Post Your Cases > Torsades after only 6 cc of .25% bupiv
vivek, many thanks for posting this case. it is another important case. first, let me point out that there are reports of bupivacaine toxicity occuring at extremely low doses. for instance: 1. Weinberg GL, Laurito CE, Geldner P, Pygon BH, Burton BK: Malignant ventricular dysrhythmias in a patient with isovaleric acidemia receiving general and local anesthesia for suction lipectomy. J Clin Anesth 1997; 9: 668-70
2. Mather LE, Copeland SE, Ladd LA: Acute toxicity of local anesthetics: underlying pharmacokinetic and pharmacodynamic concepts. Reg Anesth Pain Med 2005; 30: 553-66
i take this as an indication that there is a subgroup of patients who are very sensitive to bupivacaine-induced cardiac toxicity. it could be on the basis of a metabolic abnormality (as in the case i reported) or something we don't know about. for instance, there are patients with subclinical mutations in a particular sodium channel, or the inward potassium rectifier channel who are asymptomatic and may have normal QT but are more prone to drug-induced QT prolongation and sudden death. as you point out, it's possible that bupivacaine, which typically prolongs QRS duration, might also lower the threshold for QT effects. we'll have to hear from an electrophysiologist. putting that aside for a minute. i want you to read the case from aggie involving a patient with haldol toxicity. as in your experience, this patient developed toursades and had rapid reversal of the multiform VT shortly after the lipid infusion. in that case, the haldol was the offending agent. in yours we can only speculate on teh role of an underlying K or Na channel issue, the effect of bupivacaine, or both. or as you put it, the possiblity that lipid has a beneficial effect on Torsades.
Now....some questions for you:
do you have ecg strips?
code sheet? (i would love to seem them).
how rapidly after the lipid did the ecg convert?
how long to normal VS?
how is the patient doing now?
was the QT post-event normal?
finally:
1. i hope that you will write this case up. the questions you raise are important to address. the case itself is very interesting and important.
2. if you can contact the patient we should get some blood for DNA to screen for the common sodium or potassium channel mutations.
thanks again,
great case,
great save!!!!
congrats,
guy
2. Mather LE, Copeland SE, Ladd LA: Acute toxicity of local anesthetics: underlying pharmacokinetic and pharmacodynamic concepts. Reg Anesth Pain Med 2005; 30: 553-66
i take this as an indication that there is a subgroup of patients who are very sensitive to bupivacaine-induced cardiac toxicity. it could be on the basis of a metabolic abnormality (as in the case i reported) or something we don't know about. for instance, there are patients with subclinical mutations in a particular sodium channel, or the inward potassium rectifier channel who are asymptomatic and may have normal QT but are more prone to drug-induced QT prolongation and sudden death. as you point out, it's possible that bupivacaine, which typically prolongs QRS duration, might also lower the threshold for QT effects. we'll have to hear from an electrophysiologist. putting that aside for a minute. i want you to read the case from aggie involving a patient with haldol toxicity. as in your experience, this patient developed toursades and had rapid reversal of the multiform VT shortly after the lipid infusion. in that case, the haldol was the offending agent. in yours we can only speculate on teh role of an underlying K or Na channel issue, the effect of bupivacaine, or both. or as you put it, the possiblity that lipid has a beneficial effect on Torsades.
Now....some questions for you:
do you have ecg strips?
code sheet? (i would love to seem them).
how rapidly after the lipid did the ecg convert?
how long to normal VS?
how is the patient doing now?
was the QT post-event normal?
finally:
1. i hope that you will write this case up. the questions you raise are important to address. the case itself is very interesting and important.
2. if you can contact the patient we should get some blood for DNA to screen for the common sodium or potassium channel mutations.
thanks again,
great case,
great save!!!!
congrats,
guy
November 12, 2007 |
[Guy Weinberg]
[Guy Weinberg]
Interesting case. Sounds like your patient had LQTS type 1. Was the QTc of 479 that you mentioned pre-op? We have been looking at the effect of anaesthetic drugs on myocardial repolarisation dynamics &, in particular, at the time interval between the peak & the end of the T wave, which appears to be a better predictor of torsadogenicity than the QT interval. I'd be really interested to know what your patient's pre-op & post-event Tp-e intervals were. I have no idea why Intralipid helped, but am very pleased that it did! Maybe we should look at the effect of Intralipid on Tp-e...
Simon
Simon
April 3, 2008 |
Simon Whyte
Simon Whyte
Simon,
thanks for the input. i was also interested in your refinement of the QT metric and would love to learn more. please note the haldol case posted herein by agnes hewitt. this patient's QT was prolonged baseline, made worse by a haldol injection, then devolved to torsades. all documented on ECG. she converted spontaneously to sinus tachy with lipid infusion. just awesome. guido plotted out the QT vs time and the effect of lipid is very pronounced. patient did very well and even posted a 'thank you'. please give us some citations referencing your new QT metric.
thanks
guy
thanks for the input. i was also interested in your refinement of the QT metric and would love to learn more. please note the haldol case posted herein by agnes hewitt. this patient's QT was prolonged baseline, made worse by a haldol injection, then devolved to torsades. all documented on ECG. she converted spontaneously to sinus tachy with lipid infusion. just awesome. guido plotted out the QT vs time and the effect of lipid is very pronounced. patient did very well and even posted a 'thank you'. please give us some citations referencing your new QT metric.
thanks
guy
April 7, 2008 |
[Guy Weinberg]
[Guy Weinberg]
Sorry for the long delay in replying.
Vivek, have you seen this article?
Long QT 1 mutation KCNQ1 A344V increases local anesthetic sensitivity of the slowly activating delayed rectifier potassium current. Siebrands CC, Binder S, Eckhoff U, Schmitt N, Friederich P. Anesthesiology. 2006 Sep;105(3):511-20.
I wonder if this is the LQT! genotype of your patient?
Re 'my' QT metric - the concept of Tp-e being a better predictor of torsadogenicity than QTc is based on electrophysiological work from the labs of Charles Antzelevitch & Walter Shimizu labs. To try to summarise a complicated idea, they have shown that different parts of the myocardial wall repolarise at different rates; this phenomenon is responsible for the shape of the T wave & produces physiological transmural dispersion of repolarisation across the myocardial wall. Exaggeration of this phenomenon increases differential refractoriness within the myocardial wall, which creates a milieu in which early after-depolarisations can set up intramyocardial re-entrant circuits. This is believed to be the final common electrophysiological pathway for the initiation & propagation of torsades in LQTS (& also in short QT, Brugada & arrhythmogenic right ventricular dysplasia syndromes).
Some bedtime reading for insomniacs:
Yan GX, Antzelevitch C. Cellular basis for the normal T wave and the electrocardiographic manifestations of the long-QT syndrome. Circulation 1998;98:1928 –36.
Shimizu W, Antzelevitch C. Sodium channel block with mexiletine is effective in reducing dispersion of repolarization and preventing torsade des pointes in LQT2 and LQT3 models of the long-QT syndrome. Circulation 1997;96:2038 – 47.
Shimizu W, Antzelevitch C. Differential effects of B-adrenergic agonists and antagonists in LQT1, LQT2 and LQT3 models of the long QT syndrome. J Am Coll Cardiol 2000;35:778 – 86.
Shimizu W, Antzelevitch C. Cellular basis for the ECG features of the LQT1 form of the long-QT syndrome: effects of B-adrenergic agonists and antagonists and sodium channel blockers on transmural dispersion of repolarization and torsade de pointes. Circulation 1998;98:2314–22.
Whyte SD, Booker PD, Buckley DG. The effects of propofol and sevoflurane on the QT interval and transmural dispersion of repolarization in children. Anesth Analg 2005;100:71–7.
Antzelevitch C, Shimizu W, Yan GX, Sicouri S. Cellular basis for QT dispersion. J Electrocardiol 1998;30(Suppl):168 –75.
Antzelevitch C, Shimizu W, Yan GX, et al. The M cell: its contribution to the ECG and to normal and abnormal electrical function of the heart. J Cardiovasc Electrophysiol 1999;10:1124 –52.
Vivek, have you seen this article?
Long QT 1 mutation KCNQ1 A344V increases local anesthetic sensitivity of the slowly activating delayed rectifier potassium current. Siebrands CC, Binder S, Eckhoff U, Schmitt N, Friederich P. Anesthesiology. 2006 Sep;105(3):511-20.
I wonder if this is the LQT! genotype of your patient?
Re 'my' QT metric - the concept of Tp-e being a better predictor of torsadogenicity than QTc is based on electrophysiological work from the labs of Charles Antzelevitch & Walter Shimizu labs. To try to summarise a complicated idea, they have shown that different parts of the myocardial wall repolarise at different rates; this phenomenon is responsible for the shape of the T wave & produces physiological transmural dispersion of repolarisation across the myocardial wall. Exaggeration of this phenomenon increases differential refractoriness within the myocardial wall, which creates a milieu in which early after-depolarisations can set up intramyocardial re-entrant circuits. This is believed to be the final common electrophysiological pathway for the initiation & propagation of torsades in LQTS (& also in short QT, Brugada & arrhythmogenic right ventricular dysplasia syndromes).
Some bedtime reading for insomniacs:
Yan GX, Antzelevitch C. Cellular basis for the normal T wave and the electrocardiographic manifestations of the long-QT syndrome. Circulation 1998;98:1928 –36.
Shimizu W, Antzelevitch C. Sodium channel block with mexiletine is effective in reducing dispersion of repolarization and preventing torsade des pointes in LQT2 and LQT3 models of the long-QT syndrome. Circulation 1997;96:2038 – 47.
Shimizu W, Antzelevitch C. Differential effects of B-adrenergic agonists and antagonists in LQT1, LQT2 and LQT3 models of the long QT syndrome. J Am Coll Cardiol 2000;35:778 – 86.
Shimizu W, Antzelevitch C. Cellular basis for the ECG features of the LQT1 form of the long-QT syndrome: effects of B-adrenergic agonists and antagonists and sodium channel blockers on transmural dispersion of repolarization and torsade de pointes. Circulation 1998;98:2314–22.
Whyte SD, Booker PD, Buckley DG. The effects of propofol and sevoflurane on the QT interval and transmural dispersion of repolarization in children. Anesth Analg 2005;100:71–7.
Antzelevitch C, Shimizu W, Yan GX, Sicouri S. Cellular basis for QT dispersion. J Electrocardiol 1998;30(Suppl):168 –75.
Antzelevitch C, Shimizu W, Yan GX, et al. The M cell: its contribution to the ECG and to normal and abnormal electrical function of the heart. J Cardiovasc Electrophysiol 1999;10:1124 –52.
June 16, 2008 |
Simon Whyte
Simon Whyte
simon,
thanks for the refs. i'm enough of a nerd that i'll read most of them. the Tp-e is a very interesting concept......
guy
thanks for the refs. i'm enough of a nerd that i'll read most of them. the Tp-e is a very interesting concept......
guy
June 17, 2008 |
[Guy Weinberg]
[Guy Weinberg]
Points to consider: bupiv changed the threshold for QT prolongation leading to torsades. Intralipid may have a role in this arrhytmia??
Please contact me with any suggestions or thoughts,
Vivek Moitra, MD