1Department of Anaesthesia and Intensive Care, North Hampshire Hospital, Basingstoke, UK. 2Northern Schools of Anaesthesia Newcastle, Royal Victoria Infirmary, Newcastle upon Tyne, UK*Corresponding author. Present address: Department of Anaesthesia and Pain Management, Royal Perth Hospital, Perth 6000, Western Australia
Accepted for publication: October 22, 2001
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Abstract |
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Br J Anaesth 2002; 88: 4348
Keywords: complications, autonomic hyper-reflexia; complications, spinal cord injury; pharmacology, magnesium sulphate; intensive care
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Introduction |
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Case report |
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On presentation he had a Glasgow Coma Scale of 4, which improved to 9 with i.v. fluid resuscitation, a tympanic temperature of 38.2°C, a sinus tachycardia of 122 min1 and he was hypotensive (arterial pressure 75/32 mm Hg). He had a neutrophil leucocytosis (24.0x109 litre1), a C-reactive protein concentration of 270 mg litre1, a blood glucose concentration of 22.6 mmol litre1, and a base excess of 12. In addition, he was anuric with a serum creatinine concentration of 346 µmol litre1. An ultrasound scan revealed an absent right kidney, left hydronephrosis, and an empty bladder. A diagnosis of septic shock secondary to pyelonephritis was made and following blood culture the patient was commenced on cefotaxime 1 g three times daily, metronidazole 500 mg twice daily, and gentamicin 4 mg kg1, the dosing interval being dictated by daily serum gentamicin assays.
Intravenous fluid resuscitation was continued, the airway was secured by orotracheal intubation and artificial ventilation assisted using synchronized intermittent mandatory ventilation with pressure support. Continuous veno-venous haemofiltration was commenced and systolic arterial pressure was maintained above 100 mm Hg with i.v. fluid and norepinephrine 0.015 µg kg1 min1. Insulin was commenced at 4 units h1 to control blood glucose levels and sedation was maintained with propofol 180 mg h1 and fentanyl 100 µg h1. Once the patient was stable haemodynamically, a left-sided nephrostomy tube was inserted percutaneously under ultrasound guidance. Blood and urine cultures grew Enterococci and Proteus spp.
The patient made good progress and by the fourth day after admission no longer required vasopressor support and was polyuric through the nephrostomy. His white cell count and serum creatinine concentration had fallen to 9.0x109 litre1 and 215 µmol litre1, respectively. Continuous veno-venous haemofiltration was discontinued.
On the fifth day, the patient developed profuse diarrhoea. Shortly afterwards, unpredictable and sudden paroxysms of systemic hypertension started, the arterial blood pressure reaching 240/140 mm Hg on occasion. These episodes were associated with pallor and diaphoresis. The heart rate remained largely unchanged. Rising serum glucose levels were treated by adjusting the continuous i.v. infusion of insulin, which was increased from 4 to 8 units h1. A diagnosis of autonomic hyper-reflexia was made and sedation was increased such that the patient just coughed on suctioning. Nevertheless, paroxysms of hypertension increased in frequency and severity over the following 24 h. They were thought to be triggered by visceral stimulation associated with the diarrhoeal illness. A bolus dose of magnesium sulphate 5 g (approximately 40 mg kg1) was administered by slow i.v. injection over a 15-min period with continuous ECG and invasive arterial pressure monitoring. This was followed by an infusion of magnesium sulphate at 12 g h1 with the aim of achieving a plasma concentration of 24 mmol litre1.1 A decrease in both the frequency and severity of the systolic hypertensive episodes was noted almost immediately (Table 1).
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Discussion |
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Autonomic hyper-reflexia can be stimulated either by visceral or, less commonly, cutaneous stimuli below the level of the lesion. Patients with high spinal cord injury on intensive care units may be exposed to such stimuli. These include catheterization and distension of the urinary bladder, urinary tract infections, enemata, sigmoidoscopy, various causes of gastrointestinal distension, and manipulation of pressure sores.7
The pathophysiology of autonomic hyper-reflexia involves the loss of higher centre inhibition of sympathetic outflow. More importantly, however, it results from disorganized connections between pre-synaptic afferent terminal buttons (which multiply chaotically after cord injury) and interneurones within the spinal cord, which in turn synapse with sympathetic efferents.2 Patients with chronic injury to the spinal cord are also known to have decreased levels of circulating catecholamines and an increased sensitivity to norepinephrine.7 In addition, plasma norepinephrine levels rise markedly during episodes of autonomic hyper-reflexia.7
The management of autonomic hyper-reflexia requires removal of the precipitating stimulus when possible, and if necessary pharmacological intervention. In the intensive care unit it may not be possible easily to avoid, remove, or treat the precipitating stimulus, and pharmacological intervention then becomes necessary to prevent and treat life-threatening complications. Drug therapies include alpha-1 adrenoceptor blockers, beta-adrenoceptor blockers, calcium channel antagonists, alpha-2 adrenoceptor agonists, ganglion blockers, nitrates, hydralazine, and reserpine.2 6 7 8 Many of these drugs and also magnesium sulphate have played a part in the management of the paroxysms of systemic hypertension associated with tetanus and phaeochromocytoma.1 9 10
Magnesium controls catecholamine-induced hypertensive crises through several anti-adrenergic mechanisms of which calcium antagonism is of primary importance.11 Magnesium is an essential regulator of calcium movement in and out of the cell, and of the actions of calcium within the cell.12 In addition, magnesium competes with calcium for transmembrane channels. By these mechanisms, magnesium inhibits catecholamine release both from the adrenal medulla and from adrenergic nerve endings. Magnesium causes a reduction of systemic vascular resistance by a direct vasodilator effect on vessel walls and by direct blockade of catecholamine receptors.12 Magnesium possesses anti-arrhythmic properties, and offers protection from catecholamine-induced myocarditis by the preservation of intracellular adenosine triphosphate and glycogen stores and by reducing lactate production.1 9 1113 The serum concentration required to exert these effects is in the range of 24 mmol litre1.1
Although magnesium has a high therapeutic index, at plasma levels above 2.5 mmol litre1, it causes muscle weakness by the dose-dependent inhibition of acetylcholine release in peripheral nerves. Loss of tendon reflexes occurs at a plasma concentration above 5 mmol litre1 and respiratory depression above 7 mmol litre1.11 Muscle weakness from magnesium administration is thought to develop more rapidly if commenced in the presence of sedation.14 Small but significant reductions in pulmonary function have been reported in pre-eclamptic patients in labour receiving magnesium sulphate infusions, with plasma concentrations in the therapeutic range.15 Respiratory insufficiency is a common consequence of spinal cord injury and results mainly from muscle weakness, although there is some data to suggest that reductions in respiratory drive and ventilatory response to hypercapnia also occur.2 We therefore emphasize the ready availability of ventilatory support when administering large doses of magnesium sulphate to patients with high spinal cord injury.
Our patient was receiving ventilatory support and sedation throughout the administration of magnesium, and a decrease in minute ventilation only became apparent as the plasma level of magnesium approached the upper limit of the targeted range. The rapid rate of change of magnesium concentration was, however, probably due to the patients renal dysfunction. Frequent monitoring of plasma levels of magnesium is essential especially in the presence of renal dysfunction, and in view of the fact that clinical assessment of muscle weakness may prove impossible in sedated patients and in patients with chronic spinal cord injury.
In a recent case report, Maehama, Izena and Kanazawa describe the successful use of magnesium sulphate in the management of autonomic hyper-reflexia occurring during labour in a patient with high spinal cord injury.16 Our case report highlights this serious complication of spinal cord injury in the intensive care setting and introduces the use of magnesium sulphate for its management. In view of its pharmacological mode of action, its wide therapeutic index in the ventilated patient, and its successful use in the management of other systemic hypertensive crises mediated by the autonomic nervous system, we advocate further research into the use of magnesium sulphate in the treatment or prevention of autonomic hyper-reflexia secondary to chronic spinal cord injury in the intensive care unit.
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References |
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