Anesthetic management for parturients with neurological disorders.

Anesthesia care for the pregnant and the parturient presenting with a neurological disease requires (1) expertise with neuroanesthesia and obstetric anesthesia care, (2) accurate physical examination of the neurological system preoperatively, (3) safe choice and conductance of the anesthesia technique (mostly regional anesthesia), (4) avoidance of unfavorable drug effects for the fetus and the nervous system of the mother, and (5) intraoperative neuromonitoring together with the control of the fetal heart rate. The most important message is that in the ideal case, any woman with a known, preexisting neurological disorder should discuss her plans to become pregnant with her physician before she becomes pregnant. Neurological diseases in pregnancy can be classified into three categories: (a) Pre-existent chronic neurological diseases such as epilepsy and multiple sclerosis (MS). (b) Diseases with onset predominantly in pregnancy such as some brain tumors or cerebrovascular events. (c) Pregnancy-induced conditions such as eclampsia and Hemolysis elevated liver enzymes and low platelets syndrome. This article addresses specific issues surrounding neurologic disease in pregnant women including MS parturient, spinal cord injury, parturient with increased intracranial pressure and shunts, parturient with brain tumors, Guillain-Barré syndrome and epilepsy.

INTRODUCTION

Therapeutic options for neurologic disorders have grown immensely over the past decade. As a consequence, when a woman becomes pregnant, the question is no longer whether to continue or discontinue her treatments; rather, the issues are which treatments to continue and how they should be administered. The most important message is that in the ideal case, any woman with a known, preexisting medical condition—neurologic or otherwise—should discuss her plans to become pregnant with her physician before she becomes pregnant.[1] Neurological diseases in Pregnancy can be classified into 3 categories:

Pre-existent chronic neurological diseases such as epilepsy and multiple sclerosis.

Diseases with onset predominantly in pregnancy such as some brain tumors or cerebrovascular events.

Pregnancy induced conditions such as eclampsia and HELLP syndrome.[2]

MULTIPLE SCLEROSIS

Definition and pathophysiology of MS

MS is a disease of young adults that may occur in pregnant women. The disease is characterized by chronic inflammation, demyelination, and gliosis in the central nervous system. The disease is most commonly acquired in young adults, with 3:2 of females to males. Characteristic abnormalities include increased immunoglobulin (Ig) G in the [cerebrospinal fluid (cerebrospinal fluid [CSF])], multifocal abnormalities on magnetic resonance imaging (MRI) of the brain and spinal cord. During 2009, a new theory on the possible cause of MS was reported by Dr Paolo Zamboni. Chronic cerebrospinal venous insufficiency is described as a chronic problem, where blood from brain and spine has trouble getting back to the heart. It is caused by a stenosis in veins that drains the brain and the spine. Blood can reflux back causing edema and leakage of red blood cells and fluids into the brain and spine. This (“slowed perfusion”) results in brain hypoxia. Iron from blood deposited in the brain tissue and crossing the brain-blood barrier.[3]

Symptoms of multiple sclerosis?[4]

Visual symptoms as optic neuritis, diplopia, and nystagmus.

Motor symptoms including paresis, plegia, and muscle atrophy.

Sensory symptoms including paresthesia, anesthesia, neuralgia, and neurogenic pain.

Coordination and balance symptoms: Ataxia, tremor, and vertigo.

Cognitive symptoms: Depression, dementia, and anxiety.

Other symptoms may include fatigue, gastroesophageal reflux, sleeping disorders, ataxia, tremor, and vertigo.

Treatment modalities for MS include the following drugs:

Immunomodulator: Type I interferon (IFN); anti-inflammatory cytokine.

Immunosuppressor: Chemotherapy agents: Azathioprine, cyclophosphamide, cyclosporine.

Corticosteroids and ACTH: Hydrocortisone, Dexamethasone.

Pain/Altered Sensation: Carbamazepine, Gabapentin.

Antidepressants and anxiolytics.

Anti-spasticity: Dantrolene.

Experimental medications: Monoclonal antibody.

Intravenous immunoglobulin to prevent postpartum relapse.

Interaction of MS and pregnancy

Effect of MS on pregnancy

The study of Dahl et al.,[5] reported that rates of infant mortality, congenital anomalies, and cesarean deliveries were also similar to those of the general population. The data also suggested an effect on deliveries. Although the number of planned cesarean deliveries increased, women delivering vaginally had an increased incidence of slow labor progression necessitating interventions. This result may have been partly due to perineal weakness and spasticity and fatigue related to MS.

Effect of pregnancy on MS

Pregnancy does not negatively affect prognosis of MS. Patients with exacerbating-remitting MS experience a slightly decreased rate of relapse during pregnancy and increased rate of exacerbations postpartum. The Pregnancy in Multiple Sclerosis (PRIMS) study was the first multicenter prospective study of MS in pregnant women, and it is the largest natural history study of pregnant women to date.[67] The relapse rate declined by approximately 70% during the third trimester of pregnancy compared with the rate observed in the year before conception. In the PRIMS study, the relapse rate increased by approximately 70% in the postpartum period and then returned to the prepregnancy rate.

Neither breastfeeding nor epidural analgesia affected the rate of relapse or progression of disability.[8] Women should be reassured that pregnancy does not appear to worsen long-term progression of MS.

How best to treat pregnant women with MS remains controversial. Although some claim that the suppression of MS during pregnancy is more potent than that achieved with currently available therapies for the disease.[9]

Possible postpartum treatments

There is some evidence to suggest that corticosteroids and intravenous Ig might be beneficial in the postpartum management of MS. Relapse rates also decreased in patients treated with intravenous (IV) (Ig) only after delivery (0.58) as compared with untreated patients (1.33). No significant adverse events were associated with IV Ig treatment in patients or newborns.[10]

Has[11] reported that the exacerbation rate after delivery in IV Ig-treated individuals was reduced by 33%. IV (Ig) was administered within 3 days after delivery and then monthly to patients thought to be at high risk for exacerbations.[11]

To summarize, apart from methotrexate and cyclophosphamide, most drugs used to treat MS can safely be used by pregnant women. IV steroids may be used safely during pregnancy, while IFN-β-1a and IFN-β-1b should be discontinued before pregnancy.[12]

Anesthesia at delivery

The use of analgesia during delivery for patients with MS has not been extensively evaluated, but there is no substantial evidence to suggest an increased risk of relapse. Anesthetic implications of multiple sclerosis is shown in Table 1. For “the patients with preexisting neurologic deficits,” American Society of Regional Anesthesia and Pain Medicine guidelines stated that these patients “may be at increased risk of new or worsening injury regardless of anesthetic technique” and “a careful risk-to-benefit assessment of regional anesthesia to alternative perioperative anesthesia and analgesia techniques should be considered.[13]

Table 1

Anesthetic implications of multiple sclerosis[12]

Neuraxial anesthesia and multiple sclerosis

A partial conduction blockade in the demyelinated areas is responsible for the “negative” symptoms associated with MS, such as weakness and hypoesthesia. Ectopic impulses at the site of demyelination are responsible for positive symptoms; seizures and spasticity. This pathophysiology raises important questions regarding the neuraxial anesthesia in MS patients.

First, we have to understand what are the effects of local anesthetics on demyelinated fibers?

Indirect evidence suggests that intravenous local anesthetic may unmask silent demyelination and aggravates negative symptoms of MS by increasing the conduction blockade. Intrathecal local anesthetic LA for spinal anesthesia was reported to unmask silent demyelination. But these symptoms are transient and reversible.[14]

A survey of UK experience suggested that most UK anesthetists would perform regional blocks for labor and cesarean section in MS, although their experience is limited. Many emphasized the need for thorough preassessment and informed consent. For most patients, diagnosis of MS should not be a contraindication for either epidural or spinal anesthesia.[15]

Few studies reviewed general anesthesia for MS, one of them used propofol, fentanyl, sevoflurane, N2O, and vecuronium. They concluded sevoflurane does not exacerbate symptoms, It also facilitates early postoperative neurologic assessment and it is one of ideal anesthetics for MS patients.[16]

Kulkami et al.,[12] and Sahin et al.,[17] reported two cases of MS patient who received desflurane for orthopedic surgeries. They believe that general anesthesia has less risk of complications than regional methods in MS patients and desflurane is a safe agent to use in these patients.

From previous studies, we may conclude that spinal, epidural, and general anesthesia can all be used safely in MS patients.

GUILLAIN-BARRÉ SYNDROME

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP, Guillain-Barré syndrome) has been linked to a variety of infectious agents. It typically begins within 30 days of an infection with progressive ascending weakness and gradual loss of deep tendon reflexes and sensory loss. AIDP neither appear to occur with increased frequency during pregnancy nor has uncomplicated disease been shown to affect pregnancy, labor, or delivery.[18] There is one case report of congenital Guillain-Barré syndrome in the neonate of an affected mother.[19]

Treatment in nongravid adults may involve plasma exchange or intravenous immune globulin. Neither treatment has been studied in pregnant women with AIDP, although aggressive fluid loading prior to plasma exchange may help to avoid hypotension. Maternal AIDP is not an indication for cesarean delivery, which should be reserved for the usual obstetric indications only. Consultation with the anesthesia service is important as these patients have some additional anesthetic issues (e.g., need to avoid succinylcholine, concerns about exacerbation of neurologic deficit, autonomic instability).[18]

SPINAL CORD INJURED

There are increasing numbers of women with spinal cord injured (SCI) who become pregnant and have healthy babies. However, women with SCI are at high risk of developing uncontrolled autonomic dysreflexia (AD) during labor and delivery [Table 2].

Table 2

Signs and symptoms of autonomic dysreflexia in patients with spinal cord injuries[20]

AD is a well-known clinical emergency in individuals who have suffered a SCI. It especially occurs in individuals with an injury at level T6 or above. An episode of AD is characterized by the acute elevation of arterial blood pressure (BP) and bradycardia, although tachycardia also may occur. Objectively, an increase in systolic BP greater than 20-30 mmHg is considered a dysreflexic episode. AD can present with a variety of symptoms and can vary in intensity from asymptomatic, to mild discomfort and headache, to a life-threatening emergency, such as when systolic BP climbs to 300 mmHg.[20]

In an acute episode, pharmacological agents are required, and nifedipine, nitrates, and captopril are the most commonly used and recommended agents. Magnesium sulfate has beneficial effect on autonomic hyperreflexia (AH) during labor in a patient with SCI. However, only nifedipine is supported by controlled trials (level 2).

With vaginal delivery or when cesarean delivery or instrumental delivery is indicated, adequate anesthesia (spinal or epidural if possible) is needed.

Epidural anesthesia: Is not contraindicated in SCI patients but it's less reliable with 18% failure rate epidural anesthesia is useful for the amelioration of AH.

Spinal anesthesia: May be superior to epidural for providing hemodynamic protection against AD during cesarean section.[21]

In the acute phase of new neurologic injury, general anesthesia may be the technique of choice to prevent further hemodynamic and respiratory deterioration. After the acute phase, current evidence is mostly reassuring with respect to the risks of neuraxial blocks as they may even be recommendable in some conditions. Most patients may benefit more from spinal techniques rather than from less reliable epidural ones. High concentrations and volumes of local anesthetics should be avoided at all times, especially in patients with nerve compression, large disc herniation, or spinal stenosis.[2223]

CEREBROVASCULAR DISEASE

Diagnosis of pregnancy-related stroke and cerebral venous thrombosis

Brain imaging is essential in order to determine whether a pregnant woman has suffered an intracerebral hemorrhage. Brain MRI and magnetic resonance venogram are generally considered the gold standard for the diagnosis of ischemic stroke and cerebral venous thrombosis, respectively.

The timing of scans may depend on the stage of pregnancy and the risk-benefit ratio of performing these scans. The risk from MRI is generally considered lower after the first trimester, and the risks with administration of gadolinium are still under debate.

Stroke prevention during pregnancy

Strategies to prevent stroke during pregnancy in high-risk women mimic those used for thromboprophylaxis, which include either unfractionated or low-molecular-weight heparin to 13 weeks’ gestation, followed by warfarin until the middle of the third trimester, then heparin until delivery and warfarin for 6 weeks postpartum.[24]

There are no randomized controlled trials (RCTs) of acute stroke treatment with thrombolysis or mechanical thrombectomy to guide decision-making in the pregnant population.[25]

The incidence of stroke during the childbearing ages alone is 10.7 cases per 100,000 women. However, evidence suggests that the postpartum period is associated with an increased risk of ischemic stroke. Ischemic strokes account for 85% of all strokes, while hemorrhagic stroke occurs in women at risk for intracerebral hemorrhage, in pregnancy due to eclampsia, vasculitis, or an aneurysm or vascular malformation. High BP is the most important risk factor for intracranial hemorrhage in pregnancy.[26]

STROKE AND PREGNANCY

Management of patients with pregnancy-related stroke is largely the same as that of no pregnant patients, with more consideration on maternal and fetal risks. Low-dose aspirin reduces the occurrence of perinatal deaths and preeclampsia in women with historical risk factors for preeclampsia [Tables 3 and 4]. Anticoagulation during pregnancy is indicated for current arterial or venous thromboembolism, prior venous thromboembolism on long-term anticoagulation, antiphospholipid syndrome with prior venous thromboembolism, and patients with a mechanical heart valve. Data from thrombolytic therapy for pregnant women with acute ischemic stroke are limited. It is critical that the risks and benefits of thrombolytic therapy for pregnant women and fetuses are considered cautiously.[27]

Table 3

Frequency of stroke associated with pregnancy[25]

Table 4

Incidence of pregnancy-related strokes: Comparison of published series[26]

INCREASED INTRACRANIAL PRESSURE

Idiopathic intracranial hypertension is a condition consisting of increased intracranial pressure of unknown etiology, predominantly affecting obese women of childbearing age. Symptomatic relief can be provided by lumbar puncture and withdrawal of CSF, and the technique has been described in laboring women using an intrathecal catheter. There are special considerations for anesthetic management in the parturient. Despite the presence of raised ICP in these patients, there are no specific contraindications to neuraxial techniques, and uncal herniation has not been reported to occur in patients with idiopathic intracranial hypertension (IIH).[28]

A combined spinal-epidural technique with a small volume of CSF withdrawal may provide labor analgesia and symptomatic relief in the parturient with idiopathic intracranial hypertension.[29]

ICP and regional anesthesia

Regional anesthesia may be appropriate to use when cesarean delivery is performed subsequent to recent successful and uncomplicated neurosurgery. The potential for a serious cerebral complication after dural puncture is of major concern if the ICP is high, because a rapid decrease in spinal CSF pressure may cause herniation or intracranial hemorrhage. Intracranial subdural hematoma formation after epidural anesthesia and subarachnoid hemorrhage (SAH) after spinal anesthesia have been reported several times in the literature and are thought to result from acute CSF pressure changes.[30]

Epidural injection can cause an increase in ICP by compression of the dural sac. The clinical significance of this increase has been questioned, but slow injection of incremental volumes of local anesthetic has been recommended.

Regional anesthesia (spinal or combined spinal epidural) has been successfully used for cesarean delivery in patients with paraplegia, AH, cervical arteriovenous malformation (AVM) and ventriculoperitoneal shunt (VPS). Epidural anesthesia has been used for cesarean delivery in patients with pseudotumor cerebri and a lumbar-peritoneal shunt in situ.[31]

CEREBRAL VASOSPASM

Cerebral vasospasm may complicate SAH 3-6 days after the initial bleeding. Although “Triple H-therapye” (hypertensive and hypervolemic hemodilution) is not based on high levels of evidence, it is applied in many centers. The pregnant woman has an increased plasma volume and to a lesser extent red cell mass, so is relatively hypervolemic and hemodiluted compared with the no pregnant state. In theory, these changes should be beneficial in the prevention of cerebral vasospasm after SAH.

Magnesium sulfate has been shown to reduce the severity of vasospasm after SAH and is the prophylaxis and treatment of choice in eclampsia, a condition associated with periods of cerebral vasoconstriction.

Nimodipine, which is commonly used to reduce the incidence of intracranial vasospasm, is potentially teratogenic. It may cause maternal hypotension and treatment of pregnant patients with SAH-induced vasospasm with nimodipine and “Triple-He” has not been reported.[32]

CESAREAN SECTION IN A PATIENT WITH VENTRICULOPERITONEAL SHUNT

The anesthetic approach of obstetric patients with VPS is complex, and the risk and benefits of anesthetic techniques, as well as the circumstances that led to this indication, should be considered at the time of the indication. Successful of neuroaxis block in patients with neurological diseases has been reported. As for VPS, formal contraindication for neuroaxis block does not exist in the literature. Cases should be individualized. In the present report, due to an obstetric emergency and the neurologic condition of the patient, a decision to use neuroaxis blockade was made. The technique provided adequate management of the airways, good maternal-fetal condition, and postoperative analgesia. The evolution was favorable and the patient did not show any neurologic changes secondary to the technique used.[33]

It is believed that pregnancy may be associated with shunt malfunction and the management of pregnant women with a malfunctioning ventriculoperitoneal shunt is a challenging medical condition for the anesthetist, the obstetrician, and the neurosurgeon.

Schiza et al.,[34] reported a case of malfunctioning ventriculoperitoneal shunt and she had a caesarean delivery under epidural anesthesia.

Hypertonic saline

Currently, mannitol is the recommended first choice for a hyperosmolar agent for use in patients with elevated ICP. Some authors have argued that hypertonic saline (HTS) might be a more effective agent; however, there is no consensus as to appropriate indications for use, the best concentration, and the best method of delivery. A meta-analysis of eight prospective RCTs showed a higher rate of treatment failure or insufficiency with mannitol or normal saline versus HTS.[3335] Another study also found that HTS is more effective than mannitol for the treatment of elevated ICP.[36]

Anesthesia for parturients with VPSs should consider risk versus benefits of anesthetic techniques. As for VPS. There is no contraindication for neuroaxial block in the literature.

Regional anesthesia (spinal or combined spinal-epidural) has been successfully used for CS in patients with cervical AVM and VPS shunt.

PARTURIENT WITH BRAIN TUMOR

Analgesia for labor and vaginal delivery

Pregnant patient with a brain neoplasm may be more prone to develop cerebral edema as a result of increase in ICP and compression of vital brain-stem. Sudden decrease in extracranial pressure leads to tentorial herniation through the foramen magnum. Also, since brain surgery may induce labor, cesarean section could be performed at any time with low morbidity/mortality and low blood loss in the case of worsening neurological status indicating progressing of the intracranial mass.

Choice of analgesia include: Subarachnoid block, epidural block, paracervical, bilateral lumbar sympathetic block, and pudendal block.

Epidural block: May cause inadvertent dural puncture, higher failure rate but greater volume of drug for satisfactory analgesia. Rapid epidural administration of large volumes of drug should be avoided to avoid increase in increased ICP.[3738]

Anesthesia for cesarean section

Most choose general endotracheal anesthesia, Thiopental induction, hyperventilation, and control of BP (nitroprusside, trimethasone). Although general anesthesia has the disadvantage of hypertension during intubation; thus, IV lidocaine and fentanyl may blunt cardiovascular response. Hypocapnia leads to uteroplacental insufficiency and No benefit for increased IICP.

In a recent study,[39] the baby was carried to full term and delivered via cesarean section under spinal anesthesia. Epidural anesthesia was an optimal choice because it allowed the maintenance of stable BP and neurological assessment of the patient during the section. General endotracheal anesthesia was readily available.

Ghaly et al., in 2012 presented an interesting case of parturient that underwent resection of a benign brain tumor 3 months ago and recovered with no new neurological deficits.

Since there was no postoperative MRI and the patient still had some neurological deficits, the anesthesia team decided to proceed with a general anesthetic using a rapid sequence induction and intubation. Postcesarean MRI revealed residual tumor compressing the brain stem and a loculated cyst. If a spinal subarachnoid blockade technique had been selected, the risk of uncal herniation, based on the postoperative MRI findings, may have been realized. They concluded the necessity of a comprehensive and thorough review prior to selecting the anesthetic approach to manage the patients with a history of brain tumor resection. Postoperative MRI should be performed to evaluate the extent of tumor resection and possible existence of residual tumor.[40]

ANESTHETIC MANAGEMENT OF PARTURIENT WITH EPILEPSY

Epilepsy is the most common neurological disorder. There are about 50 million people with epilepsy worldwide and half of them are women.

Effect of pregnancy on epilepsy

Pregnancy has variable effect on epilepsy. Seizures may decrease or remain unchanged in two thirds of patients according to European pregnancy registry of more than 1900 pregnancies. Risk of epilepsy is the highest during delivery.[41]

An evidence-based study published in 2009, recommended that women with epilepsy (WWE) should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high rate (84%-92%) of remaining seizure-free during pregnancy (level B).[42]

Effect of epilepsy on pregnancy

Population-based data from Norway indicate that WWE have increased risk of induction of labor and cesarean section. The risk was higher in women taking antiepileptic drugs (AEDs) than those not taking AEDs.[43]

WWE have a higher risk of preeclampsia, gestational hypertension, bleeding in pregnancy, and excessive bleeding postpartum.[44]

Anesthesia for delivery in epileptic patients

When the epileptic patient is well-controlled by therapy during pregnancy, it is not usually necessary a special treatment at the delivery. However, it is possible that the anesthesiologist is asked to treat epileptic symptoms occurring during labor. If no convulsions are present, a continuous epidural anesthesia throughout labor is preferred. This technique decreases seizure occurrence because (1) it suppresses labor pain, (2) maintains a constant anesthetic plasma concentration producing an anticonvulsant effect. It is important to do not overdosing local anesthetics: Bupivacaine 0.25%, 6 mL/h should be indicated.[45]

For patients in advanced labor or near delivery, propofol administration (1%, 3-4 mL in repeatable bolus) should be attempted. If this treatment is effective, the woman may have a normal delivery or a low forceps application with an acceptable level of consciousness. After delivery, diazepam 10 mg should be given.

For cesarean delivery, it is possible to control seizures by propofol and decide about general or spinal anesthesia after evaluating fetal conditions. In our experience, good results are achieved by spinal anesthesia. During surgery, a propofol infusion at rate 10-15 mL/h is administered. After delivery, diazepam 10 mg is usually given. Other drugs other than their routine therapy are not necessary by using this protocol. In any case, thiopental and general anesthesia may also be used with good results, the most known approach and the best one. An effective support is done by magnesium administration.[46]

That majority of seizures occurring in the perioperative period in patients with a preexisting seizure disorder are likely related to the patient's underlying condition and regional anesthesia in these patients is not contraindicated. Furthermore, because the likelihood of a postoperative seizure is increased in patients with a recent seizure, it is essential to be prepared to treat seizure activity, regardless of the anesthetic and analgesic technique.

Mostly, women can be administered lorazepam 4 mg intravenously if generalized seizures occur during labor. Magnesium sulfate is not an appropriate alternative for epileptic seizures. However, when seizures first present during the third trimester of pregnancy or the early postpartum period, it may be difficult to distinguish eclampsia from a new onset or late relapse of epilepsy. In these cases, treatment of eclampsia and evaluation of other etiologies for the seizure is warranted.[47]