Department of Anaesthesia, St Georges Hospital, Blackshaw Road, London SW17 0NE, UK *Corresponding author
Accepted for publication: June 17, 2002
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Abstract |
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Methods. Using a transcranial Doppler ultrasound, we measured the baseline mean and systolic cerebral blood flow velocity. Measurements were repeated following administration of diclofenac 75 mg i.v.
Results. There was no significant change in cerebral blood flow velocity. All other physiological variables remained constant.
Conclusion. Diclofenac does not cause a significant change in cerebral blood flow velocity in patients with supratentorial tumours.
Br J Anaesth 2002; 89: 7624
Keywords: analgesics, anti-inflammatory, non-steroidal, diclofenac; brain, cerebral blood flow; measurement techniques, transcranial Doppler
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Introduction |
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Methods and results |
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The study was performed in the anaesthetic room before induction of anaesthesia. Patients were not premedicated and were kept in the supine position throughout the study period, with the head resting on a pillow. I.V. and arterial cannulae were inserted under local anaesthesia. Monitors included ECG, continuous arterial pressure, arterial blood gas sampling and axillary temperature.
CBFV was monitored continuously on the ipsilateral side of the intracerebral pathology. The M1 segment of the middle cerebral artery was insonated through the temporal window using a 2 MHz transcranial Doppler (TCD) ultrasound probe (Pioneer EME TCD VER 2.10, Eden Medical Electronics, Überlingen, Germany). The TCD probe was fixed in position to maintain a constant angle of insonation throughout the study. Confirmation of the middle cerebral artery was achieved by increasing sonation depth to visualization of the bidirectional flow pattern typical of the bifurcation of the internal carotid artery to the middle cerebral and anterior cerebral arteries. Insonation depth was then decreased to the point of maximum signal intensity (4555 mm depth). The TCD frequency spectra, converted into flow velocity (cm s1), were calculated automatically by the TCD over 45 consecutive cardiac cycles.
Measurements of baseline mean and systolic CBFV were recorded, along with mean arterial pressure, heart rate, temperature, and arterial oxygen and carbon dioxide pressures. Diclofenac, 75 mg in 50 ml normal saline, was then infused over 15 min. The i.v. route was chosen to avoid first-pass metabolism and provide a reliable peak plasma concentration. All measurements were repeated at the end of the infusion (time 15 min) and after a further 25 min (time 40 min), to coincide with the time of peak plasma concentrations.
Anaesthesia was then commenced and surgery continued as normal.
Data are expressed as mean (SD). Data from previous studies indicate that the mean value for CBFV is 65.55 (4.2) cm s1 under normal physiological conditions.36 A change of >2 SD was considered significant and with a power of 0.8, =0.05 and ß=0.2, we calculated that eight subjects would be required.
Analysis of variance (ANOVA) for repeated measurements was used to compare the values. The changes from baseline to time 15 min and baseline to time 40 min following diclofenac administration were estimated separately. A value of P<0.05 was considered statistically significant.
Nine patients were recruited. The mean age was 49.6 (range 2572) and the mean weight was 73.2 (13.8) kg. The effects of diclofenac on physiological variables are shown in Table 1. There was no statistical difference between measurements of CBFV at 15 and 40 min compared with baseline. No statistical differences were found between the physiological variables of mean arterial pressure, heart rate, temperature, and arterial oxygen and carbon dioxide pressures. Results of the tissue analysis in the nine volunteers revealed five gliomas, two astrocytomas, one lymphoma and one inflammatory tissue.
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Comments |
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Indomethacin, another NSAID, is a potent cerebral vasoconstrictor. It decreases CBF by up to 40% without a change in cerebral metabolic rate, similar to the effects of hypocapnia. However, this effect appears to be unique among the NSAIDs. Its mechanism of cerebral vasoconstriction is still uncertain, but seems to result from mechanisms other than prostaglandin inhibition.7 The role of NSAIDs in the management of cerebral injury has also been investigated. NSAIDs may improve collateral circulation in ischaemic brain and prevent cerebral vasospasm following subarachnoid haemorrhage.8 9 Indomethacin has been used to control intracranial pressure and improve operating conditions in patients with cerebral tumours.10
We chose to study patients with intracerebral pathology as this may alter CBF and its regulation, and for the practical reason that this reflects our clinical patient population likely to receive diclofenac. As our numbers are small, we may have overlooked a significant response to diclofenac with a given tumour type, although no trend was seen.
Absolute CBF cannot be inferred from measurements of CBFV because the diameter of the insonated vessel segment is unknown. Despite this, the use of the TCD to measure CBFV has been shown to provide a good correlation between changes in flow velocity and cerebral blood flow as long as measurement conditions such as insonation angle and depth remain constant.11
In conclusion, we have shown that there is no significant change in CBFV after the administration of diclofenac in a small group of patients with supratentorial tumours.
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References |
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