1 University Department of Anaesthesia and Intensive Care and 2 Department of Neurosurgery, University Hospital and City Hospital, Nottingham, UK
Corresponding author. E-mail: ravi.mahajan@nottingham.ac.uk
Accepted for publication: April 10, 2003
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Abstract |
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Methods. Fifteen healthy volunteers were recruited. Using transcranial Doppler ultrasonography, Vmca was recorded continuously. The strength of autoregulation was assessed by the transient hyperaemic response test, and the CRCO2 was measured by assessing changes in Vmca to the induced changes in end-tidal carbon dioxide. I.V. infusion of magnesium sulphate was then started (loading dose of 16 mmol followed by an infusion at the rate of 2.7 mmol h1) for 45 min. The cerebral haemodynamic variables were measured again near the end of the infusion of magnesium sulphate.
Results. Total serum magnesium levels were doubled by the infusion regimen. However, there were no significant changes in Vmca, strength of autoregulation, or CRCO2. Five of the volunteers reported marked nausea and two developed significant hypotension during the loading dose.
Conclusions. Infusion of magnesium sulphate, in a dose that doubles its concentration in plasma, does not affect Vmca, strength of autoregulation or CRCO2 in healthy volunteers. However, it can be associated with nausea and hypotension.
Br J Anaesth 2003; 91: 2735
Keywords: blood, haemodynamics; brain, cerebral circulation; ions, magnesium sulphate; measurement techniques, transcranial Doppler ultrasonography
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Introduction |
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Magnesium may dilate cerebral vessels, and thus be responsible for relieving vasospasm in patients with pre-eclampsia.5 Its effects on other aspects of cerebral haemodynamics, such as autoregulation to the changes in perfusion pressure (cerebral autoregulation) and cerebral vascular reactivity to carbon dioxide (CRCO2), are not well documented, in health or in disease. This knowledge is important for its judicious use, particularly in view of potential increase in its clinical applications in neurological diseases. In the present study, using transcranial Doppler (TCD) ultrasonography, we evaluated the effects of a clinically relevant dose of magnesium sulphate on middle cerebral artery (MCA) flow velocity (FV), cerebral autoregulation, and CRCO2 in healthy volunteers.
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Methods and results |
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All subjects were studied in the supine position with the head resting on a pillow. The left MCA was insonated through the temporal window using a 2 MHz TCD ultrasound probe (SciMed QVL 120, SciMed, Bristol, UK). The depth of insonation was adjusted to achieve maximal signal. The position of the probe was fixed using a headband. The FV was recorded continuously on digital audiotape for subsequent analysis using specific software (SciMed, Bristol, UK). I.V. access was secured and monitoring was initiated using an electrocardiogram, non-invasive arterial pressure measurement and pulse oximetry (Marquette Tramscope: Marquette Electronics, Milwaukee, WI, USA). Mean arterial pressure (MAP) was measured at 2-min intervals and the partial pressure of end-tidal carbon dioxide (E'CO2) was measured continuously using a nose-clip and mouthpiece (Marquette Tramscope: Marquette Electronics).
After an initial period of rest of approximately 10 min, cerebral haemodynamic variables such as Vmca, cerebral autoregulation, and CRCO2 were measured in each subject. Venous blood samples were taken for measurement of serum magnesium levels. I.V. infusion of magnesium sulphate was then started. The regimen for the infusion was a loading dose of 16 mmol magnesium over 15 min, followed by an infusion of magnesium at 2.7 mmol h1 for 45 min.6 Nearing the end of the infusion, measurements of cerebral haemodynamic variables and serum magnesium were repeated.
Cerebral autoregulation was assessed using the transient hyperaemic response (THR) test. The test involves establishing continuous measurement of Vmca, and then compressing the ipsilateral common carotid artery for 10 s. The Vmca decreases suddenly at the onset of compression and, if autoregulation is intact, shows a hyperaemic response at the release of compression.79 The criteria for accepting a THR test and methods of processing the TCD data have been described previously.79 For analysis, the Vmca waveform immediately before the compression (F1), the first waveform immediately following compression (F2), and that immediately after release (F3), were selected. The time-averaged mean of the outer envelope of the FV was used. Two indices of cerebral autoregulation, the transient hyperaemic response ratio (THRR) and the strength of autoregulation (SA) were calculated:79
THRR=F3/F1(1)
SA=(F3 · P2)/(MAP · F1)(2)
P2 is the estimated pressure in the MCA at the onset of compression and the greater of 60 mm Hg (the assumed lower limit of autoregulation), or the values derived from equation 3.
P2=MAP · F2/F1(3)
For the assessment of CRCO2, hypo- and hypercapnia were induced and changes in Vmca were recorded. For hypocapnia, volunteers were instructed to hyperventilate, by increasing the depth and the rate of breathing, gradually to achieve a 1 kPa decrease in E'CO2. For hypercapnia, carbon dioxide was added to the inspired gases (oxygen enriched air; inspired concentration of oxygen <25%) in increments to achieve a 1 kPa increase in E'CO2. CRCO2 was expressed as percent change in Vmca per kPa change in E'CO2.
Data pooled from our previous work,79 indicate that the mean (SD) value for the THRR is 1.36 (0.09), and that for the SA is 0.98 (0.09) under normal physiological conditions. A change of more than 2 SD (equivalent to the change induced by 1 kPa change in carbon dioxide7) was considered significant. We calculated that 15 subjects would be required to reject the null hypothesis for a more than 2 SD change in the value of SA or THRR at a significance level of <0.01 with the power (1ß)>0.90. The data were analysed using paired Students t-tests.
All volunteers reported a generalized feeling of warmth and slight aching at the site of infusion. During the loading dose, five of the volunteers reported nausea, and two of them suffered retching; these symptoms resolved spontaneously without requiring any intervention. Two volunteers developed transient hypotension (>25% decrease in the MAP from baseline) towards the end of the loading dose. This required temporarily stopping the infusion (for 23 min) and then restarting once the arterial pressure recovered to normal. In both of these volunteers, the arterial pressure recovered within 2 min. None of the volunteers developed any dysrrhythmia.
Table 1 summarizes the results. The infusion regimen almost doubled the levels of magnesium in the plasma. There were no significant changes in MAP or E'CO2. Also, Vmca, THRR, SA, and CRCO2 remained unchanged.
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Comment |
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The effects of magnesium on cerebral vessels remains undefined, although it is suggested to have a vasodilatory effect and to relieve vasospasm in pre-eclamptic patients.5 In a study by Belfort et al., infusion of magnesium did not have significant effects on MAP or Vmca in pre-eclamptic patients.10 In a recent study in patients with subarachnoid haemorrhage, infusion of magnesium did not change Vmca significantly.4 Our results in healthy volunteers are in agreement with these reports. In addition, we have shown that cerebral autoregulation and CRCO2 also remain unchanged.
The dose regimen of magnesium infusion used in this study has been shown previously to increase serum magnesium concentration rapidly to double the physiological level.6 This regimen is likely to be adopted for the forthcoming clinical trials of magnesium in stroke.6 Its lack of significant effects on cerebral autoregulation and CRCO2 would suggest that, in patients receiving magnesium, the unaffected parts of the brain would tend to retain the capacity to autoregulate the blood flow. Our results, however, cannot be extrapolated to the injured or affected parts of the brain.
During the course of the study several unexpected adverse events occurred. This is contrary to previous studies, which have shown magnesium to be generally free from troublesome side effects.46 Two of our volunteers developed hypotension toward the end of the loading dose. This required the loading dose to be stopped temporarily. The arterial pressure, in both these volunteers, recovered within 2 min of stopping the loading dose. Five of the volunteers reported marked nausea during the loading dose, two of whom also suffered retching. We were surprised by the unexpected higher incidence of side effects in this study compared with earlier reports.46 We postulate that this may be a result of the rate of change in serum magnesium concentration rather than the absolute level, as all these side-effects began within 4 min of commencing, and abated within 2 min of completing, the loading dose. Maybe the loading dose should be given over a longer period of time to prevent the adverse events.
In conclusion, in healthy volunteers, i.v. infusion of magnesium does not affect Vmca, cerebral autoregulation, or CRCO2, but can be associated with nausea and hypotension.
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Acknowledgements |
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References |
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