Neurnradiolngg
Neuroradiology 13, 195-199 (1977)
© by Springer-Verlag 1977
Cardiovascular Reactions to Myelography with Watersoluble Contrast Media J. Pra~stholm and S. Moiler Department of Neuroradiology, Rigshospitalet, and Institutes of Experimental Research in Surgery and of Neuropathology, University of Copenhagen, Copenhagen, Denmark
Summary. Arterial blood pressure and heart rate were recorded for 5 to 7 h during myelography with iothalamate meglumine and metrizamide in 23 rabbits. After 0.6 ml iothalamate meglumine containing 280 mg I/ml a significant decrease in blood pressure and signs of circulatory failure were found. After identical doses of metrizamide and after reduction of the dose of iothalamate meglumine to 0.4 ml containing 1 4 0 m g I / m l no significant fall in blood pressure was recorded. A decrease of blood pressure was always accompanied by a decrease of heart rate. Arterial blood pressure and heart rate during experimental myelography are suggested as useful variables in the evaluation and comparison of new contrast media for myelography.
Key words: Myelography - Watersoluble contrast media - Cardiovascular reactions.
A fall of arterial blood pressure, with the risk of development of shock, was one of the hazards of myelography with sodium methiodal (Abrodil, Conturex, Kontrast-U) [1, 5]. As sodium methiodal was a strong irritant, a spinal anesthetic was required, and the fall in blood pressure was explained by peripheral vasodilatation due to paralysis of the vasoconstrictive axons in the anterior nerve roots. The great advantage of iothalamate meglumine (Conray Meglumin 282, Conray 60%, Contrix 28) for lumbar myelography is that spinal anesthesia is unnecessary. Muscular spasms showed, however, that iothalamate meglumine had some effect on the nervous system. It was therefore decided to study its influence on such autonomic functions as regulation of blood pressure and heart rate during experimental myelography.
Material and Method Adult rabbits with an average weight of 3.8 kg (range 2.9-5.5 kg) were employed. Under intravenous sodium pentobarbital (Nembutal) anesthesia, with an initial dose of 36 mg/kg body weight, the right femoral artery was exposed and a polyethylene catheter introduced into the aorta. With the rabbit lying in the right lateral position the arterial blood pressure was measured through the catheter using a statham pressure transducer (0-300 mm Hg). The mean arterial pressure was calculated as the mean value of the systolic and diastolic pressures measured. The heart rate was recorded with ECG needle electrodes in the forelimbs. The variables were monitored continuously and recorded with an ElemaSch6nander Mingograf. With the rostral end of the rabbit elevated, the subarachnoid space was punctured in the suboccipital region with a stenstr6m cannula, pointing caudad. About 0.5 ml of CSF was aspirated and the contrast medium injected. The rostral end was kept elevated for another 10 rain to facilitate distribution in the spinal canal. Radiographs of the skull and entire spine were taken to check on the correct distribution of the contrast medium. The contrast media employed were iothalamate meglumine in a dose of either 0.6 ml containing 280 mg iodine/ml in 10 rabbits, or 0.4 ml containing 140 mg iodine/ml in 7 rabbits, or metrizamide (Amipaque) in a dose of 0.6 ml containing 280 mg iodine/ml in 6 rabbits. It was necessary to maintain the anesthesia during the entire observation period to avoid convulsions after iothalamate meglumine. The additional dose of pentobarbital for all myelographies ranged from 5.5 to 17 mg/kg body weight/h with an average of 10 mg/kg/h. A control group of 4 rabbits underwent prolonged pentobarbital anesthesia alone in
196
J. Pra~stholm and S. Moller: Cardiovascular Reactions to Myelography
Fig. 1. Myelogram of a rabbit after suboccipital injection of 0.6 ml metrizamide 280 mg I/ml
BP
EP mm ~9
mmHg I
150
1 O0
0C--
50
5(
2
3
4
5
6
? time
0
-2
1
2
3
t,
5 time
in h o u r s
in h o u r s
Fig. 4
Fig. 2
BP
BP mmHg
mr Hg'
150
50
i
0C
5O
50
-1
0
I
2
3
4
5 t i m e in hours
Fig. 3
-I
0
1
3 t i m e in
5 hours
Fig. 5
Fig. 2. Mean arterial blood pressure in 4 rabbits during i.v. pentobarbital anesthesia with an initial dose of 32 mg/kg and a maintenance dose of 16 mg/kg/h
Figs. 3-5. Mean arterial blood pressure in rabbits during myelography. Time from - 2 h to - 1 5 rain was called the premyelographic period, and from + 1 h and thereafter the postmyelographic period. Arrow indicates time of contrast medium injection
Fig. 3. 10 rabbits with 0.6 ml iothalamate meglumine 280 mg I/ml Fig. 4. 7 rabbits with 0.4 ml iothalamate meglumine 140 mg I/ml Fig. 5. 6 rabbits with 0.6 ml metrizamide 280 mg I/ml
197
J. Pr~estholm and S. Moiler: Cardiovascular Reactions to Myelography
order to evaluate the possible influence of the anesthesia on the blood pressure and heart rate. The initial dose was 32 mg/kg and the additional doses 16 mg/kg/h in this series. The rabbits were killed under the same anesthesia after a recording period of about 7 h, either by bleeding or cardiac perfusion with formalin. Histological examinations were made on slides from 12 segments of the spinal cord evenly distributed from C 1 to $3 using the following staining methods: hematoxylin-eosin, van Gieson, Kliiver-Barrera and Einarson (gallocyanine chromalum).
Statistical Method Statistical analysis was carried out on measurements of blood pressure and heart rate obtained during a premyelographic period of about 2 h ending 15 min before the injection of contrast medium, and from a postmyelographic period of about 5 h beginning 1 h after the injection (Figs. 3-5). No statistical calculations were made on the variations of blood pressure and heart rate during the puncture and the initial postpuncture phase from - 1 5 min to + 1 h. Measurements every 15 min were used in the calculations. First the two variables and the two periods were analyzed independently four times using the same statistical tests. Then the two periods were compared within each rabbit. As the observation periods were unequal, it was first determined for each rabbit whether the observations were time-dependent, using a linear regression analysis. Only the blood pressure during the postmyelographic period, for all rabbits independent of treatment, showed a systematic time trend different from zero, with mean - 1 . 4 mm Hg. A similar time trend was seen in 4 rabbits during prolonged anesthesia alone. As the postmyelographic period investigated was from 2 to 4 h, this decrease in blood pressure was insignificant, and we continued the analysis on the assumption that there was no time effect in any of the two periods. The variations within a rabbit, between rabbits with the same experimental procedure, and between groups of rabbits with different experimental procedures, were compared by a hierarchic analysis of variances using one way classifications. As the rabbits had different levels of blood pressure and heart rate in the premyelographic period, the mean values of observations during the pre- and postmyelographic periods were compared in each rabbit using Student's t test on the difference of the means. The effects of the treatments were compared in groups of rabbits using Wilcoxon's rank sum test on the difference of the means in each rabbit.
Results A contrast medium dose of 0.6ml containing 280 mg iodine/ml gave excellent outlining of the total spinal subarachnoid space (Fig. 1), while a dose of 0.4 ml containing 140 mg iodine/ml gave a less complete myelogram. Intracranial distribution of the contrast medium was not seen. A steep rise of blood pressure was noted in connection with the suboccipital puncture and the injection of the contrast medium. This rise started when the rabbit's head was bent forward and immobilized for the suboccipital puncture and was also seen when there was a simple puncture without any injection. The mean rise of blood pressure in two cases of a simple puncture with aspiration of CSF was 35 mm Hg. A similar initial rise was recorded during the suboccipital puncture just before the injection of contrast medium. There was a further rise in all rabbits during this injection, to an average level of 42 mm Hg above the prepuncture pressure. After injection of the contrast medium there was a gradual fall in blood pressure during the first hour (Figs. 3-5). The results of the analysis of variances are given in Table 1. There was a significant difference between the individual rabbits and this difference increased after myelography. But even with this greater variance there was a significant difference between groups receiving different kinds and doses of contrast medium. The mean arterial blood pressure in the individual rabbits in the pre- and postmyelographic period is shown in Figure 6. There was a fall in the blood pressure of almost all rabbits in all myelography groups, viz.nearly all symbols in Figure 6 are below the line of identity showed. This fall was shown to be significant by t tests in 9 of 10 rabbits after 0.6ml iothalamate meglumine 2 8 0 m g I / m l (average - 2 8 m m H g ) , in 4 of 7 rabbits after 0.4 ml iothalamate meglumine 140 mg I/ml (average - 1 0 mm Hg), and in 4 of 6 rabbits after 0.6 ml metrizamide 280 mg I/ml (average - 4 mm Hg). The wilcoxon rank sum test did not show any significant difference between rabbits receiving 0.6 ml metrizamide 280 mg I/ml and rabbits receiving 0.4 ml iothalamate meglumine 140 mg I/ml (p > 0.10), while there was a significant difference between these two groups and the group of rabbits receiving 0.6 ml iothalamate meglumine 280 mg I/ml (p < 0.01). In accepting a systematic time trend of - 1.4 mm Hg/h, which was also found to be present in the group of 4 rabbits with prolonged anesthesia alone (Fig. 2), we would expect a difference between the premyelographic and postmyelographic period of - 5 . 6 mm Hg, as the time difference between the midpoints of the two observation periods
198
J. Prmstholm and S. Moller: Cardiovascular Reactions to Myelography
Table 1. The analysis of variances of blood pressure and heart rate in rabbits in a premyelographic and a postmyelographic period (Figs. 3-5). All data from rabbits with prolonged anesthesia only (Fig. 2) were included in the "postmyelographic" period Blood pressure in
Heart rate in
premyelographic period
postmyelographic period
premyelographic period
s2
f
s2
f
S2
f
44
92
50
447
112
68
Variation between individuals with same treatment
267
20
Neuroradiology 13, 195-199 (1977)
© by Springer-Verlag 1977
Cardiovascular Reactions to Myelography with Watersoluble Contrast Media J. Pra~stholm and S. Moiler Department of Neuroradiology, Rigshospitalet, and Institutes of Experimental Research in Surgery and of Neuropathology, University of Copenhagen, Copenhagen, Denmark
Summary. Arterial blood pressure and heart rate were recorded for 5 to 7 h during myelography with iothalamate meglumine and metrizamide in 23 rabbits. After 0.6 ml iothalamate meglumine containing 280 mg I/ml a significant decrease in blood pressure and signs of circulatory failure were found. After identical doses of metrizamide and after reduction of the dose of iothalamate meglumine to 0.4 ml containing 1 4 0 m g I / m l no significant fall in blood pressure was recorded. A decrease of blood pressure was always accompanied by a decrease of heart rate. Arterial blood pressure and heart rate during experimental myelography are suggested as useful variables in the evaluation and comparison of new contrast media for myelography.
Key words: Myelography - Watersoluble contrast media - Cardiovascular reactions.
A fall of arterial blood pressure, with the risk of development of shock, was one of the hazards of myelography with sodium methiodal (Abrodil, Conturex, Kontrast-U) [1, 5]. As sodium methiodal was a strong irritant, a spinal anesthetic was required, and the fall in blood pressure was explained by peripheral vasodilatation due to paralysis of the vasoconstrictive axons in the anterior nerve roots. The great advantage of iothalamate meglumine (Conray Meglumin 282, Conray 60%, Contrix 28) for lumbar myelography is that spinal anesthesia is unnecessary. Muscular spasms showed, however, that iothalamate meglumine had some effect on the nervous system. It was therefore decided to study its influence on such autonomic functions as regulation of blood pressure and heart rate during experimental myelography.
Material and Method Adult rabbits with an average weight of 3.8 kg (range 2.9-5.5 kg) were employed. Under intravenous sodium pentobarbital (Nembutal) anesthesia, with an initial dose of 36 mg/kg body weight, the right femoral artery was exposed and a polyethylene catheter introduced into the aorta. With the rabbit lying in the right lateral position the arterial blood pressure was measured through the catheter using a statham pressure transducer (0-300 mm Hg). The mean arterial pressure was calculated as the mean value of the systolic and diastolic pressures measured. The heart rate was recorded with ECG needle electrodes in the forelimbs. The variables were monitored continuously and recorded with an ElemaSch6nander Mingograf. With the rostral end of the rabbit elevated, the subarachnoid space was punctured in the suboccipital region with a stenstr6m cannula, pointing caudad. About 0.5 ml of CSF was aspirated and the contrast medium injected. The rostral end was kept elevated for another 10 rain to facilitate distribution in the spinal canal. Radiographs of the skull and entire spine were taken to check on the correct distribution of the contrast medium. The contrast media employed were iothalamate meglumine in a dose of either 0.6 ml containing 280 mg iodine/ml in 10 rabbits, or 0.4 ml containing 140 mg iodine/ml in 7 rabbits, or metrizamide (Amipaque) in a dose of 0.6 ml containing 280 mg iodine/ml in 6 rabbits. It was necessary to maintain the anesthesia during the entire observation period to avoid convulsions after iothalamate meglumine. The additional dose of pentobarbital for all myelographies ranged from 5.5 to 17 mg/kg body weight/h with an average of 10 mg/kg/h. A control group of 4 rabbits underwent prolonged pentobarbital anesthesia alone in
196
J. Pra~stholm and S. Moller: Cardiovascular Reactions to Myelography
Fig. 1. Myelogram of a rabbit after suboccipital injection of 0.6 ml metrizamide 280 mg I/ml
BP
EP mm ~9
mmHg I
150
1 O0
0C--
50
5(
2
3
4
5
6
? time
0
-2
1
2
3
t,
5 time
in h o u r s
in h o u r s
Fig. 4
Fig. 2
BP
BP mmHg
mr Hg'
150
50
i
0C
5O
50
-1
0
I
2
3
4
5 t i m e in hours
Fig. 3
-I
0
1
3 t i m e in
5 hours
Fig. 5
Fig. 2. Mean arterial blood pressure in 4 rabbits during i.v. pentobarbital anesthesia with an initial dose of 32 mg/kg and a maintenance dose of 16 mg/kg/h
Figs. 3-5. Mean arterial blood pressure in rabbits during myelography. Time from - 2 h to - 1 5 rain was called the premyelographic period, and from + 1 h and thereafter the postmyelographic period. Arrow indicates time of contrast medium injection
Fig. 3. 10 rabbits with 0.6 ml iothalamate meglumine 280 mg I/ml Fig. 4. 7 rabbits with 0.4 ml iothalamate meglumine 140 mg I/ml Fig. 5. 6 rabbits with 0.6 ml metrizamide 280 mg I/ml
197
J. Pr~estholm and S. Moiler: Cardiovascular Reactions to Myelography
order to evaluate the possible influence of the anesthesia on the blood pressure and heart rate. The initial dose was 32 mg/kg and the additional doses 16 mg/kg/h in this series. The rabbits were killed under the same anesthesia after a recording period of about 7 h, either by bleeding or cardiac perfusion with formalin. Histological examinations were made on slides from 12 segments of the spinal cord evenly distributed from C 1 to $3 using the following staining methods: hematoxylin-eosin, van Gieson, Kliiver-Barrera and Einarson (gallocyanine chromalum).
Statistical Method Statistical analysis was carried out on measurements of blood pressure and heart rate obtained during a premyelographic period of about 2 h ending 15 min before the injection of contrast medium, and from a postmyelographic period of about 5 h beginning 1 h after the injection (Figs. 3-5). No statistical calculations were made on the variations of blood pressure and heart rate during the puncture and the initial postpuncture phase from - 1 5 min to + 1 h. Measurements every 15 min were used in the calculations. First the two variables and the two periods were analyzed independently four times using the same statistical tests. Then the two periods were compared within each rabbit. As the observation periods were unequal, it was first determined for each rabbit whether the observations were time-dependent, using a linear regression analysis. Only the blood pressure during the postmyelographic period, for all rabbits independent of treatment, showed a systematic time trend different from zero, with mean - 1 . 4 mm Hg. A similar time trend was seen in 4 rabbits during prolonged anesthesia alone. As the postmyelographic period investigated was from 2 to 4 h, this decrease in blood pressure was insignificant, and we continued the analysis on the assumption that there was no time effect in any of the two periods. The variations within a rabbit, between rabbits with the same experimental procedure, and between groups of rabbits with different experimental procedures, were compared by a hierarchic analysis of variances using one way classifications. As the rabbits had different levels of blood pressure and heart rate in the premyelographic period, the mean values of observations during the pre- and postmyelographic periods were compared in each rabbit using Student's t test on the difference of the means. The effects of the treatments were compared in groups of rabbits using Wilcoxon's rank sum test on the difference of the means in each rabbit.
Results A contrast medium dose of 0.6ml containing 280 mg iodine/ml gave excellent outlining of the total spinal subarachnoid space (Fig. 1), while a dose of 0.4 ml containing 140 mg iodine/ml gave a less complete myelogram. Intracranial distribution of the contrast medium was not seen. A steep rise of blood pressure was noted in connection with the suboccipital puncture and the injection of the contrast medium. This rise started when the rabbit's head was bent forward and immobilized for the suboccipital puncture and was also seen when there was a simple puncture without any injection. The mean rise of blood pressure in two cases of a simple puncture with aspiration of CSF was 35 mm Hg. A similar initial rise was recorded during the suboccipital puncture just before the injection of contrast medium. There was a further rise in all rabbits during this injection, to an average level of 42 mm Hg above the prepuncture pressure. After injection of the contrast medium there was a gradual fall in blood pressure during the first hour (Figs. 3-5). The results of the analysis of variances are given in Table 1. There was a significant difference between the individual rabbits and this difference increased after myelography. But even with this greater variance there was a significant difference between groups receiving different kinds and doses of contrast medium. The mean arterial blood pressure in the individual rabbits in the pre- and postmyelographic period is shown in Figure 6. There was a fall in the blood pressure of almost all rabbits in all myelography groups, viz.nearly all symbols in Figure 6 are below the line of identity showed. This fall was shown to be significant by t tests in 9 of 10 rabbits after 0.6ml iothalamate meglumine 2 8 0 m g I / m l (average - 2 8 m m H g ) , in 4 of 7 rabbits after 0.4 ml iothalamate meglumine 140 mg I/ml (average - 1 0 mm Hg), and in 4 of 6 rabbits after 0.6 ml metrizamide 280 mg I/ml (average - 4 mm Hg). The wilcoxon rank sum test did not show any significant difference between rabbits receiving 0.6 ml metrizamide 280 mg I/ml and rabbits receiving 0.4 ml iothalamate meglumine 140 mg I/ml (p > 0.10), while there was a significant difference between these two groups and the group of rabbits receiving 0.6 ml iothalamate meglumine 280 mg I/ml (p < 0.01). In accepting a systematic time trend of - 1.4 mm Hg/h, which was also found to be present in the group of 4 rabbits with prolonged anesthesia alone (Fig. 2), we would expect a difference between the premyelographic and postmyelographic period of - 5 . 6 mm Hg, as the time difference between the midpoints of the two observation periods
198
J. Prmstholm and S. Moller: Cardiovascular Reactions to Myelography
Table 1. The analysis of variances of blood pressure and heart rate in rabbits in a premyelographic and a postmyelographic period (Figs. 3-5). All data from rabbits with prolonged anesthesia only (Fig. 2) were included in the "postmyelographic" period Blood pressure in
Heart rate in
premyelographic period
postmyelographic period
premyelographic period
s2
f
s2
f
S2
f
44
92
50
447
112
68
Variation between individuals with same treatment
267
20
