Abstract
Magnesium sulfate administered as an intravenous infusion is considered safe. However, there have been concerns about the neuromuscular blocking properties of magnesium that can cause respiratory insufficiency. We report a patient with mild tetanus who, after being started on magnesium infusion, developed progressive respiratory insufficiency, proximal muscle weakness and ptosis. On discontinuation of magnesium infusion, the muscular weakness improved and respiration became normal. The safety of magnesium sulfate infusion for the management of tetanus needs to be re-evaluated.
Keywords
magnesium sulfate ; tetanus;
1. Introduction
Tetanus is prevalent in the developing world. Although mortality from tetanus has decreased significantly since the advent of critical care, no pharmacological intervention has been proven to arrest the progress of the disease. Clinicians can only rely on symptomatic and supportive therapy apart from specific antibiotics and immunoglobulins to contain the illness. Recently, there have been encouraging reports on the use of magnesium sulfate in the treatment of tetanus.
Magnesium was first used in the treatment of tetanus over 100 years ago.1 Since 1985, there have been various case reports2 and case series3−6 describing its use to control spasms, reduce rigidity and stabilize the sympathetic dysfunction from tetanus. Attygalle and Rodrigo,3,4 from Sri Lanka, suggested that magnesium could be used as the sole agent for the control of spasms in tetanus without the need for sedation and artificial ventilation. However, Thwaites and Farrar7 are sceptical about the benefits of magnesium as it also has properties of neuromuscular blockade. In a randomized controlled trial, Thwaites et al8 demonstrated that magnesium therapy did not decrease ventilatory requirement in severe forms of tetanus.
From the experience in our center, we are of the opinion that magnesium sulfate is not efficacious as a sole agent to control spasms and rigidity in severe tetanus, but it is efficacious in milder forms of tetanus with only rigidity or rigidity with mild spasms. Recently, we encountered a patient with mild tetanus who presented with trismus and rigidity. The patient developed generalized neuromuscular weakness after treatment with magnesium infusion for 24 hours. This case raises safety issues in the use of magnesium sulfate in tetanus.
2. Case Report
A 21-year-old male patient presented with symptoms of tetanus following an incision and drainage procedure for a pustule in the gluteal region. The procedure was done in a small local hospital. Fifteen days after the procedure, the patient developed inability to open his mouth fully and was not able to eat. On presentation to the emergency department, he was found to have trismus and mild rigidity of the abdomen and neck. As a diagnosis of tetanus was established, he was admitted to the Adult Tetanus Unit of our hospital.
Intramuscular human tetanus immunoglobulin 1500 U was administered, and metronidazole 500 mg injection every 8 hours was initiated. Since the patient had trismus and abdominal rigidity, he was graded to have Ablett Grade I disease,9 and magnesium sulfate infusion was started at 2 g per hour after an intravenous bolus of 70 mg/kg. At this juncture, the vital parameters were within normal limits, with a respiratory rate of 16−18 breaths/min. Blood samples were drawn for daily estimations of serum magnesium, and patellar reflex was monitored every 2 hours in accordance with the unit’s protocol.
On day 2 of admission, the patient was found to have an increased respiratory rate, varying from 28 breaths/min to 32 breaths/min. Ptosis was noted on the same day. The muscle power was 3/5 in all limbs; there was proximal muscle weakness but the deep tendon reflexes remained intact. Vital parameters like temperature, heart rate and blood pressure were all within normal limits. Pulse oximetry demonstrated a fall in oxygen saturation from 97− 98% to 92−93% when breathing room air. Oxygen therapy was instituted by ventimask. Serum potassium level was 3.8 mmol/L, sodium was 141 mmol/L, and ionized calcium was 1.1 mmol/L. Since the patient was receiving only metronidazole and magnesium (apart from nutritional supplements), we thought of the possibility of hypermagnesemia and therefore stopped the magnesium infusion immediately.
Baseline magnesium on the day of admission was 3.1 mg/dL (normal range, 1.8−3.0 mg/dL), while it was 6.3 mg/dL on day 2. Ptosis and muscle weakness gradually improved on day 3, and improvement was particularly remarkable on day 4, with muscle power of 4/5. He was discharged after a full recovery on day 6.
3. Discussion
The use of magnesium sulfate in tetanus has been described as early as 1900.1 Its intravenous infusion has been reported in the treatment of tetanus for the last two decades, signifying the efficacy and simplicity of this modality. Though there are concerns about its safety on account of its neuromuscular blocking properties, these concerns have not been supported by experience from case series or randomized clinical trials.
Magnesium acts as a presynaptic neuromuscular blocker.10 It antagonizes the calcium in the neuromuscular junction and myocardium. It also inhibits parathyroid hormone release which can lower calcium level. Yet, overdosage with magnesium can cause weakness and paralysis.11 Muscle weakness usually occurs at serum levels between 20 and 34 mg/dL.12 Therefore, the occurrence of muscle weakness well below this range and within the therapeutic range as in our case is unusual and, to the best of our knowledge, has never previously been reported in the literature. The cause of this unusual presentation is somewhat open to speculation. Nutritional deficiency of calcium (due to the patient’s poor socioeconomic status) or hypoparathyroidism are two possibilities that should be considered. The patient was put on calcium supplementation and his parathyroid hormone levels were found to be normal.
Curiously, there is a report of tetanus presenting with ptosis13 wherein the portal of entry was the oral cavity. However, in our case, the portal of entry was the gluteal region; hence, it was unlikely to cause cephalic tetanus with ptosis. Also, the onset and resolution of ptosis coincided with magnesium therapy.
Retrospectively, we feel that intense monitoring of neuromuscular function would have warned us of the onset of paresis earlier. But monitoring neuro muscular transmission for days in awake patients on magnesium sulfate infusion seems difficult. Proximal muscle weakness was present despite preserved deep tendon reflexes. It is important to note that patellar tendon reflex is widely considered to be a marker to titrate magnesium sulfate therapy in tetanus and eclampsia. It may be practical to suggest regular monitoring of the power of proximal muscle groups in addition to patellar tendon reflex in patients on continuous magnesium therapy.
In conclusion, our report highlights the need to re-evaluate the role of magnesium therapy in tetanus and calls for intense neurologic monitoring of patients on magnesium sulfate infusion.
Acknowledgments
We are grateful to the patient for granting us permission to publish this clinical experience of his case.