Heart rate variability assessment to stratify risk of autonomic imbalance during subarachnoid block: A prospective study.

BACKGROUND: Hypotension after subarachnoid block is a common adverse event which can be predicted by simple, safe and indirect measure of autonomic activity. CONTEXT: Heart rate variability has been accepted as an indirect measure of autonomic activity. AIM: It was to evaluate preoperatively risk of hypotension after subarachnoid block. SETTING AND
DESIGN: This is controlled, randomized blind prospective study.
MATERIALS AND METHODS: One hundred adult patients of either sex in the age group of 25 to 60 years belonging to ASA physical status of I to III, scheduled for elective infra-umbilical surgery, were enrolled for this randomized prospective study. During preanesthetic check their HRV was analyzed for time domain and frequency domain parameters. They were classified into two groups of 50 patients each depending on their low to high frequency ratios (LF/HF). Group I included patients with LF/HF <2.5 and Group II included patients with LF/HF >2.5. Sensitivity of LF/HF for prediction of hypotension greater than 20% of baseline was tested. RESULT: The present study showed significant differences of systolic blood pressure (SBP) after subarachnoid block, depending on baseline LF/HF. Patients with low LF/HF showed lowest SBP of 106.08 ± 3.19 (15.22% fall of base line SBP) as compared to high LF/HF which showed 87.62 ± 8.71 (30.26% fall of base line SBP). Baseline LF/HF parameter correlated significantly with proportionate decrease in SBP after subarachnoid blocks. STATISTICAL ANALYSIS: Hemodynamic parameter was analyzed by using student t test on statgraphic version 5.1.
CONCLUSION: Analysis of low and high frequency ratio, reflect autonomic control and may be used as an indirect measure for risk stratification of hypotension after subarachnoid block with high sensitivity.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Subarachnoid anesthesia is commonly used to alleviate pain of surgery as general anesthesia is associated with higher risk of complications. Although subarachnoid block (SAB) is generally well tolerated, hypotension after SAB due to peripheral vasodilatation is a common adverse effect. Intravenous infusion of crystalloids and colloids with prophylactic intramuscular or intravenous vasopressors has proved satisfactory to treat hypotension after SAB in all patients.

Autonomic nervous system modulates systemic hemodynamics through vagal and sympathetic activities which constantly interact to produce variations in heart rate. Differences in the regulation of the autonomic nervous system among patients explain hemodynamic differences in response to subarachnoid block. More recent assessment of cardiac automaticity by a non-invasive, simple and fast method in the form of heart rate variability (HRV) analysis came into existence, which has considerable potential to assess the role of autonomic nervous system (ANS) fluctuations in healthy individuals and in patients with various cardiovascular and non-cardiovascular disorders. Preoperatively its measurement may give prognostic information about hemodynamic changes after SAB.

Pathophysiology of HRV after SAB

Although cardiac automaticity is intrinsic to various pacemaker tissues, heart rate and rhythm are largely under the control of the autonomic nervous system. The normal HRV is due to synergistic action of the sympathetic and parasympathetic components of ANS. An optimum HRV from beat to beat occurs under normal physiological conditions and ranges from no variation to more than 30-beat variation per minute. It reflects individual's capacity to adapt effectively to environmental needs. Time domain analysis reflects parasympathetic activity; while frequency domain analysis, represented by low frequency (LF) and high frequency (HF). emphasizes the balanced behavior of the sympathovagal modulation. LF reflects sympathetic activity of the ANS, and LF/HF reflects relation between sympathetic and parasympathetic function. Hypotension and bradycardia after SAB are mainly due to decreased systemic vascular resistance, caused by inhibition of pre-ganglionic sympathetic nerve fibers and sympathetic innervation of heart. The blockade of pre-ganglionic sympathetic fibers and sympathetic innervations of the heart are associated with a decrease of LF/HF and LF. After subarachnoid block, a decrease of LF and a small increase of HF resulted in a decrease of LF/HF. Prehydration- attenuated sympathetic outflow before SAB in some patients, prevents severe hypotension because changes of the ANS due to SAB are more rapid and pronounced.

We hypothesized that preoperative assessment of autonomic regulation by HRV analysis, will identify patients with risk of hypotension after subarachnoid block, and its analysis may as well identify patients in whom prehydration would be beneficial.

MATERIALS AND METHODS

Selection criteria

After approval from the Ethical Committee of the institution, this randomized prospective study was conducted on 100 adult patients of American Society of Anesthesiologists (ASA) I to III in the age group of 25-60 years of either sex, scheduled for infra-umbilical elective surgery under subarachnoid block. Their pre-anesthetic biochemistry values were within normal limits. Patients with absolute or relative contraindication to subarachnoid block, lumbar spine deformities, lack of sinus rhythm, compromised cardiopulmonary function due to their medication, history of bleeding disorder, history of diabetes and those morbidly obese were excluded from the study. The pre-anesthetic values of heart rate, and systemic blood pressure, along with electrocardiography results and HRV analysis, were recorded. The patients received no premedication and no intravenous fluids before entering the study.

Study population size

Preliminary sample size estimation based on initial pilot observations indicated that approximately 25 patients should be included in each group, in order to ensure power of 0.08 at the 5% significance level for detecting clinically meaningful reduction in heart rate and systemic blood pressure by 20% of base value.

Method of HRV analysis

Heart rate variability was analyzed on Recorder and Medicare System (RMS) Polyrite D data acquisition system with RMS PolyRite Version 2.4 software at steady physiological state in supine relaxed position, limiting body movements, conversations or mental activities; and breathing was controlled and maintained at a rate of 14-16 breaths/min. It was done by an investigator blinded to the hemodynamic changes after subarachnoid block. Short-term HRV analysis was done by 5-minute recordings of fast peaks of R waves on electrocardiogram (ECG) with a sample rate of 1,024 Hz; and beat- to- beat variability of consecutive R waves of sinus rhythm was measured. Data analysis was done for parameters of time and frequency domains. For time domain analysis, the mean interval of consecutive beat- to- beat intervals was determined. The ratio of longest R-R interval to shortest R-R interval was also calculated. Frequency domain analysis was done on Lomb periodogram [Figure 1]. Power spectrum densities were calculated for low frequencies (LF, 0.04-0.15 Hz) and high frequencies (HF, 0.15-0.4 Hz) in normalized units. The ratios of absolute values of LF to absolute values of HF (LF/HF) were calculated. Artifacts were eliminated by computer-based artifact detection, and beats were rejected if they varied by more than 40% from the preceding beat.

Figure 1

Lomb periodogram for computerised calculation of LF, HF and LF/HF ratio

Subarachnoid block, monitoring and measurements

After recording of basal preoperative parameters of heart rate, systemic blood pressure, oxygen saturation and ECG, prophylactic intravenous infusion of 500 mL of ringer lactate solution was started for prehydration. The standardized subarachnoid block (SAB) was performed at interspinous lumbar space L3-L4 with a 25-gauge Quinkce needle in a lateral position under all aseptic conditions. Three milliliters (15 mg) of hyperbaric heavy bupivacaine (0.5%), was injected into the subarachnoid space. The level of sensory block was aimed at T8-T10, tested by pin- prick method. Immediately after injection, patients were positioned supine and oxygen was administered via face mask at the rate of 5 litres/minute.

Base-line blood pressure and heart rate were recorded preoperatively. After subarachnoid block, 5 different time-events were defined for hemodynamic measurements: time1: base-line (BL), time2: post- hydration (PH), time3: 5 minutes after SAB (SAB + 5), time4: 15 minutes after SAB (SAB +15) and time5: 45 minutes after SAB (SAB+45). Hypotension was defined as SBP less than 80% of baseline.

Group assignment

A total of 100 patients were classified prospectively into two groups of 50 patients each according to the LF/HF ratio. Group I included patients with LF/HF ratio <2.5; and group II, patients with LF/HF ratio >2.5.

In all patients, hypotension and bradycardia were treated by α1 agonist vasopressor mephentermine (IV/IM intravenous/intramuscular) and atropine in a standardized manner. Fall in SBP to within 20% of baseline was treated with controlled infusion of ringer lactate solution. Decrease of SBP below 80% of baseline required rapid infusion of ringer lactate solution; and if SBP persisted below 80% of baseline despite infusing ringer lactate solution, intravenous bolus of vasopressor mephentermine 6 mg was added to infusion regime. The total amount of vasopressor was analyzed for both groups. Blood loss was replaced by infusing blood. All patients stayed in the post-operative recovery room and were monitored until subarachnoid block regressed completely.

Statistics

The quantitative data obtained was analyzed and compared for the two groups by applying t test on statgraphics-plus version 5.1. P <0.05 was considered statistically significant.

RESULTS

All the 100 enrolled patients scheduled to undergo infra-umbilical elective surgery under subarachnoid block completed the study according to protocol. They were evaluated for heart rate variability on RMS PolyRite D; and at preoperative level, HF was significantly lower in the group II ( with LF/HF >2.5 ) compared to group I (with LF/HF <2.5) [Table 1].

Table 1

HRV data analysis (mean±SD)

The groups were compared with respect to demographic data for age, weight, sex, ASA physical status, level of sensory block and amount of local anesthetic [Table 2]. Pre-anesthetic laboratory values of all patients were within acceptable normal limits. No difference was found between groups at base-line.

Table 2

Characteristics of patients under study

Prehydration of patients did not affect the base-line SBP in either group, but they demonstrated significant differences in SBP after SAB depending on LF/HF at base-line. The lowest SBP recorded in the low LF/HF group (group I) remained significantly higher than that of high LF/HF group (group II), i.e., 106.08±3.19 mm Hg versus 87.62±8.71 mm Hg, respectively. A significant decrease in SBP, viz., of 30%, was found in the group II between the first time-event (at BL) (125.64±8.48 mm Hg) and the fifth time-event lowest (87.62±8.71 mm Hg) [Table 3]. Group I of low LF/HF patients required vasopressor intervention in 3 (6%) patients only, which may be attributed to their old age; whereas in the group II, a mean of 10 mg of vasopressor was given to restore blood pressure to 80% above the base value [Figure 2].

Table 3

Hemodynamic parameters (mean±SD) and statistical analysis for the two groups

Figure 2

Graph depicting number of patients treated for hypotension by either iv fluid alone or iv fluid with vasopressor

Base-line LF/HF of all patients was significantly correlated to the percentage decrease in arterial blood pressure after subarachnoid block, while established predictors heart rate and arterial blood pressure did not correlate with the degree of hypotension. No perioperative complications except hypotension were recorded in any patients.

DISCUSSION

The last two decades have witnessed the recognition of a significant relationship between autonomic nervous system and cardiovascular mortality. Heart rate variability, the amount of change from the mean value of heart rate, is a valuable investigative tool that provides information about the sympathetic-parasympathetic balance and its influence on the cardiorespiratory physiology. Cardiac function is mainly controlled by vagal mechanism.[1] The clinical importance of HRV became appreciated when it was confirmed that HRV was a strong independent predictor of mortality after an acute myocardial infarction, due to its ability to provide insight into physiological and pathological conditions.[23] Besides post-infarction, a reduction in HRV has been reported in several neurological disorders, including diabetic neuropathy, brain damage, the Guillain-Barre syndrome, and uremic neuropathy.[45] Autonomic nervous system can modulate hemodynamic parameters, including SBP and HR.[6]

Autonomic nervous system can be evaluated by computer-based HRV processing for either time domain (R-R interval) or frequency domain (power spectral density measurements for low and high frequencies). The latter employs periodogram, which is considered superior to fast Fourier transform (FFT) for power spectral density estimation.

Estimated LF/HF reflects balance of autonomic nervous system. LF, which is partially affected by parasympathetic activity, mainly indicates vasomotor activity, an indirect index of sympathetic nervous system; while HF suggests vagal nerve response.[78] In our prospective study, heart rate variability was analyzed in 100 patients scheduled to undergo elective infra-umbilical surgeries under subarachnoid block. Although at baseline and post-hydration, both the groups had comparable blood pressure recordings prior to induction of SAB, yet this was not maintained after SAB. The patients with high LF/HF (>2.5) ratio had developed severe hypotension after SAB.

Time domain (R-R interval) parameters reflect vagal regulation; therefore, frequency domain analysis, especially the LF/HF ratio, is considered more sensitive for prediction of hypotension after SAB compared with parameters solely reflecting parasympathetic control.

Frolich et al. in 2002 demonstrated that baseline HR and SBP may indicate the risk of hypotension after spinal anesthesia in prehydrated obstetrical patients.[9] Hence these parameters were considered in our study. Different levels of LF/HF, which reflects sympathovagal balance, correlated with comparable baseline hemodynamic parameters prior to and after induction of SAB. Patients with high LF/HF ratio at BL before prehydration were at high risk of hypotension after SAB. These findings suggest that LF/HF and LF may be indirect measures of the sympathetic activity of the ANS regulation. In contrast, patients showing low LF/HF ratio and LF along with increased HF, developed only minor changes in hemodynamic parameters after SAB.

Total HRV is reduced in elderly persons and patients suffering from illness related to myocardium or neuropathy. Effect of age on HRV can be observed in childhood.[10] Twenty-year-old individuals often show a swing of 20 or more between the high and low points in their heart rates. Persons over 50 years often show changes of 10 beats or less. Ageing is also associated with alterations in vascular reactivity, which manifest clinically as exaggerated changes in systemic blood pressure, hypertension and/ or orthostatic hypotension. Persons who are physically active show a wider range between maximum and minimum heart rate. Depressed HRV is a predictor of mortality and arrhythmic complications, which is independent of other recognized risk factors.

Studies in pregnant patients scheduled for elective cesarean section have demonstrated high predictive value of HRV on hypotension after subarachnoid block.[11] HRV analysis may be superior compared with baseline HR or SBP for risk stratification of hypotension after subarachnoid block as it is based on measuring the beat- to- beat interval of sinus rhythm, influenced by volume status, respiration, intrathoracic pressure and baroreceptor reflexes. The impaired parasympathetic activity, reflected by HF, indicated a high risk of hemodynamic instability. Baseline LF/HF of 2.5 may be a cut off value suitable to detect patients at risk of hypotension after SAB, not the baseline HR or SBP of the patients.

Purpose of HRV analysis as a diagnostic modality to optimize routine anesthetic care in patients whose surgery is being planned under SAB is to improve hemodynamic stability intraoperatively with prophylactic treatment. Measurement of HRV is clinically simple and based on normal electrocardiographic recordings, and commercial tools offer a computerized interpretation.

CONCLUSION

HRV has considerable potential to assess the role of ANS fluctuations in healthy individuals and in patients with various cardiovascular and non cardiovascular disorders. Its analysis with low- to high-frequency ratio before subarachnoid block should be used as an indirect measure for risk stratification of hypotension.

Invasive direct measures of autonomic control are not possible to implement in a clinical setting. Analysis of HRV is a noninvasive and indirect measure to assess autonomic regulation in high- risk patients: it would indicate the need for intensive monitoring and perhaps prophylactic treatment.

HRV analysis prior to SAB provides a perspective of the role of ANS in predicting hypotension and intervention strategy. HRV is a key indicator of an individual's cardiovascular status.