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*Department of Anesthesiology and
Cardiology Unit, Centro Traumatologico Ortopedico, Azienda Ospedaliera Careggi, Firenze, Italia
Address correspondence and reprint requests to Salvatore Sia, MD, Via Santelli, 41, 50134, Firenze, Italy. Address e-mail to sia3{at}interfree.it
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Abstract |
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IMPLICATIONS: Sudden hypotensive and/or bradycardic events occur during shoulder surgery in the sitting position during interscalene block. In this study, we demonstrated that the presence of epinephrine in the local anesthetic mixture significantly increases the incidence of these events.
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Introduction |
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Methods |
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7 and 
12 h in all patients. After a peripheral IV infusion was begun and baseline HR and systolic BP had been recorded, the patients received an interscalene brachial plexus block using a peripheral nerve stimulator (Stimuplex; Braun, Melsugen, Germany). All patients received fentanyl 1 µg/kg and midazolam 20 µg/kg IV 5 min before the block. A mixture of equal parts of 0.5% bupivacaine and 2% lidocaine was used in Group P. The same mixture with 1:200,000 epinephrine was used in Group E. The block was performed with 35 mL of solution for patients weighing <60 kg, with 40 mL for those weighing 60–80 kg, and with 45 mL for those weighing >80 kg. Patients received oxygen via nasal cannulae at the rate of 4 L/min and were monitored with continuous pulse oximetry, a noninvasive automatic BP device that was cycled every 5 min, with more frequent measurements as indicated, and continuous electrocardiography. They were then placed in the sitting position, which was achieved by elevating the back of the operating room table to 60°–80° and flexing the knees and hips to 90°. Total IV fluids were limited to 10–12 mL/kg. Midazolam was given intraoperatively at the discretion of the anesthesiologist; fentanyl was given in case of pain. The amount of each drug and a sedation score (1 = awake, 2 = awake but sedated, 3 = asleep but responsive to verbal stimuli, 4 = asleep but responsive to tactile stimuli) were recorded every 10 min. Metoprolol was given if HR >110 bpm, with or without a concomitant increase in BP. If the patient’s BP increased to levels at which visualization of the surgical field was impaired (according to the surgical perception) or to a level of systolic BP >170 mm Hg, urapidil was administered IV in 12.5-mg increments. In case of BP <110 mm Hg, no treatment was given, even if the surgeon, who was unaware of patient’s group, complained of poor visualization of the surgical field. Cardiovascular variables recorded for all patients included preanesthetic baseline, first intraoperative, and highest and lowest HR and BP. The intraoperative management was left to the discretion of the anesthesiologist who performed the ISB, and who was unaware of the patient group. A HBE was defined, according to Liguori et al. (3), as a decrease in HR of >30 bpm in <5 min or any decrease <50 bpm, and/or a systolic BP decrease of >30 mm Hg in <5 min or any decrease <90 mm Hg. This event must have been accompanied by intraoperative treatment by the attending anesthesiologist. Signs or symptoms such as lightheadedness, nausea, and sweating were recorded but were not necessary in defining a HBE. If the event was solely a decrease in systolic BP without any other hemodynamic alteration, and occurred within 15 min after urapidil therapy, the event was discounted. Similarly, if the event was solely a decrease in HR, and occurred within 15 min after metoprolol therapy, it was also discounted. If the interval between the ISB and the end of surgery was <70 min, the patient was excluded from the study.
Data were analyzed using SPSS 8.0 for Windows (SPSS Inc., Chicago, IL) and Power and PrecisionTM (Biostat Inc., Englewood, NJ) software packages. Parametric variables were described as mean ± SD; qualitative variables as number (percentage) and as median and ranges. Student’s t-test, Fisher’s exact test, or Mann-Whitney U-test was used as appropriate to compare the two groups. P < 0.05 was considered significant.
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Results |
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There were no differences between groups with regard to age, sex, weight, ASA physical status, side of surgery, and baseline HR and BP (Table 1). No patients experienced any symptoms suggestive of spinal or epidural blockade or intravascular injection. The incidence of HBE was 11% and 29% in Group P and Group E, respectively (P = 0.015) (Table 2). Of the 22 patients who had a HBE, 7 had bradycardia, 1 had hypotension, and 14 had both bradycardia and hypotension. First intraoperative and highest BP and HR were significantly higher in Group E (P = 0.000) (Table 2). The value of BP recorded when the surgeon complained of impaired visualization of the field was 165 ± 13 mm Hg. The incidence of urapidil use was significantly more in Group E (31% versus 13%; P = 0.018). Four patients in Group E and 2 in Group P developed a decrease in systolic BP of >30 or to <90 mm Hg within 15 min of receiving urapidil and were not included as HBE. Five HBEs in Group E and four in Group P were induced by urapidil administration. All the "urapidil-induced" HBE occurred within 15 min of administration of the drug. The incidence of HBE was more frequent in the 24 patients who received urapidil than in the 86 who did not (37% versus 15%; P = 0.01). The 17 patients in Group E treated for hypertension received 29 ± 11 mg of urapidil and the 7 in Group P 30 ± 12 mg. When considering for the statistical analysis only those patients who did not receive urapidil or metoprolol, the incidence of HBE was more frequent in Group E (37 patients) than in Group P (48 patients) (29% versus 4%; P = 0.001). The dose of epinephrine administered to Group E patients was 200 ± 13 µg. Metoprolol was given to three patients in Group E and one in Group P; none of these experienced an HBE. Prodromal symptoms (nausea, sweating, light-headedness) were recorded in 12 patients in Group E and in 4 in Group P. Therapy of HBEs consisted of atropine (n = 13) and/or ephedrine (n = 15). In comparing the 22 patients in the 2 groups who did experience a HBE with the 98 patients who did not, highest and lowest HR and BP were significantly different, as shown in Table 3. The incidence of urapidil use was significantly more frequent in HBE patients (P = 0.01). Fentanyl was administered to three patients in Group E and two in Group P. The amount of fentanyl administered to these patients did not differ between the groups (83 ± 28 versus 75 ± 35 µg). Three patients in Group E and four in Group P received midazolam. The amount of midazolam administered to these patients did not differ between the groups (2.6 ± 1.1 versus 2.5 ± 1 mg).
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Discussion |
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One proposed mechanism for the occurrence of HBE (2) is based on activation of the BJR. This reaction may be related to venous pooling (caused by the sitting position and epinephrine-induced ß2-adrenergic effect) and increased inotropy (ß-adrenergic effect of epinephrine). Increased epinephrine levels may occur endogenously from decreased venous return and carotid baroreceptor stimulation, as well as exogenously from epinephrine administered with the local anesthetic or in the irrigating solution. In this setting, a low-volume hypercontractile ventricle causes stimulation of intramyocardial mechanoreceptors (C fibers), which is followed, in susceptible patients, by an abrupt withdrawal of sympathetic outflow and an increase in vagal tone with resultant bradycardia and hypotension. This scenario is similar to that incurring during tilt-table testing in patients with unexplained syncope: when the patients do not respond to a decrease in ventricular volume (caused by the tilt), the procedure is repeated adding a continuous infusion of isoproterenol which causes a hypercontractile cardiac state (5,6). This procedure increases the frequency with which vasovagal reactions are induced (5). Epinephrine at small dose has primarily ß-adrenergic agonist activity, similar to isoproterenol. Therefore, it might be hypothesized that even a small epinephrine dose, such as that administered with the local anesthetic mixture for the ISB, can result in a blood level sufficient, in some patients, to incite the BJR when associated with the placement of the patient in the sitting position.
This is the first prospective and randomized study testing this hypothesis. In Group P patients, who did not receive exogenous epinephrine, the incidence of HBE was significantly less than in Group E patients (11% versus 29%; P = 0.018). These results may indicate that exogenous epinephrine may be a contributor to the occurrence of HBE. Endogenous catecholamines may also have had a role in our awake patient population. A less-sedated patient may have more endogenous catecholamines, so one might predict that sedation may be beneficial in preventing HBEs. However, we found no difference in mean sedation score for patients who did develop HBE compared with those who did not.
There are few previous reports on these events. Roch and Sharrock1 reported a 24% incidence of sudden hypotension and bradycardia in shoulder arthroscopy patients in the sitting position using ISB. The administration of ß-adrenergic blockers was not addressed.
D’Alessio et al. (2), in a retrospective study including 116 patients, reported a 17% incidence of HBE. ß-Blocker drugs were administered in 15% of patients to treat tachycardia and/or hypertension; none of these patients experienced a HBE. The authors hypothesized that the administration of ß-adrenergic blockers during the early phases of tachycardia and increasing BP, may have interrupted the early stages of the BJR (2). Analogous with this hypothesis, the administration of ß-adrenergic blockers was effective in preventing the vasovagal reactions during tilt testing (7), particularly when an isoproterenol infusion was required to induce the vasovagal reaction.
The beneficial effect of ß-adrenergic blockers in preventing HBEs was not found in a second retrospective study by Kahn and Hargett (4), who reported a 13% incidence of HBE; a similar proportion of patients had received a ß-adrenergic blocker in the group who had a HBE compared with those who did not (20% versus 18%). However ß-blockers were presumably given to treat tachycardia with or without hypertension. This suggests a state of higher sympathetic tone that could predispose patients to subsequent HBEs. The authors hypothesized that the incidence of HBEs in those patients might have been more frequent had it not been for the effect of the ß-blocker, which decreased the incidence to that seen in patients not given ß-blockers.
A protective role of ß-adrenergic blocker administration was confirmed by a prospective study by Liguori et al. (3), who demonstrated that metoprolol, but not glycopyrrolate, decreases the incidence of HBEs when given prophylactically immediately after the administration of the block. The incidence of HBE was 28% in the placebo group and 22% in the glycopyrrolate group; no metoprolol was given to these patients. The incidence of HBE in the metoprolol group was 5%.
Significantly larger intraoperative values of BP and HR were recorded in the present study during the procedure in Group E. These larger levels could be related to a hyperadrenergic tone induced by exogenous epinephrine. Significantly larger intraoperative levels of HR and BP were recorded in patients who had a HBE when compared with those who did not. This may confirm that a state of higher sympathetic tone could predispose susceptible patients to subsequent vasovagal episodes.
There are several limitations to this study. The long non per os interval and the limited amount of fluids given during surgery could have increased the incidence of hemodynamic instability in patients of both groups. The fluid deficit and the blood loss (usually minimal during the type of surgery included into the present study) were not assessed. Probably, perioperative administration of a large amount of IV fluids might have prevented HBE in some patients. In practice, this approach may lead to discomfort secondary to urinary bladder distention in awake patients.
The major critical aspect of the study was the need to administer an antihypertensive when the surgeon complained of impaired visualization of the surgical field. In fact, this treatment might have influenced the correct estimation of the incidence of HBE.
A significant percentage of patients in Group E (31%) required an antihypertensive. Treatment of these patients was problematic. In fact, if hypertension (with or without tachycardia) is caused by an increased sympathetic tone, the administration of a ß-adrenergic blocker should be the best therapeutical choice. However, as demonstrated by previous studies (2,3), the perioperative use of these drugs was related with a reduced incidence of HBE, especially when given during the early phases of tachycardia and increasing BP. To better evaluate the incidence of HBE in the two groups, we decided to avoid, as much as possible, the use of ß-adrenergic-blocking drugs. Therefore, we administered metoprolol only to those patients with HR >110 bpm, with or without relative hypertension. A similar problem was reported by Liguori et al. (3), who recorded a 21%–39% incidence of hypertension requiring treatment. They chose IV enalaprilat as antihypertensive because it has little effect on sympathetic tone. Intravenous enalaprilat was not available at our institution. We decided to use small boluses of urapidil to reduce BP when the surgeon complained of poor surgical visualization. Urapidil is a short-acting antihypertensive drug with an antagonist action on peripheral-acting 
1-adrenoceptor antagonist and an agonistic action on central serotonin 5-HT-1A receptors (8). It reduces BP by producing peripheral vasodilatation.
The effect of a peripheral vasodilator in patients in the sitting position under ISB, as in the present study, must be addressed. In 4 patients in Group E and in 2 in Group P, a reduction in BP >30 mm Hg after the administration of urapidil was recorded. We did not consider this hypotensive effect as HBE. A reduction in HR >30 bpm or any decrease <50 bpm, after the administration of urapidil, with or without a concomitant decrease in BP, was considered as urapidil-induced HBE. Five cases of "urapidil-induced" HBE were recorded in Group E and four in Group P. All but two of HBEs recorded in Group P were "urapidil-induced." All the "urapidil-induced" HBE occurred within 15 minutes of administration of the drug. The incidence of a bradycardic response related to the administration of small dose of a peripheral vasodilator, might be explained by the drug-induced reduction in venous return, which causes a further decrease in ventricular volume and the initiation of the BJR in the susceptible patients of both groups. Analogous with this hypothesis, two studies demonstrated the diagnostic accuracy of head-up tilt testing in patients with unexplained syncope, in which sublingual nitroglycerin was used instead of a continuous infusion of isoproterenol, in patients who do not respond to the initial tilt (9,10). Liguori and Sharrock (11) reported on seven cases of severe bradycardia and five cases of asystole that occurred during orthopedic surgery under epidural anesthesia. In five of these cases, infusions of sodium nitroprusside preceded the onset of bradycardia, and in six patients, bradycardia developed while an epinephrine infusion was administered. Four patients were concurrently receiving an infusion of both drugs. These authors hypothesized that the hyperdynamic effect of epinephrine might contribute to the reflex slowing that has been reported with the BJR, and that the sodium nitroprusside infusion caused a reduction in the central volume because of vasodilatation. These factors are probably additive when combined.
However, we think that the administration of drugs to treat hypertension and/or tachycardia in some of our patients does not invalidate the main result of the study. In fact, when considering for the statistical analysis only those patients who did not receive urapidil or metoprolol, the incidence of HBE was significantly more frequent in the 37 patients of Group E than in the 48 patients of Group P (29% versus 4%; P = 0.001), thus supporting the role of exogenous epinephrine in the genesis of HBE.
There were no differences in comparing patients who developed HBE with those who did not, with regard to baseline HR, BP, average sedation scores, or the presence of a history of syncopal episodes. There is a range of individual susceptibility to vasovagal reaction and probably different patterns of hemodynamic response (12). Vasovagal episodes are usually of minor significance, but in the extreme may lead to cardiac arrest. The inability to predict patients who are at risk of having an HBE highlights the importance of vigilance and prompt pharmacological treatment on the part of the anesthesiologist (13).
In conclusion, we have confirmed, in a prospective, randomized study, that sudden HBE may occur during shoulder surgery in the sitting position under ISB. These events are unpredictable and can be of great hemodynamic significance. The presence of epinephrine in the local anesthetic mixture for ISB significantly increases the incidence of HBE. Moreover, significantly increased BP and HR were recorded during the procedure in patients who received epine-phrine-containing solution. The use of urapidil as an antihypertensive increases the incidence of HBE. These results argue against the use of epinephrine-containing solution for ISB and for the cautious use of peripheral vasodilator drugs to decrease the BP in this setting.
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Footnotes |
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