SICKLE cell disease is a group of hematologic disorders caused by a single base substitution of the β-globin subunit of hemoglobin. When deoxygenated, the affected erythrocytes can polymerize, metamorphosing from flexible nourishing cells to unyielding obstacles that occlude blood flow and result in tissue and nerve ischemia. Affecting 1 of every 600 African-Americans and a significant percentage of African, Mediterranean, and Indian individuals, sickle cell disease is the most common clinically significant hemoglobinopathy in the United States. 1We report a case of a lower extremity peripheral neuropathy induced by a sickle cell vasoocclusive crisis after spinal anesthesia for cesarean delivery.
A 25-yr-old African-American, primaparous woman with a 31-week breech presentation, singleton gestation, was admitted for premature rupture of membranes, chorioamnionitis, and severe oligohydramnios. Past medical history was notable for severe sickle cell disease (Hemoglobin SS ), which in the previous 2 yr had required a permanent portacath placement and frequent hospital admissions for management; two months previous, the patient had been admitted for pneumonia and management of a vasoocclusive crisis. With the decision for a cesarean delivery and the administration of antibiotics, the patient was taken to the operating room and placed in the right lateral decubitus position. Following the placement of standard monitoring, an intravenous lactated Ringers bolus and aseptic preparation, a spinal anesthetic (12 mg hyperbaric bupivacaine, 0.75%, with 10 μg fentanyl), was placed on the first attempt with a 25-gauge Whitacre needle at the L3–L4 interspace. The patient was placed supine with a left lateral tilt and the delivery proceeded uneventfully with no hemodynamic, anesthetic or obstetric complications.
Postoperatively, the spinal blockade underwent an expected sensory and motor resolution. A single dose of 30 mg intramuscular ketorolac was given to alleviate mild abdominal and bilateral shoulder discomfort, and the patient was started on a hydromorphone patient controlled intravenous analgesia pump. On the morning of postoperative day 1, the patient reported weakness, numbness, and tingling of the lower left extremity, a location consistent with previous vasoocclusive pain crises. On examination, decreased deep tendon reflexes (1/2), and diminished strength and sensation of the affected limb consistent with a L3–L5 plexopathy was noted. The lower right extremity had a normal examination, and neither back discomfort nor bladder and bowel involvement was observed. Conservative therapy with fluids, oxygen by nasal cannula, and additional pain relief were administered, and a slight improvement in symptoms was noted by that evening.
On postoperative day 2, the patient awoke with significant dyspnea, pleuritic chest pain, and severe discomfort of the upper and lower back, shoulders, and the lower left extremity. On examination, fine inspiratory and expiratory crackles, tachypnea and tachycardia, but a stable blood pressure, were observed. Although consistent with a sickle crisis, the symptoms were also suggestive of a pulmonary embolus. A ventilation–perfusion scan indicated a greater than 50% likelihood of a pulmonary embolus; however, as anticoagulation was being discussed with hematology consultants, the patient’s clinical condition progressed to include bilateral motor and sensory deficits in a T11–S2 distribution with diminished bowel and bladder control. While urgent neurology consultation was obtained, magnetic resonance imaging of the lumbosacral spine was performed that demonstrated no evidence of an epidural hematoma. Despite negative lower extremity noninvasive studies and the inability to confirm the diagnosis of a pulmonary embolus with a pulmonary arteriogram because of the patient’s refusal of the procedure, empiric therapy with intravenous heparin and oral enoxaparin was started. Significant interval improvement occurred in the pulmonary and lower extremity symptoms and the patient was discharged on postoperative day 9, with complete motor, bladder and bowel recovery, and a mild sensory deficit of the lateral aspect of the left heel.
The ability to polymerize when deoxygenated is unique to sickle hemoglobin and responsible for the cellular injury observed with the disease. A disease with variable expression, the symptoms of sickle disease are modified by several factors, the most influential being genotype, of which the homogenous SS disease has the most significant morbidity and mortality. 2Although no single mechanism is responsible for vasoocclusion, the leading catalyst is believed to be the cellular efflux of potassium induced by deoxygenation, which in turn produces an increase in the density and tendency of sickle cells to interact with each other, endothelial cells, and plasma constituents. 3These adhesive interactions often lead to endothelial cell damage and vasoconstriction, and ultimately culminate in acute, sometimes fatal, episodes of vasoocclusion. 4While neurologic sequelae frequently occur, they are principally confined to the brain and its circulation 4; only rarely are the spinal cord or peripheral nerves involved.
In our case, sickle cell disease complicated the diagnosis of progressive neurologic symptoms. Although the unilateral deficit was initially similar in expression and distribution as previous sickle occlusion attacks, the recent postpartum status mandated additional considerations, including alterations because of pregnancy, as well as obstetric and anesthetic complications. Pregnancy and delivery per se are commonly associated with neurologic injuries; 1 in 2,600–6,400 deliveries is affected in such a manner. 5Frequently unilateral, these postpartum injuries are usually preceded by prepartum or intrapartum neurologic symptoms, prolonged labors, or instrumental deliveries. 5Spinal anesthesia, which can also be unilateral in distribution and recovery, is rarely associated with significant or persistent neurologic injuries 5; when they do occur, some indication is usually noted during the placement of the technique. In prospectively investigating 40,640 spinal anesthetics, Auroy et al. 6noted only 24 cases of neurologic injury (19 radiculopathy, 5 cauda equina syndrome), of which two thirds experienced pain on needle insertion or local anesthetic injection. Although transient neurologic syndromes occur with modest frequency, including in patients undergoing cesarean delivery, the classic symptoms of low back pain and or dysesthesia with radiation to the buttocks, thighs, or legs were not consistent with our case. As our patient experienced an uncomplicated cesarean delivery without prolonged retractor use or a preceding labor, and an equally uncomplicated placement and hemodynamic sequlae from a spinal anesthetic, the influence of the pregnancy, as well as obstetric and anesthetic complications, as the etiology for the deficit was less compelling. While sickle cell–induced peripheral neuropathies are usually bilateral, unilateral symptoms have been reported, 7as with our patient just 2 months previously.
Although symptomatic improvement after therapy directed towards a sickle cell occlusive crisis was initially observed, the acute onset and progression of clinical signs suggestive of a pulmonary embolus and a possible epidural or spinal hematoma prompted additional diagnostic and treatment considerations. The diagnoses of pulmonary emboli and central neuraxial hematomas have distinct and dichotomous therapeutic goals. Although thrombolytic and fibrinolytic agents are the recommended treatment for pulmonary emboli, the use of such therapies has the potential to cause or extend hematomas. With a ventilation–perfusion scan indicative of a pulmonary embolus and a magnetic resonance imaging scan negative for a hematoma, thrombolytic therapy was commenced, and an almost complete resolution of symptoms occurred. Although the treatment of sickle cell disorders does not routinely include anticoagulants, recent evidence strongly supports the inhibition of sickle erythrocyte adhesion to the endothelium by heparin 8; moreover, in the setting of sickle cell–induced cerebral thrombosis, the use of heparin has been recommended. 9Of interest, although epidural analgesia has been promoted as a method to effectively treat sickle cell crises unresponsive to conventional management, 10we chose to avoid this option because of the administration of anticoagulants and the potential to obscure signs of neuropathy progression or regression.
Despite the favorable outcome in our patient, this case underscores the need to consider the independent influences of pregnancy, labor and delivery, obstetric and anesthetic interventions, as well as the established comorbid conditions when presented with a peripheral neuropathy in a patient with sickle cell disease.