Hypotension, with or without bradycardia, occurs in one third of spinal anesthetics (8). This study has demonstrated that a baseline pPD2 of >3.90, an unbiased discriminant obtained from the median value, predicts hypotension after spinal anesthesia for cesarean delivery. If validated, this preliminary finding suggests that a real-time baseline pPD2 measurement could predict and possibly prevent postspinal hypotension.
Pregnant women receiving spinal anesthesia experience autonomic nervous system changes (9–11). The work of Hopf et al. (12) and Gratadour et al. (13) suggests three distinct patterns of response: 1) hypotension and tachycardia, from abolition of sympathetic tone below T4; 2) hypotension and bradycardia, due to parasympathetic tone increased relative to sympathetic tone; and 3) little or no change in hemodynamics. The ability to anticipate those pregnant women likely to experience hypotension would allow clinicians to intervene selectively and early.
The most important observation of this study is that pPD2 predicts postspinal hypotension. Although this pilot study did not test the pPD2 discriminant of 3.90 in a separate, independent population, its selection as the median prespinal pPD2 value adds credibility to the utility of pPD2. Nevertheless, the median value was not prespecified, and only independent confirmation of the predictive value of a pPD2 of 3.90 in another prospective independent cohort can validate its predictive value. Cohorts other than pregnant term women might have different discriminants than 3.90. Alternatively, 3.90 might be robust across many populations.
A much simpler hemodynamic variable, such as baseline heart rate or systolic blood pressure, or a change in arterial blood pressure with position might have predicted postspinal hypotension equally well (23). Table 4 compares the predictive abilities of measured hemodynamic variables in this trial. However, this investigation did not aim to compare various predictors or to find independent predictors—only to examine pPD2.
Participants in this study received 12.5–15 mg of hyperbaric bupivacaine in their spinal anesthetic. In a study comparing spinal bupivacaine 12 and 15 mg, DeSimone et al. (4) found that pregnant women who received the 15-mg dose had, on average, a level of sensory anesthesia 2.2 spinal segments higher than those in the 12 mg group. This study did not assess differences, if any, in the resulting hypotension. However, once the level of sensory block reaches T3-4, sympathetic block is complete. Therefore, we would not expect, nor did we see, a correlation between the dose and incidence of hypotension with the spinal bupivacaine dose range used in this study.
In conclusion, HRV analyzed via pPD2 shows promise as a novel predictor of postspinal hypotension. It stratified patients undergoing cesarean delivery into risk cohorts with 100% sensitivity and 100% specificity. Additional studies are required to validate a pPD2 of 3.9 as a risk discriminant in pregnant women and to identify pPD2 discriminants in other populations. In addition, real-time calculation of this measurement must be developed for this technology to have clinical utility.
Appendix 1: Nonlinear Dimension Analysis
In general, a system that is characterized by n independent variables can be thought of as “residing” in an n-dimensional space (24). The computed dimension would effectively represent the number of active degrees of freedom, a region in phase-space to which all deviating trajectories or perturbations will tend to converge (25). This phase-space “attractor” can be nonintegral, i.e., fractal. Hence, the R-R interval time series can be viewed as a projection line of a trajectory of a newly organized system that is confined by the dimensionality of the attractor. The system dimension can range from 0 to infinity; the lower the number, the simpler the dynamics. In the normal range of physiological response, a dimension of 10 (serving as an upper limit) would resemble white noise. In the intact innervated heart, the HRV dimension was measured to be ∼4, whereas in the Langendorff-perfused isolated heart, the dimension had a metronome-like (∼1) property (19). A decrease in the computed dimension would imply a loss in the number of active degrees of freedom and a decline in the complexity of the R-R series. PD2 offers the advantage of requiring a small data set for analysis of nonstationary signals (15) compared with the classic Grasberger-Procaccia determination of correlation dimension (D2). The point D2 estimate of the correlation dimension was developed by Skinner et al. (7). Like D2, each PD2 reference vector (i.e., the vector for a given R-R interval for a given epoch size of m RR intervals) remains fixed, whereas each of the j vectors (the vector from a given beat to subsequent nonneighboring beats) runs through the entire data series. However, the PD2, j vectors that contribute small log-r values, arises from subepochs with scaling characteristics similar to the surrounding the i vector. Previous studies of HRV have shown that the number of PD2 variables is 4–5 in the general population (19).
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