Anesthesia Pharmacology Chapter 15: Cardiac Anesthesiology
Anesthesia Pharmacology Chapter 15: Cardiac Anesthesiology
1Kamibayashi, T, Hayashi, Y, Mammoto, T, Yamotodani, A, Taenaka, N, Yoshiya, I, Thoracic Epidural Anesthesia Attenuates Halothane-induced Myocardial Sensitization to Dysrhythmogenic Effect of Epinephrine in Dog, Anesthesiology 1995, January; 82(1): 129-134
Cardiac arrhythmias may develop in response to increase sympathetic tone.
Furthermore, interactions between epinephrine and halothane may induce arrhythmias. Thoracic epidural anesthesia induces sympathetic blockade and a question arises therefore whether or not thoracic epidural anesthesia induced sympathetic blockade might reduce the likelihood of halothane + epinephrine induce arrhythmias.
The method of assessing this question involves the use of the canine model in which dogs were anesthetized with halothane and then an epinephrine dose was administered which should induce four or more premature ventricular contractions within a 15 second period.
The question was whether the epinephrine dose required to induce this arrhythmia would be different in the presence of thoracic epidural mepivacaine or saline. Also evaluated was the effect of thoracic epidural anesthesia in bilaterally vagotomized animals.
The authors note that sympathetic nervous system activation can result in dysrhythmias particularly in the ischemic myocardium. Furthermore, the myocardium is additionally sensitized to the proarrhythmic affective epinephrine by halothane. The halothane induced myocardial sensitization epinephrine is also influenced by hemodynamic parameters and administration of intravenous drugs.
The center nervous system may also modulate the likelihood of arrhythmia development.
Clinical reports have noted that sympathetic blockade as a result of thoracic epidural anesthesia may be beneficial in management of surgical stress in heart disease patients.
44 adult dogs of either sex (8-12 kg) reused. The anesthesia was induced using halothane (1.3%) monitored using an anesthetic gas analyzer. I different dog was employed for each experiment; therefore, only one dysrhythmogenic dose (DD) was determined in any single dog. A cuffed endotracheal tube was used for incubation with subsequent mechanical ventilation. End-tidal CO2 was monitored and maintained and 35 -40 mm Hg. Esophageal temperature was maintained at 37-38.5oC. Femoral artery catheter allowed monitoring of blood pressure, blood gas & serum electrolytes. Lead II (ACG) was monitored. Femoral vein cannulation provided the route for drug administration in lactated Ringer' s solution infusion. Ringer's solution was infused at 10 ml/kg/hour. Serum potassium was maintained between 3.5 and 4.5 mEq/liter by means of potassium infusion (1-10 mEq/liter). Arterial pH, oxygen tension and serum sodium was maintained within 7.35-7.45, 85-100 mm Hg, and 135-150 mEq/l, respectively.
All under halothane anesthesia, and epidural catheter was inserted, introduced through the T 8-9 interspace into the epidural space. Following catheter advancement 5 cm cephalad, the catheter was secured to the back. Following the experiment conclusion, radiographic confirmation of catheter position was performed.
The definition of the dysrhythmias threshold was four or more premature ventricular contractions occurring within 15 seconds. The epinephrine dysrhythmia threshold dose (DD) was defined as the smallest dose required to produce the above arrhythmia sequence. This dose was determined using a protocol that specified epinephrine infusion lasting 3 minutes with a 10-30 minute recovery period between infusions. The minimum dose was 0.67 mcg/kg/minute with increasing concentration (logarithmic) increments used until the dysrhythmia threshold was determined.
Initially animals were assigned to two groups and around a manner, the epidural group and control group. The epidural group animals received epidural anesthesia with 1% mepivacaine. The initial mepivacaine dose was 0.2 ml/kg with 1/2 of the dose repeated every hour. Thirty minutes after epidural injection, epinephrine infusions were started.
Separately, in order to determine the effect of intravenous mepivacaine on halothane-epinephrine dysrhythmias, bupivacaine was administered at two doses 2 mg/kg followed by 2 mg/kg or 1 mg/kg followed by 1 mg/kg-constituting a high-dose and a low-dose sequence). For these animals, and epidural catheter was inserted and saline injected.
Epidural mepivacaine effects on halothane-epinephrine dysrhythmias in vagotomized animals was also investigated using the above procedure. Following bilateral vagotomy (C6 level sectioning), epidural catheterization was performed and epinephrine infusion initiated thirty minutes following mepivacaine administration. The dysrhythmogenic threshold was determined.
In each experiment, blood samples (5 ml) was collected, thus allowing epinephrine and mepivacaine plasma concentration determination. The analysis system had 10 pg/ml limit of sensitivity for epinephrine and norepinephrine and an inter- and intraassay variation of < 3%. For mepivacaine, sensitivity limit was 10 ng/ml with an inter- and intraassay variation of < 5%.
Data was expressed as mean +/- standard error of the mean (SEM) with results analyzed by one-way ANOVA and comparison between groups utilized Scheffe's test. Comparison of two groups utilized Student's t test with statistical significance set at 0.05.
|
The following is reference from Roger E.
Kirk's (1982) Experimental Design
(pp115-125).
|
|
. |
As shown above, although heart rate did not differ between treatment groups, systolic end-diastolic arterial pressures in the epidural mepivacaine group was lower than that observed in the control group.
Basal plasma endogenous catecholamine concentration is reported below.
Norepinephrine concentration in the epidural group was lower than that in control, although epinephrine concentration did not differ between groups. The dysrhythmia dose (DD) and epinephrine plasma concentration at dysrhythmia is noted at various mepivacaine treatment protocols.
|
. |
The dysrhythmia dose (DD) and epinephrine plasma concentration at dysrhythmia is noted at various mepivacaine treatment protocols. (see below)
|
. |
Notably, (above), Epidural mepivacaine increased the epinephrine dysrhythmic dose (DD), although mepivacaine by i.v. adminsitration had no effect
|
. |
As noted above, hemodynamic data between groups obtained at the dysrhythmia time were similar.
Plasma concentrations of mepivacaine during dysrhythmia:
mepivacaine epidural group: 1.13 +/- 0.1 ug/ml
mepivacaine i.v dose (low): 1.07 +/- 0.09 ug/ml
mepivacaine i.v. dose (high): 1.98 +/- 0.22 ug/ml
Iopamidol-based radiography confirmed average spread (C6 to T10) was similar between groups
The control, vagotomized canine group, although the epinephrine dysrhythmic dose was lower than control, the epinephrine concentration in the plasma was not changed. Antidysrhythmic characteristics of epidural mepivacaine was not seen in vagotomized animals. (see below)
|
. |
The authors point out that the principal finding in this research work was that thoracic epidural anesthesia reduced epinephrine-induced dysrhythmias occurring in the presence of halothane.
One possibility, given that mepivacaine which is a local anesthetic and accordingly possesses sodium channel blockade capabilities (class I antiarrhythmic), is that mepivacaine is acting directly on sodium channels, thus suppressing epinephrine-induced arrhythmias.
This possibility is countered by the observation that circulating mepivacaine, by contrast epidural mepivacaine, was not notably effective in changing the dysrhythmia dose for epinephrine. An additional finding arguing against a serum mepivacaine-induced effect was that the epidural mepivacaine activity itself disappeared in vagotomized animals.
Halothane-induced cardiac arrhythmias has been considered in terms of CNS involvement.
Underlying mechanisms has been unclear.
Previous work show that vagal nerve stimulation increased the dysrhythmogenic epinephrine threshold in the presence of halothane.
Additional work indicated that vagal stimulation itself could abolish dysrhythmia induced by halothane and epinephrine which occurred in the absence of vagal stimulation.
These studies all point to the importance of the parasympathetic tone in understanding these types of dysrhythmias. In the present study vagotomy reduced the dysrhythmogenic dose even though plasma concentrations were not changed. Recall that with mepivacaine epidural anesthesia, extending from C6-T10, the parasympathetic system would still be intact despite attenuation of sympathetic input to the heart (mediated by T1-T5).
Following epidural mepivacaine administration, the parasympathetic system would be relatively dominant to the sympathetic system, since the former remains intact with the latter attenuated.
This condition may be similar to vagal nerve stimulation which had been shown to prevent halothane-epinephrine induced dysrhythmias.
Consistent with this view would be the finding that epidural mepivacaine was not effective an antiarrhythmic in vagotomized animals since in the predominant vagal tone following thoracic epidural anesthesia would be lost following bilateral vagotomy.
The authors also noted the the combination of epidural anesthesia with light general anesthesia could lead to reduced postoperative complications. This consideration might apply to patients who are considered high-risk surgical candidates.
The authors current data, obtained in dogs, suggests that thoracic epidural anesthesia would reduce the likelihood of interoperative arrhythmias caused by interoperative stress + halogenated anesthetics.
Independent of this extrapolation to the human, clinical environment, the work does indicate that thoracic epidural anesthesia, at least by mepivacaine, does reduce myocardial sensitization to epinephrine by halothane -- and as a consequence reduce arrhythmias. Finally, bilateral vagotomy eliminates this effect, a finding that implicates the parasympathetic system as an influence in possible myocardial sensitization to epinephrine by halothane.
