There are few studies addressing heart rate variability in spinal anesthesia and the vast majority use linear frequency-domain methods. No study evaluating the effect of intrathecal clonidine as an adjunct to spinal anesthesia on HRV has been found. Clonidine, an α2 agonist drug acting at presynaptic receptors at the central and spinal levels, causes bradycardia and hypotension, directly interfering with heart rate variability [1,4,5].
The approximate entropy increased in T2 in group C, when compared to values in T1, but it was reduced in group B, which suggests a protective effect of clonidine. However, comparing group C at time T3 and T1, a statistically significant difference was observed, which may be suggestive of persistence of sympathetic blockade, not observed in the bupivacaine group. The entropy of the sample showed behavior similar to the approximate entropy.
The LF/HF index after spinal anesthesia in group B presented elevation from 3.3 to 6 and in group C a reduction from 3.4 to 3.3, not statistically significant. The HF index in group C at time T2 presented a significant increase, suggesting a predominance of the parasympathetic nervous system. LF showed a slight increase in T2 and a significant increase in T3 in group B. In group C, the LF showed a significant and progressive increase in T2 and T3 times, suggesting an activation of the sympathetic component (Table 3) [13-17].
Elevation in LF/HF values was observed after spinal anesthesia in group B from 3.3 to 6 and in group C a reduction from 3.4 to 3.3. Statistically none of the results is significant, however, Sakata, in a study involving 45 women undergoing cesarean section, concluded that elevation of LF/HF values equal to or greater than 2 times the initial value after postural change is a predictor of a higher incidence of hypotension after spinal anesthesia . The findings of this study may indicate a protective effect of clonidine as an adjunct to spinal anesthesia in the prevention of hypotension after adjustment of drug doses.
The LF/HF ratio acts as an indicator of the sympatovagal balance . After dispersion of the blockade at T3-T4 levels, the LF/HF ratio practically doubled and returned to baseline when the blockade reached T1-T2. In this case, the sympatovagal balance does not seem to have changed, however, the spectral density test reveals a significant reduction in total power that is not obvious in the isolated LF/HF examination as observed in table 3. Although not statistically significant , there was an increase in LF/HF values after spinal anesthesia in group B from 3.3 to 6 (table 3). Hanss et al 2006, in a study involving 100 patients submitted to cesarean section under spinal anesthesia, found that patients with LF/HF values >2.5 presented a higher risk of hypotension than patients with LF/HF values <2.5 .
Elevation of HF in group C at time T2 suggests a predominance of the parasympathetic with a possible protective effect of clonidine applied in the subarachnoid space. Introna et al 1995 suggests a reduction of sympathetic activity, represented by LF and elevation of parasympathetic activity after spinal anesthesia with bupivacaine, represented by HF, that was not observed in this study, but was found a reduction in HF in group B at time T2. LF showed a slight increase in T2 and a significant increase in T3 in group B. In group C, LF showed a significant and progressive increase in T2 and T3 times (table 3) [13,18-20].
Some studies use linear HRV methods as predictors of hypotension after spinal anesthesia. However, the hypotension associated with spinal anesthesia is the result of several and complex interactions, related to the adaptive capacity of the organism to the perioperative stress. There are reports of cardiorespiratory arrest after installation of spinal anesthesia in young patients, without significant comorbidities. The literature suggests that measures of HRV using linear methods in the frequency domain may predict perioperative hypotension. However, linear methods apparently do not reflect the high complexity of the interactions between the various organic systems in the surgical scenario. Nonlinear methods in the domain of chaos seem to be more appropriate [6-11,19,20].
The time series extracted from biological signals in the vast majority of them present complex and chaotic behavior, and it is not possible to characterize their nature with a single method of analysis. In the analysis of heart rate variability in the chaos domain, the association of 2 or 3 methods reveals a more complex and more representative information of natural events (approximate entropy, Poincaré plot, DFA, correlation dimension, etc.). The joint analysis through 2 or more indexes allows to estimate the complex, regular or random behavior of the time series, bringing to light information and variables not evident by traditional methods . Despite this, the importance and clinical applicability of these new methods has not yet been defined. Sassi et al 2015, in an important review on non-linear indices, considers the new techniques promising. However, it suggests caution in the interpretation of the data and believes that the analysis together with the traditional methods is more adequate while new studies do not appear .
DFA α1 was reduced after spinal anesthesia in both groups; however, it did not present statistically significant difference in any of the groups when comparing moments T3 with T1. However, there is a statistically significant difference between groups B and C at moment T2 with a p of 0.000922, suggesting a reduction in short-term fractal property in group C, which contrasts with the increase in complexity indicated by the increase in approximate entropy and T2 sample entropy in this group. DFA α2 showed no significant difference between groups with an ANOVA showing a p of 0.342388, but student's t identified a p of 0.000201 in T2 between groups B and C, already demonstrating a longer long-term fractality. in group C, different from that observed with DFA α1. This data may suggest a better adequacy of long-term fractality in the analysis of spinal anesthesia patients compared to short-term fracture.
The approximate entropy increased in T2 in group C, when compared to values in T1, but suffered a reduction in group B, which suggests a protective effect of clonidine, however, comparing group C at moments T3 and T1, it was observed a P of 0.0277, with a 95% confidence interval ranging from 8.3220291 to 138.6779709, which is a statistically significant difference and may be suggestive of persistence of sympathetic blockade, not observed in the bupivacaine group.
Sample entropy showed similar behavior to approximate entropy, with T2 elevation in group C, with difference when compared to T2 of group B, with a p of 0.000202, but with reduction in T3 in clonidine group with p of 0, 000954, not significant when comparing T3 and T1 in group B, but with statistical significance in group C analyzing T3 in relation to T1, corroborating the persistence of persistent sympathetic block in group C after the return of motor function identified by the sample entropy.
The effect of clonidine as adjuvant in spinal anesthesia is not yet fully understood. The doses used range from 15 mcg to 150 mcg and there is still no definition of the optimal dose to be used in spinal anesthesia. Also, the dose of the local anesthetic to be administered when it is associated with clonidine is not defined in the literature . Some authors suggest the use of doses above 75 mcg in order to obtain a vasoconstrictive effect through α1 receptors, with a lower vasodilator effect triggered by α2 receptors, where clonidine has greater selectivity. The authors advocating this dose argue that they have a lower incidence of perioperative hypotension .
Although clonidine is an α2 agonist with α2: α1 selectivity of 1:200, and is responsible for triggering hypotension and bradycardia when used intravenously and on the neuroaxis, analysis of the sample in this study demonstrated greater heart rate stability in the clonidine group. than in the bupivacaine group [Figure 3]. This effect may be due to the α2 action of clonidine, which acts both centrally and on the neuroaxis, inhibiting norepinephrine exocytosis and reducing the action of the sympathetic nervous system, which is primarily responsible for increasing heart rate. major hypotension in the clonidine group, consistent with current literature [1,4]. This fact may have been the result of the absence of adjustment of the doses of local anesthetics, since clonidine potentiates the anesthetic effect, allowing the use of smaller doses of anesthetics. In the study, the same dose of isobaric bupivacaine was used in the 2 groups, and in the clonidine group the adjuvant was added, with consequent increase in anesthetic potency, duration and side effects. There is still no definition in the literature of the optimal dose of clonidine to be administered in the intrathecal space, nor of the dose of local anesthetic when adjuvants are associated in the neuroaxis .
The study presents some limitations, considering that the surgical act triggers an individual endocrine metabolic response and variable intensity depending on the surgical aggression. The surgical act itself has the ability to change the heart rate variability, as well as the patient's previous hydration. These factors may influence the final results obtained.
The discharge of PACU after spinal anesthesia is made after the return of the motor function, to the detriment of the other affected neural pathways. Spinal anesthesia provides a sensitive, motor and sympathetic block. This study suggests an extension of sympathetic block in spinal anesthesia, in addition to motor blockade, when clonidine is administered and may indicate a need to review the discharge criteria of the post anesthetic recovery room in patients submitted to surgical procedures under spinal anesthesia, especially when doing use of adjuvants.
At PACU patients are routinely monitored until the return of motor function. They are then discharged and released to the ward where their vital signs are routinely checked every 6 hours. The persistence of sympathetic block after motor recovery and the absence of subsequent continuous monitoring may increase the incidence of adverse events.