deliv-ery may also have some benefi t in dialysis patients Two
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peritoneal dialysis for several days to allow healing of the
abdomi-nal wall and prevent dialysate leak or hernia formation Peritoneal
dialysis can be reinitiated using smaller dwell volumes initially,
with a progressive increase in volume as tolerated If necessary,
temporary hemodialysis can be performed in the interim In
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13 Changs H , Miller MA , Bruns FJ Tidal peritoneal dialysis during
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14 Castillo AA , Lew SQ , Smith AM , Bosch JP Women issues in female
patients receiving peritoneal dialysis Adv Ren Replace Ther 1999 ; 6 :
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15 Elliot JP , O ’ Keeffe DF , Schon DA , Cherem LB Dialysis in pregnancy:
a critical review Obstet Gynecol Surv 1991 ; 46 : 319 – 324
16 Hou SH Pregnancy and birth control in CAPD patients Adv Perit
Dial 1993 ; 9 : 173 – 176
17 Bagon JA , Vernaeve H , de Muylder X et al Pregnancy and dialysis
Am J Kidney Dis 1998 ; 31 : 756 – 765
18 Hou SH , Grossman SD Pregnancy in chronic dialysis patients Semin
Dial 1990 ; 3 : 224 – 229
19 Hou S Pregnancy in dialysis patients: Where do we go from here?
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20 Nageotte MP , Grundy HO Pregnancy outcome in women requiring
chronic hemodialysis Obstet Gynecol 1988 ; 72 : 456 – 459
21 Hou SH Pregnancy in women on haemodialysis and peritoneal
dialy-sis Bailliere ’ s Clin Obstet Gynaecol 1994 ; 8 : 481 – 500
22 Grossman S , Hou S Obstetrics and gynecology In: Daugirdas JT ,
Ing TS , eds Handbook of dialysis New York : Little, Brown , 1994 :
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23 Lew SQ , Watson JA Urea and creatinine generation and removal in
a pregnant patient receiving peritoneal dialysis Adv Perit Dial 1992 ;
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24 Weiner Z , Thaler I , Ronen N , Brandes JM Changes in fl ow velocity
waveforms in umbilical and uterine artery following haemodialysis
Br J Obstet Gynaecol 1991 ; 98 : 1172 – 1173
25 Jakobi P , Weiner Z , Geri R , Zaidise I Umbilical and arcuate uterine
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26 Krakow D , Castro LC , Schwieger J Effect of hemodialysis on uterine
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27 Cunningham FG , Cox SM , Harstad TW et al Chronic renal disease
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Trang 8Critical Care Obstetrics, 5th edition Edited by M Belfort, G Saade,
M Foley, J Phelan and G Dildy © 2010 Blackwell Publishing Ltd.
Katherine W Arendt
Mayo Clinic, Rochester, MN, USA
Introduction
Cardiopulmonary bypass (CPB) is a commonly used and often
necessary technique during cardiac surgery It results in signifi
-cant alterations in patient physiology with virtually every organ
system affected Some of the prominent adverse effects include:
(i) profound alterations in coagulation (dilution of all clotting
factors, intense heparinization, platelet dysfunction); (ii)
distur-bances in cardiovascular function (hypotension, non - pulsatile
blood fl ow, myocardial ischemia and cardiac stunning,
arrhyth-mias); and (iii) a signifi cant generalized systemic infl ammatory
response Systemic embolization of particulate material occurs,
including marrow and fat spilled into the chest when the sternum
is split Air embolization also frequently occurs Embolic
phe-nomena are thought to be major contributors to the signifi cant
risk of cerebrovascular accident (2 – 6%) and neurocognitive
dysfunction (20 – 60%) [1 – 3] In addition, the management of
patients requiring CPB frequently includes the use of
hypother-mic techniques, invasive monitoring, and the administration of
a variety of cardiovascular drugs Not infrequently, complications
involving one or more major organ systems are experienced
The application of “ off - pump ” coronary artery bypass for
patients with coronary artery disease has become popular to a
great degree because of the inherent risks of CPB [4] However,
off - pump approaches are not available for patients with cardiac
valvular surgical disease, the cardiac pathology that most often
affects the pregnant patient Closed mitral valvotomy in order to
avoid cardiopulmonary bypass (CPB) in pregnancy has been
widely described [5 – 7] Likewise, more and more cardiac
proce-dures are being done without requiring CPB with percutaneous
modalities However, fetal radiation exposure during fl uoroscopy
remains a prohibitive factor for percutaneous techniques during
pregnancy Echocardiography imaging alone without fl
uoro-scopy has been described in percutaneous balloon valvuloplasty [8,9] , but experience in this technique is limited For now, many cardiac procedures will continue to require parturients to undergo CPB for open heart or aorta surgeries
The fi rst reports of cardiac surgery during pregnancy were published in 1952 and involved 11 closed mitral commissuroto-mies performed during pregnancy [10 – 13] In 1958, CPB was fi rst performed on a pregnant woman [14] Since this time, multiple cases and series have been published describing CPB in pregnancy [15] Maternal mortality for cardiac surgeries does not appear to
be affected by pregnancy, but the risk of fetal loss is signifi cant
Maternal and f etal r isks of c ardiopulmonary
b ypass
For understandable reasons, no well - controlled studies have been reported assessing the impact of CPB on the pregnant patient, the fetoplacental unit, or fetal outcome In addition, many of the existing case series date back to the late 1950s and early 1960s Approaches and techniques that cardiac patients receive continue
to change Thus, many conclusions regarding management and outcome must be viewed with caution
From the data that are available, pregnant women do well during CPB with a variable mortality rate similar to that for non pregnant patients: 1.4 – 13.3% Fetal loss, however, is signifi cant, with rates ranging from 16% to 38.5% These quoted mortality rates are from multiple published series [16 – 22] The fi rst series
of CPB in pregnancy was published in 1969 and described 20 cases with a single (5%) maternal death and 7 (33%) fetal deaths [16] The highest fetal mortality was reported in a series of 15 parturients in Mexico undergoing open heart surgery from 1972
to 1998 with 2 (13.3%) maternal deaths and 5 (38.5%) fetal deaths [22] In the most recent literature, Weiss et al (1998) [23] describes 59 cases of CPB in pregnancy reported in the literature from 1984 to 1996 with 3 (5%) maternal deaths and a fetal/ neonatal mortality rate of 29% They also noted a 25% rate
of premature births
Trang 9Whether by thoracotomy or a percutaneous balloon technique, mitral commissurotomy instead of open valve repair or replace-ment is associated with a signifi cant likelihood of patients requir-ing additional surgery at a later date Mangione and coworkers [28] published favorable results with only 9% of their 23 patients requiring repeat valvuloplasty after 8 years of follow - up Fawzy and colleagues [29] reported that 16% of their patients under-going mitral balloon valvuloplasty developed restenosis over
a follow - up period of 9 years In the series of Vosloo and Reichart [5] , 22% of patients receiving closed commissurotomy required an additional cardiac surgery during a follow - up period lasting from 5 to 17 years These data led some to recommend that parturients undergo the open valve repair or replacement requiring CPB during pregnancy
The performance of coronary artery bypass grafting (CABG) without CPB ( ‘ off - pump ’ CABG, beating heart CABG) avoids the risks of CPB Silberman and coworkers [33] describe a case of coronary artery bypass grafting performed on a beating heart without the use of CPB on a patient at 22 weeks gestation status after spontaneous dissection of the left anterior descending artery She subsequently gave birth to a healthy term baby Although long - term (10 years) results of beating heart CABG are not yet known to be equal to that of traditional CABG techniques,
it has gained wider acceptance This is because studies to date indicate that off - pump CABG techniques provide complete revascularization, reduced myocardial injury, less coagulopathy, decreased transfusion requirements, higher hematocrit at dis-charge, and shorter hospital length of stay [34]
Timing c ardiac s urgery d uring p regnancy
Cardiologists who care for women with heart disease of child-bearing age counsel these patients about the risks of pregnancy and optimizing their condition before conception Such optimi-zation is not always possible, pregnancy is not always planned, and often the existence or extent of cardiac disease is unmasked
by the cardiovascular changes of the pregnancy itself Therefore, cardiologists and cardiovascular surgeons are left trying to decide
if surgical intervention is going to be necessary before term deliv-ery and, if so, the optimal gestational age to intervene
Typically, in obstetric medicine, what is in the best interest of maternal health is in the best interest of her fetus This may not
be the case when deciding the timing of surgery in the parturient with a deteriorating cardiac status In a systematic review from
1984 to 1996, Weiss et al compared maternal and fetal outcomes
in cardiac surgeries performed during pregnancy, those per-formed immediately after delivery of the neonate, and those in which the surgery was delayed until after the postpartum period [23] Fetal mortality was greatest (about 30%) in those surgeries performed during pregnancy, with two (5%) fetal deaths when the mother underwent surgery immediately after delivery, and no fetal deaths when the mother delayed surgery until the post-partum period In contrast, however, the maternal mortality
With such signifi cant fetal death rates, it is likely that fetal
morbidity is similarly high in the fetal survivors of CPB At
present, there are no long - term follow - up studies assessing the
probable deleterious effects of CPB on those with fetal exposure
to CPB The confounding effects of fetal exposures to their
mother ’ s cardiac disease, pharmacologic management, and
possibly other cardiac interventions would make such
assess-ments diffi cult
In spite of the signifi cant number of series that have been
published describing mortality rates associated with CPB in
preg-nancy, few correlations can be made with CPB techniques and
reduction in maternal and fetal morbidity and mortality The
optimal gestational age at the time of surgery, fetal heart rate
monitoring, high fl ow CPB, normothermic CPB, and possibly
pulsatile CPB have all been proposed to improve outcome
Cardiac p rocedures a voiding c ardiopulmonary
b ypass
The physiologic changes of pregnancy involve increases in cardiac
output Because of this, left - sided obstructive lesions such as
mitral or aortic valvular stenosis are more likely than other
val-vular lesions to cause complications during pregnancy [24]
Likewise, most available reports of cardiac surgery during
preg-nancy involve valve repair or replacement
With the signifi cant fetal risks CPB, parturients with mitral
stenosis may be evaluated for candidacy for closed mitral
com-missurotomy In this procedure, CPB is not necessary Instead,
the cardiothoracic surgeon performs an anterior lateral
thora-cotomy, places his or her fi nger inside the left atrium, guides a
dilator across the mitral valve orifi ce and splits open the narrowed
mitral valve Early collective experience in over 500 patients
undergoing closed mitral commissurotomy before 1965 was
asso-ciated with maternal mortality of under 2% and fetal mortality
under 10% [25] Multiple more recent studies have confi rmed
that this procedure is lower risk for the fetus than open
proce-dures requiring CPB [5,18,20]
Presently, a more common technique to avoid CPB in the
parturient with mitral stenosis is percutaneous balloon mitral
commissurotomy [26 – 30] Mishra and colleagues (2001) [31]
reported improved hemodynamics and symptoms in 81 out
of 85 severely symptomatic pregnant women with critical mitral
stenosis who underwent this procedure They noted that although
the procedure was safe and generally effective, mitral
regurgita-tion increased by 1 – 2 grades in 18 of the 85 patients Abouzied
and coworkers (2001) [32] reported similar results in 16 pregnant
women with severe mitral stenosis who underwent balloon
mitral commissurotomy They also reported no immediate
detrimental effects of radiation exposure related to fl uoroscopy
on the fetuses In order to avoid fetal radiation exposure,
echocardiography imaging alone without fl uoroscopy has been
described for this procedure [8,9] Few centers offer this
technique
Trang 10rate depending upon the lesion Therefore, if it is determined that
a parturient may not survive into the third trimester, early second trimester may be the ideal time to perform surgery This prevents further deterioration of cardiac status but exposes the fetus to anesthesia and CPB after organogenesis has occurred Others suggest that cardiac surgery is best done between 24 and 28 weeks gestation after the attainment of fetal viability With this timing, neonatal intensive care facilities should be available and if fetal distress is detected, cesarean delivery could occur perioperatively
Cesarean delivery during CPB should not occur because of the
signifi cant bleeding risk to the mother during heparinization Successful cesarean delivery just before CPB has been described [16,40]
Uteroplacental p erfusion and c ardiopulmonary
b ypass
Uteroplacental blood fl ow (UPBF) is the major determinant of oxygen and other essential nutrient transport to the fetus A direct correlation between uterine blood fl ow (UBF) and fetal oxygen-ation has been demonstrated in both animal models and humans [41,42] UPBF is derived primarily from uterine arteries, with a smaller contribution (of unknown signifi cance) coming from the ovarian arteries The uterine arteries are branches of the internal iliac arteries Uterine artery blood fl ow (UABF) increases two - to threefold in pregnancy and can represent up to 12% of the cardiac output Increases in UBF during pregnancy are due to both physi-cal (increased diameter of the uterine artery) and physiologiphysi-cal (decreased responsiveness of the uterine artery to endogenous circulating vasoconstrictors) mechanisms Selective uterine artery relaxation during pregnancy may be the result of vasodilators released from its endothelium, such as PGI 2 or nitric oxide, or local hormonal actions, which diminish the activity of certain intracellular enzymes that mediate vasoconstriction
Therefore, under normal circumstances during pregnancy, the uterine arteries are maximally dilated and there is no autoregula-tion of UABF Systemic hypotension results in vascular dilaautoregula-tion
to maintain blood fl ow for autoregulated organs such as the brain and kidneys In contrast, the placental vasculature cannot further vasodilate in response to hypotension, and decreased uteropla-cental perfusion and, if signifi cant, fetal hypoxia results Fetoplacental suffi ciency is related to fetal heart rate (FHR) with acute insuffi ciency resulting in fetal bradycardia and long term insuffi ciency with subsequent fetal acidosis resulting in fetal tachycardia with minimal beat - to - beat variability on FHR tracing
An example of FHRs throughout CPB is provided in Figure 14.1 The onset of CPB is typically characterized by fetal bradycardia, while the conclusion of CPB demonstrates fetal tachycardia with minimal beat - to - beat variability [43,44]
The cause of this initial fetal bradycardia is thought to be sec-ondary to placental hypoperfusion because it has been found reversible in most cases by increasing the perfusion rate Other theories for this initial fetal bradycardia have included maternal
increased when the surgery was delayed until after birth
Therefore, it seems that the fetus benefi ts most from delaying
maternal cardiac surgery until after birth, but the mother may
benefi t from an earlier intervention, while still pregnant Clearly,
these retrospective data may be confounded by the fact that the
sickest parturients were unable to wait for surgery and had to be
treated earlier Nonetheless, the challenge of determining the
optimal timing for a deteriorating parturient is diffi cult and this
study illustrates the consequences of this important clinical
judg-ment: decreasing maternal risk by intervening early may result in
fetal demise while delaying until after delivery may result in
maternal death
In determining the optimal gestational timing for cardiac
surgery, the effects of general anesthesia need to be considered
separately from the effects of CPB The most thorough evaluation
of the risks of all types of anesthesia and surgery during
preg-nancy retrospectively evaluated a population of 720 000 pregnant
women who underwent 5405 surgical procedures [35] The
inci-dence of congenital malformations or stillbirths was not increased
in the offspring in the women who underwent surgery, regardless
of gestational age at the time of surgery The incidence of
prema-turity, low - birth - weight infants and the rate of infant death
within 168 hours of birth was slightly increased This increase,
however, was not linked to the gestational age at the time of
surgery Further, patients who require surgery may have
underly-ing illness that affects the health of their pregnancy This
con-founds the results making it diffi cult to determine the singular
risk of surgery during pregnancy Very few of the cases in this
series involved CPB Therefore, although we can state that
anes-thesia at any time during pregnancy is probably safe, the risks of
fetal exposure to CPB at various times during gestation are less
clear
No relationship between gestational age at the time of CPB
surgery and fetal morbidity and mortality can be conclusively
determined at this time There is, however, a case report of a
parturient undergoing mitral valve surgery at the 6th week of
gestation with fetal hydrocephalus detected at 18 weeks gestation
by ultrasound [36] Some quote this case along with a case from
the 1960s as reason to avoid surgery requiring CPB during the
fi rst trimester [37,38] A case report of fetal hydrocephalus and
hydrops has also been described after CPB at 19 weeks gestational
age, illustrating that the second trimester is not free from fetal
risk [39] In retrospective series of parturients undergoing CPB,
fetal mortality has been described during every trimester of
gesta-tion [16 – 18,22,23] Therefore, although the risks of anesthesia
and CPB during fi rst trimester and organogenesis would
theoreti-cally increase fetal risks, there are no data to support this theory
None the less, many anesthesiologists, cardiologists, obstetricians
and cardiothoracic surgeons recommend that surgery, especially
surgery requiring CPB, be delayed until after organogenesis
during the fi rst trimester of pregnancy
During late second trimester, the cardiac output of the
parturi-ent peaks As a result, if the parturiparturi-ent is doing poorly at the
beginning of the second trimester, she will likely further