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0959-289X/$ - see front matter c 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ijoa.2013.03.016
REVIEW ARTICLE
www.obstetanesthesia.com
ABSTRACT
Parturients with renal insufciency or failure present a signicant challenge for the anesthesiologist. Impaired renal function compromises fertility and increases both maternal and fetal morbidity and mortality. Close communication amongst medical specialists, including nephrologists, obstetricians, neonatologists and anesthesiologists is required to ensure the safety of mother and
child. Pre-existing diseases should be optimized and close surveillance of maternal and fetal condition is required. Kidney function
may deteriorate during pregnancy, necessitating early intervention. The goal is to maintain hemodynamic and physiologic stability
while the demands of the pregnancy change. Drugs that may adversely affect the fetus, are nephrotoxic or are dependent on renal
elimination should be avoided.
c 2013 Elsevier Ltd. All rights reserved.
Introduction
Chronic kidney disease (CKD) is diagnosed in 0.030.12%
of pregnancies.1 The low incidence may be a direct effect
of renal disease on fertility, or represent underreporting
of the condition. The impact of maternal renal disease
on perinatal outcome will depend on the degree of renal
insufciency and co-morbid conditions at the time of presentation.2 A recently published systematic review included 13 observational studies with over 26 000
pregnancies.3 Parturients with CKD had up to a ve-fold
higher incidence of morbidity, including gestational hypertension, preeclampsia, eclampsia and maternal mortality,
when compared to parturients with normal pregnancies.
Similarly, the risk of adverse fetal outcome was two times
greater in women with CKD.3 However, there are limited
data regarding the peripartum management of these patients. The purpose of this review is to examine the peripartum anesthetic management of parturients with
underlying CKD presenting to the labor and delivery unit.
224
Table 1
Function
Change
Manifestation
Acidbase regulation
Water metabolism
Volume regulation
Sodium metabolism
Tubular transport
Pathophysiology
The pathophysiology by which pregnancy exacerbates
renal disease is unknown. Pre-existing renal disease
may be a precursor for platelet aggregation, formation
of brin thrombi, microvascular coagulation, and endothelial dysfunction in the kidney. The superimposition
of a preeclamptic microangiopathy on kidneys with
pre-existing dysfunction may lead to poorly reversible
or persistent renal damage.10 There are many causes of
CKD or end-stage renal disease, each with its own pathophysiologic disease mechanism. More common causes
include type 1 diabetes mellitus, glomerulonephritis,
hypertension, lupus nephritis, immunoglobulin A
(IgA) nephropathy, and polycystic kidney disease.2
The effects of renal failure and anesthetic implications
are shown in Table 2.
V. Chinnappa et al.
Table 2
225
Cardiovascular
Neurological
Pulmonary
Gastrointestinal
Hematological
Metabolic
stricted intrauterine growth, acute and chronic fetal distress, pre-term birth, respiratory difculty in the newborn, intensive care admission and intrauterine or
neonatal death.12 The outcome of pregnancy in women
with CKD depends on the degree of renal impairment,
the presence of hypertension or proteinuria, infection
and preeclampsia.
Women with preserved renal function and well-controlled blood pressure have favorable maternal and fetal
outcomes. Those with mildly elevated creatinine, in the
range of 1.21.4 mg/dL (106124 lmol/L) have a small
risk for a decline in renal function. Those with moderate
renal insufciency (serum creatinine 1.42.5 mg/dL, or
124220 lmol/L) are at 2030% increased risk of preeclampsia and preterm delivery. Of these women,
approximately 50% have a pregnancy-related decrease
of 25% or more in creatinine clearance, which may persist or worsen after delivery. Women with severe renal
dysfunction, dened as a creatinine concentration
>2.5 mg/dL (220 lmol/L), should be discouraged from
conceiving because 70% will experience preterm delivery, 40% will develop preeclampsia, and 40% will experience pregnancy or postpartum deterioration in renal
function necessitating dialysis.1216
Maternal blood pressure at conception is an important predictor of pregnancy outcome. In the absence
of hypertension, there is signicantly less chance of irreversible deterioration in renal function during pregnancy. However, hypertension present at conception
may be associated with fetal loss. Jungers et al. reported
that fetal loss increased 10-fold when hypertension was
present at conception, despite serum creatinine concentrations similar to normotensive controls.17 Although
blood pressure control is important, some antihypertensive medications, such as angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers, are
contraindicated in pregnancy due to increased risk to
the fetus.18 Antihypertensive medications considered
safer include alpha methyldopa, labetolol, or
nifedipine.5
Proteinuria can be an indicator of renal impairment
in pregnancy. Stettler and Cunningham reviewed 65
pregnancies in 53 asymptomatic women with signicant
proteinuria (>500 mg/24 h) but no known pre-existing
renal disease or diabetes.19 Renal insufciency co-existed in 62% of the women and 40% had chronic hypertension; preterm delivery occurred in 50% and fetal
growth restriction in 25%. About 20% of these women
progressed to end-stage renal disease within ve years.19
Infections are common during pregnancy in women
with CKD. A urinary tract infection may cause rapid
decline in renal function.20 Preeclampsia is a marker
for an increased risk of subsequent end-stage renal disease. The risk is increased by 4.7-fold when associated
with preeclampsia.21
Diabetes
Patients with overt diabetic nephropathy, with microalbuminuria, well-preserved renal function and normal
blood pressure have a good prognosis for pregnancy,
although are at increased risk of preterm delivery, preeclampsia and urinary infection.5 Monitoring of renal
function in diabetics is mandatory.23
226
preeclampsia, with deteriorating renal function, hypertension, worsening proteinuria, a decrease in GFR,
thrombocytopenia and hypertension. Treatment for lupus are includes additional corticosteroids, which may
worsen preeclampsia. Additional symptoms of a lupus
are, such as presence of the typical rash, arthritis or serositis, help differentiate the conditions. A urine sediment
and hypocomplementemia are not features of preeclampsia, whereas deteriorating liver function tests occur in preeclampsia but are not characteristic of lupus activity.24
Chronic pyelonephritis
Chronic pyelonephritis is dened as a nephropathy associated with recurrent urinary tract infection, often in
association with urinary tract abnormalities (e.g. vesico-ureteric reux). Pre-existing chronic pyelonephritis
may worsen in pregnancy and have an adverse effect
on pregnancy outcome.5
V. Chinnappa et al.
Pregnancy does not cause irreversible dysfunction if
the function of the transplanted organ was stable before
pregnancy,30 but monitoring renal function throughout
pregnancy is mandatory. Several studies have compared
serum creatinine as an index of graft function before
and after pregnancy.31 Generally, observations in patients with CKD are similar to those in kidney transplant
recipients, in whom a serum creatinine <1.3 mg/dL
(115 lmol/L), independent of immunosuppressive drug
use, confers little risk of short-term graft loss.31 Davison
reported that a serum creatinine >1.5 mg/dL (135 lmol/L)
and proteinuria >500 mg/24 h signicantly increase the
risk of irreversible graft loss.32 Pregnancy has minimal
effect on allograft function, provided serum creatinine is
not elevated. The incidence of rejection during or immediately after pregnancy is not increased compared to nonpregnant transplant patients, but fetal outcome is less
favorable.29 The incidence of live birth is between 55%
(United States Renal Data System database) and 80%
(National Transplantation Pregnancy Registry, UK). In
addition to fetal loss, there is a risk of intrauterine growth
restriction, prematurity and developmental delay.29
The location of the implanted kidney does not obstruct normal vaginal delivery, which is achieved in
50% of women.33 In the absence of renal dysfunction
and hypertension, anesthetic management of the parturient with a renal transplant is similar to that of
the otherwise healthy parturient. Symptoms and signs
of side effects from immunosuppressive and chronic
corticosteroid use should be sought. The drugs used
preoperatively and intraoperatively to prevent acute
rejection themselves have serious side effects that require close monitoring of blood glucose and cardiovascular function. Since renal transplantation greatly
increases the risk of infection, it is important where
possible to avoid invasive monitoring. Meticulous sterile technique should be used to prevent patient crosscontamination.
227
indices, including serum urea, creatinine, electrolytes,
albumin, full blood count, urinalysis and urine culture.
An assessment of proteinuria is necessary, and can be
performed using a 24-h urine collection or by a spot test
for total urine protein/creatinine ratio. Total protein/
creatinine ratio has been shown to estimate accurately
24-h urine protein in non-pregnant patients, and is less
cumbersome to perform.5
Anesthetic management
Evaluation
Preoperative evaluation of parturients with CKD includes assessment of the changes characteristic of
chronic renal failure.34 CKD may affect other organ systems, either because of primary renal disease or secondary to other systemic diseases. It is therefore important
to identify any physiologic abnormalities in order to
optimize management. Many patients are hypertensive
and may have co-existing preeclampsia. Depending on
the severity and duration of the disease, some may be
at risk of left ventricular failure secondary to uid overload, co-existing anemia or uremic cardiomyopathy.26
The physiologic anemia of pregnancy is superimposed
on the anemia of CKD, and may require correction with
supplemental iron, erythropoietin or, if necessary, red
cell transfusion. The correction of altered volume and
electrolyte balance may require dialysis.
Patients with renal insufciency are at risk of abnormal bleeding. Clinical features include easy bruising,
bleeding from oral mucosa or gastrointestinal bleeding.
In addition, patients may bleed excessively from invasive
procedures. The primary cause is platelet dysfunction,
although the exact mechanism is unclear and there is
no clear correlation between the severity of renal failure
and bleeding. Proposed mechanisms include the presence of uremic toxins, anemia and enhanced nitric oxide
production in platelets and endothelial cells. Patients
who manifest bleeding can be treated in several ways.
Dialysis reduces bleeding in the majority of patients.
Heparin-free hemodialysis or peritoneal dialysis is recommended if there is active bleeding. Arginine vasopressin (DDAVP) releases von Willebrand factor and can be
administered intravenously or subcutaneously. The normal dose is 0.3 mg, given over 30 min. The effects are
evident in 1 h and last for 8 h. Tachyphylaxis occurs
as the stores of von Willebrand factor are depleted. Severe anemia should be treated. Further management options include cryoprecipitate or estrogen.35
Premedication
Before elective operative procedures, parturients must
be fasted as per standard guidelines. There may be delayed gastric emptying and hyperacidity secondary to
underlying renal disease (e.g. diabetes) or uncorrected
uremia, increasing the risk of aspiration pneumonitis.
228
In addition to sodium citrate, a histamine H2-receptor
antagonist such as ranitidine and metoclopramide may
be given when time allows. The recommended single
doses for patients with renal failure are ranitidine
50 mg and metoclopramide 10 mg intravenously.34
Monitoring
The choice of hemodynamic monitoring should be individualized. Standard non-invasive monitoring (pulse
oximetry, non-invasive blood pressure, and electrocardiogram) may be sufcient when parturients present
with early stage renal dysfunction and well-controlled
hypertension for uncomplicated vaginal or cesarean
delivery. S-T segment monitoring may be useful in parturients at risk of co-existing coronary disease. It is
important to protect existing arteriovenous stulas with
appropriate positioning and padding of the limb. Intravenous access and non-invasive blood pressure monitoring should be avoided in that arm. The use of invasive
hemodynamic monitoring may be necessary in parturients with severe end-organ disease, uncontrolled hypertension, or rapidly uctuating volume status.
Neuromuscular and temperature monitoring are indicated with general anesthesia, particularly if they have
received neuromuscular blockers in combination with
magnesium sulfate.
Renal protection
Various regimens, such as low-dose dopamine or dopexamine infusions, or diuretics have been used in attempts
to protect the kidneys in the intra- and postoperative
periods. A recent systematic review concluded that there
is no evidence to suggest that any measures used for renal protection during the perioperative period, including
dopamine and its analogues, diuretics, calcium-channel
blockers, angiotensin-converting-enzyme inhibitors or
hydration uids, are benecial.33 Many of these interventions are contraindicated in the parturient due to adverse fetal effects. Therefore, standard therapy, aimed at
maintaining tissue oxygenation and perfusion should be
used.36 In patients with residual kidney function, drugs
known to be nephrotoxic, such as aminoglycosides and
non-steroidal anti-inammatory drugs, should be
avoided.
General anesthesia
Anesthetic management is inuenced by the extent of renal dysfunction and hypertension. Parturients with stable renal disease, mild-to-moderate renal insufciency,
well-controlled hypertension and who are euvolemic
do not require special preparations. In contrast, parturients on dialysis with end-stage renal disease, and
poorly-controlled hypertension present many anesthetic
challenges.
Inhalational anesthetics cause a transient, reversible
depression in renal function. Renal blood ow is
Neuraxial anesthesia
Neuraxial anesthesia appears to be a safe anesthetic option. In general, chronic renal failure causes an increase
in coagulation factors and may increase the risk of
thrombosis. However, as renal function and the accompanying anemia worsens, impaired release of tissue plasminogen activator, elevated plasminogen and D-dimer
and other factors may cause platelet dysfunction.41
There are case reports of neuraxial hematoma associated with chronic renal failure, however there is insufcient information to determine the exact cause.42,43
Severe anemia may be contributory. In addition, the effects of low-molecular-weight heparin may be prolonged.44 Global clotting function has been assessed
using thromboelastography in parturients with thrombocytopenia.45 In combination with other tests of coagulation, normal thromboelastographic parameters may
be reassuring. In parturients with severe renal compromise, it may be prudent to monitor neurologic function
below the block more frequently than in normal patients. New onset of low back pain with acute motor
and sensory decits in the lower extremities may suggest
the development of epidural hematoma. The use of dilute local anesthetic solutions in combination with opioid spinal analgesics permits immediate evaluation of
neurologic status, which may permit early diagnosis of
an epidural hematoma.26
Women who require dialysis have special requirements. Patients on intermittent hemodialysis may have
residual circulating heparin that precludes regional anesthesia. Their intravascular volume may uctuate between treatments, and it is important to determine
volume status before considering regional anesthesia.
Useful signs may include current weight compared to
V. Chinnappa et al.
dry weight, heart rate and blood pressure (and particularly how it changes with posture). If the patient is euvolemic before initiating the block, it may be prudent to
treat hypotension with a vasopressor rather than uids
to reduce the chances of circulatory overload and pulmonary edema. Hypovolemia and co-existing uremic
autonomic neuropathy may lead to profound hypotension during the initiation of sympathetic blockade, a risk
which may be minimized using slow induction of epidural anesthesia.
Reports on the efcacy and pharmacokinetics of local
anesthetics in uremic patients have been controversial.
There are reports of systemic local anesthetic toxicity
after bupivacaine brachial plexus blockade in patients
with chronic renal failure.46,47 However, Rice et al.
found no signicant difference in the pharmacokinetic
prole of bupivacaine after brachial plexus blockade in
uremic and normal healthy patients.48 The pharmacokinetics of ropivacaine are not affected by renal failure.49
Summary
Parturients with renal insufciency or failure present a
signicant challenge for the anesthesiologist. Close communication amongst medical specialists, including nephrologists,
obstetricians,
neonatologists
and
anesthesiologists is required to ensure the safety of the
mother and child. Pre-existing diseases should be optimized and close surveillance of maternal and fetal condition are indicated. Kidney function may deteriorate
during the pregnancy, necessitating early intervention.
The goal is to maintain hemodynamic and physiologic
stability while the demands of the pregnancy change.
Drugs that may adversely affect the fetus, are nephrotoxic or dependent on renal elimination should be
avoided.
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