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ORIGINAL ARTICLE
Year : 2022 | Volume
: 70
| Issue : 8 | Page : 269-275
Preoperative Heart Rate Variability Predicts Postinduction Hypotension in Patients with Cervical Myelopathy: A Prospective Observational Study
Sarah L Boyle1, Alastair Moodley1, Emad Al Azazi1, Michael Dinsmore1, Eric M Massicotte2, Lashmi Venkatraghavan1
1 Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Toronto, Canada
2 Division of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Canada
Correspondence Address:
Lashmi Venkatraghavan
Department of Anesthesia, University of Toronto, Toronto Western Hospital, University Health Network, 399 Bathurst St, Toronto, ON, M5T 2S8
Canada
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/0028-3886.360911
Background: Autonomic dysfunction, commonly seen in patients with cervical myelopathy, may lead to a decrease in blood pressure intraoperatively.
Objective: The aim of our study is to determine if changes in Heart rate variability (HRV) could predict hypotension after induction of anesthesia in patients with cervical myelopathy undergoing spine surgery.
Methods and Material: In this prospective observational study, 47 patients with cervical myelopathy were included. Five-minute resting ECG (5 lead) was recorded preoperatively and HRV of very low frequency (VLF), low frequency (LF), and high frequency (HF) spectra were calculated using frequency domain analysis. Incidence of hypotension (MAP <80 mmHg, lasting >5 min) and the number of interventions (40 mcg of phenylephrine or 5 mg of ephedrine) required to treat the hypotension during the period from induction to surgical incision were recorded. HRV indices were compared between the hypotension group and the stable group.
Results: The incidence of hypotension after induction was 74.4% (35/47) and the median (IQR) interventions needed to treat hypotension was 2 (0.5–6). Patients who experienced hypotension had lower HF power and higher LF–HF ratios. A LF/HF >2.5 indicated postinduction hypotension likely. There was a correlation between increasing LF–HF ratio and the number of interventions that needs to maintain the MAP above 80 mmHg.
Conclusion: HF power was lower and LF-HF ratio was higher in patients with cervical myelopathy who developed postinduction hypotension. Hence, preoperative HRV analysis can be useful to identify patients with cervical myelopathy who are at risk of post-induction hypotension.
Keywords: Cervical myelopathy, general anesthesia, heart rate variability, hypotension
Key Message: This prospective observational study showed that preoperative heart rate variability (HRV) measurement can be useful to identify patients with cervical myelopathy who are at risk of postinduction hypotension.
Cervical myelopathy (CM) is a condition where cervical spinal cord is compressed causing dysfunction of motor, sensory, and sphincter functions. Patients with CM often require decompression of spinal cord with or without fusion of the spine either through an anterior or a posterior approach. Maintaining an adequate spinal cord perfusion during the surgery is an important consideration in these patients to prevent postoperative neurological deficits. Based on the evidence from acute spinal cord injury management, it has been suggested that maintaining a mean arterial pressure (MAP) >80 mmHg intraoperatively can reduce the risk of secondary neurological injury during cervical spine surgeries.[1],[2] Importantly, up to 51% of patients with moderate to severe CM manifest autonomic dysfunction[3] and the presence of autonomic dysfunction may increase the risks of hypotension intraoperatively.[4]
Among various monitoring methods, heart rate variability (HRV) has been used to detect autonomic dysfunction associated with many conditions.[5],[6],[7] HRV consists of both low (0.04–0.15 Hz) and high (0.20–0.40 Hz) frequency components.[8],[9] High-frequency variability reflects changes solely to the parasympathetic modulation, whereas low-frequency variability reflects changes to both the parasympathetic and the sympathetic modulation.[8],[10],[11] Interestingly, preoperative HRV has been shown to predict the development of hypotension after administration of both general or spinal anesthesia and can be a useful screen tool to predict hypotension in patients with risk of autonomic dysfunction.[4],[12],[13],[14],[15],[16],[36]
Therefore, the aim of our study was to determine if HRV analysis is useful in predicting the development of hypotension after induction of general anesthesia in patients with CM undergoing cervical decompression and fusion procedure.
Materials and Methods
This is a prospective, single-center, observational study of consecutive patients (aged 18–70 years) undergoing elective anterior or posterior cervical decompression and fusion for degenerative CM in our institution during the period from Sept 2017 to June 2018. The institutional research ethics board approved the study (REB# 14-8164-BE) and written informed consents were obtained from all patients. Exclusion criteria were patient refusal, complete spinal cord injury, posttraumatic myelopathy, patients at risk for autonomic neuropathy (diabetes, end-stage renal disease, and Parkinson's disease), resting tachycardia (heart rate >100 bpm), atrial or ventricular arrhythmia, and second- or third-degree heart block.
Preoperative ECG recordings
Preoperatively, on the day of surgery, all study patients had standardized 5-lead electrocardiogram (ECG) recording for 5 min using a Datex-Ohmeda S5 Monitor (GE Healthcare, Finland). ECG recording were done in a quiet room while patients were lying supine and breathing normally. The ECG was recorded directly onto a computer using custom software (s5 collect, Datex-Ohmeda Division, GE Healthcare, Finland). In addition, baseline heart rate (HR) and non-invasive blood pressure (BP) were also recorded prior to ECG recording.
Anesthesia management
Anesthesia induction and maintenance was as per our institutional standard practice. After establishing intravenous access, 500-ml balanced salt solution was administered over 20 min. Prior to induction, Canadian Anesthesiologists Society standard monitors (5-lead ECG, pulse oximetry, capnography, and non-invasive blood pressure) were applied on all patients. In addition, an arterial line was also inserted immediately after induction. Anesthesia was induced with propofol (1.5 mg/kg over 60 seconds), fentanyl (1–2 mcg/kg), and rocuronium (0.1 mg/kg). Depth of anesthesia was monitored using an entropy monitor (GE Healthcare, Finland). Intubation was performed after the loss of response to train-of-four as well as a decrease in state entropy (SE) value less than 50. Anesthesia was maintained on inhalational anesthesia [sevoflurane in oxygen-air (1:1 l/min)], titrated to SE values between 40 and 50 in all patients except in patients undergoing intraoperative transcranial motor-evoked potential monitoring where total intravenous anesthesia [infusions of propofol (75–125 mcg/kg/min) and remifentanil (0.05–0.125 mcg/kg/min)] was used.
Hypotension and intervention to treat events
The study period was from induction of anesthesia to surgical incision. Our institutional practice is to maintain all patients with CM with an intraoperative MAP target of >80 mmHg. Hypotensive episodes (MAP <80 mmHg, lasting >5 min) were managed with either phenylephrine and/or ephedrine boluses. All episodes of hypotension and the number of interventions to treat these episodes during the period from the induction of general anesthesia to the surgical incision were recorded. An intervention to treat hypotension was defined as a bolus of 40 mcg phenylephrine or 5 mg ephedrine. All blood pressure values in the study were recorded from the non-invasive blood pressure cuff cycling every 2.5 min to maintain consistency.
HRV analysis
HRV analysis was performed postoperatively by one of the authors (SB) and electronic recordings were downloaded for offline analysis. The ECG recordings (Lead II) were first analyzed manually to confirm the sinus rhythm. Data were then transferred to custom software (LabChart 8 Software, AD Instruments, Colorado Springs, CO, USA) and frequency domain analysis of HRV was performed. Prior to analysis, the software analyzed the data for the presence of ectopic activity (>2% of the recording) and if present, then the data was excluded for HRV analysis. Frequency domain parameters were used as they are more reliable with a short 5-minute ECG recording compared to time domains.[15] Three frequency domain parameters that were measured include very low frequency (VLF) (<0.04 Hz), low frequency (LF) (0.04—0.14 Hz), and high frequency (HF) (0.15—0.4 Hz). Total power (TP) and power of individual spectral component (VLF, LF, HF) were calculated by LabChart8 using the Lomb-Scargle Periodogram technique and expressed in ms2. The ratio of LF to HF was calculated and expressed as LF/HF. HRV analysis followed the standards suggested by the Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology in 1996.[17] HRV indices of interest in this study were TP, power of LF, HF, and LF/HF ratio.
Data analysis
Patients were divided into two groups depending on the presence or absence of hypotension: those who required treatment with vasopressors (phenylephrine or ephedrine) to maintain MAP >80 mmHg during the time from induction of anesthesia to surgical incision (hypotension group) versus those who required no interventions to maintain MAP >80 mmHg (stable group).
The primary outcome was to determine the differences in HRV indices (TP, VLF, LF, HF, and LF/HF ratio) between the hypotension group and stable group. Secondary outcome measures include (i) correlation between HRV indices and number of interventions needed to keep MAP >80 mmHg and (ii) correlation between HRV indices and preoperative MAP, HR, and the severity of myelopathy (mild, moderate, and severe as per modified Japanese Orthopaedic Association Scale[18]).
Statistical analysis
As this is an observational study, we planned to recruit 60 patients to provide adequate sample size in line with previous studies.[11],[19] Previous studies have shown that among the HRV variables, TP and LF/HF ratio (>2.5) were the common variables that were predictors of hypotension after both general and spinal anesthesia.[13],[16],[20] Hence, we chose LF/HF ratio >2.5 as a cut off value as a predictor of hypotension for this study. Data were presented as either n (%) or Median [interquartile range (IQR)] as indicated. Normality of distribution was performed using Kolmogorov–Smirnov test and only the demographic and anesthesia data were normally distributed. Comparisons between groups were made using Fisher's exact test for categorical variables (Gender, severity of myelopathy, method of anesthesia, surgical approach) and the Mann–Whitney U test for continuous variables (age, anesthetic data, and HRV indices). We used Mann–Whitney U test for all the analysis due to unequal group size and small group size. Pearson's correlation analysis was used to examine the relationship between HRV indices and the number of intervention to treat hypotension, preoperative MAP, HR, and severity of myelopathy. Statistical analysis was done using IBM SPSS Statistics for Windows, version 25 (IBM Corp., Armonk, N.Y., USA).
We followed the STROBE guidelines for the reporting of observational studies.[21]
ResultsIn total, 65 patients were recruited for the study and 18 patients were excluded [Figure 1]. Thus 47 patients [29.8% female; median (IQR) age 54 (46–63) years] were included for final analysis [Table 1]. Majority of patients (37/47; 78.7%) had mild CM and the remainder (10/47; 21.3%) had moderate myelopathy. There were no patients in the severe category. About 61.7% (29/47) of patients had anterior cervical decompression and fusion, and the rest (18/47; 38.3%) had posterior cervical decompression and fusion.
The incidence of hypotension after induction was 74.4% (35/47) and the median (IQR) interventions needed to treat hypotension was 2 (0.5–6). Patient demographics were similar between the hypotension group and stable group except for the severity of myelopathy [Table 1]. Similarly, there were no differences between the groups regarding doses of anesthetic agents as well as type of anesthesia (TIVA vs. Inhalational) [Table 1].
The results of the HRV indices are shown in [Table 2]. There was a trend towards lower total power in the hypotension group when compared to stable group but this was not statistically significant [1374 (637.9-3130.5) vs. 2191 (1258.5-2577) ms2; P = 0.26; Mann–Whitney U test]. Similarly, powers of individual spectra (VLF, LF, and HF) were also trending lower in the hypotension group when compared to stable group; however, only HF power difference was statistically significant [117.3 (73.2-430.8) vs. 350.4 (197.2 -520.5) ms2; P = 0.02; Mann–Whitney U test]. Similarly, LF/HF ratio was significantly higher in hypotension group when compared to stable group [3.2 (1.9-4.4) vs. 1.2 (0.8-1.8), P < 0.001; Mann-Whitney U test]. A LF/HF > 2.5 indicated postinduction hypotension was likely (p = 0.04, Fisher's Exact test). Furthermore, there was a correlation between increasing LF/HF ratio and the numbers of interventions that needs to maintain MAP above 80 mmHg (Pearson's correlation r = 0.44, P = 0.001) [Figure 2].
Table 2: Differences in HRV indices between hypotension group and stable group
Figure 2: Correlation between the number of interventions needed to maintain MAP >80 mmHg and HRV indices. Figure showing correlation between the number of interventions to keep MAP >80 mmHg and TP (a), HF power (b), LF power (c), LF/HF ratio (d). There was a correlation between increasing LF/HF ratio and the numbers of interventions that needs to maintain MAP above 80 mmHg (Pearson's correlation r = 0.44; P = 0.001). MAP – mean arterial pressure TP = total power, LF- low frequency, HF-high frequency, LF/HF- low frequency: high frequency ratioWith regards to correlation analysis, only LF shows a weak correlation with the preoperative HR (Pearson's correlation r = 0.37; P = 0.009) [Figure 3]. There was no relationship between any HRV indices and preoperative MAP or severity of cervical myelopathy.
Figure 3: Correlation between preoperative heart rate and HRV indices. Figure showing correlation between the preoperative heart rate and TP (a), HF power (b), LF power (c), LF/HF ratio (d). There was a correlation between the preoperative heart rate and LF power (Pearson's correlation r = 0.37; P = 0.009). TP = total power, LF- low frequency, HF-high frequency, LF/HF- low frequency: high frequency ratio Discussion This study looked into the utility of preoperative HRV in identifying patients with cervical myelopathy who may be at risk of hypotension after induction of anesthesia. Our study demonstrated that HF power was significantly lower and LF/HF ratio was higher in patients who needed interventions to keep MAP >80 mmHg compared with patients who did not.[37] Better ability to predict which patients with CM are likely to develop hypotension post induction would enable the anesthesiologist to tailor their anaesthetic technique to avoid episodes of hypotension. This could be achieved by reducing anaesthetic doses at induction and/or earlier use of vasopressors and fluid resuscitation.
Patients with spinal cord injury (SCI) often manifest autonomic dysfunction in the form of neurogenic shock, autonomic dysreflexia, orthostatic hypotension, cardiac arrhythmias, gastrointestinal and genitourinary dysfunctions.[22],[23],[24],[38],[39] Recently, a system of documenting autonomic dysfunction in SCI has been proposed by the American Spinal Injury Association and the International Spinal Cord Society.[25] However, autonomic function testing in patients with compressive CM is still limited.[40] Though there are many studies that looked into HRV in patients with spinal cord injury,[26],[27],[28],[29],[30],[31] very few studies evaluated the role of HRV in patients with CM.[3] Srihari et al.[3] have shown that HF and TP are increased in patients with CM compared to matched controls. It has been shown that patients with cervical SCI have reduced VLF and LF power reflecting a reduction in sympathetic outflow.[26] The LF/HF ratio in this population is unclear with studies showing that it either remains stable[4],[22] or is decreased.[26],[27],[28],[31]
Two HRV indices that reflect autonomic dysfunction and are predictive of hypotension under anesthesia are the TP and LF–HF ratio. Mazzeo et al.[7] demonstrated that patients undergoing general surgery with a preoperative TP of <500 ms2 are more likely to develop hypotension during general anesthesia. Hanss et al.[13] and Bishop et al.[16] both found that LF/HF >2.5 and 2 is associated with a higher incidence of hypotension after spinal anesthesia in the obstetric population. In our study, there was a trend towards lower total power in the hypotension group, but this was not statistically significant. However, LF/HF ratio was significantly higher in hypotension group when compared to stable group, which is consistent with previous studies.
Different techniques are available for HRV analysis. Frequency domain analysis is useful for shorter recordings (<5 min) of ECG and time domain analysis are often used for longer recordings (>18 hours).[9],[17],[32] Among the HRV indices, it has been shown that parasympathetic activity is a major contributor of HF power.[9],[10],[17],[32] However, the source of LF power is not clear.[8],[10],[17] LF power may be produced by both the parasympathetic and sympathetic activity, and also the blood pressure regulation via baroreceptors.[8],[10] Which of these parameters contributes most to LF power is determined by what the patient is experiencing at the time of the recording.[8] Shaffer et al.[33] found that when the LF is calculated under resting conditions, as in our study, baroreflex activity has more influence than sympathetic activity.
In our study, why patients with a LF/HF ratio >2.5 were more likely to develop perioperative hypotension may be explained by two possible hypotheses. Firstly, the LF power in our cohort may be produced predominantly by the baroreflex activity and not the sympathetic activity. Hence, a high LF/HF ratio indicates higher resting parasympathetic tone and therefore impaired sympathetic response at induction. Alternatively, the stress of impending surgery with marked increases in sympathetic activity might be a major contributor of the LF power and a higher LF/HF ratio. The higher tendency for these patients to develop hypotension may reflect their inability to further increase their sympathetic drive to compensate for the vasodilatory effects of general anesthesia.
Our study has many limitations. Firstly, this is an observational study with a small sample size. As there are no previous studies in this population it was very difficult to calculate the sample size that is adequately powered. We assumed that that the incidence of hypotension would be around 50%. However, our study showed that incidence of hypotension was 75%. The high rate of hypotension among our cohort despite the majority of patients having mild myelopathy may reflect that even patients with mild symptoms, might have subclinical autonomic dysfunction as indicated by changes in HRV indices. Hence, there is a need for further studies in patients with CM.
Secondly, our study population is quite heterogeneous with varying severity of myelopathy that is probably reflected in the variations in HRV indices. In addition, there is a lack of standardized anesthetic technique as some patients received TIVA to facilitate intra-operative neuromonitoring. The hemodynamic effects of propofol/remifentanil and sevoflurane can be quite different. However, there were no differences between the groups regarding type of anesthesia [Table 2]. Similarly, when we reanalyzed the data after removing TIVA patients, the statistically significant differences between the groups for both HF [120.2 (86 -430.8) vs. 300.8 (91.5-456.4) P = 0.05; Mann–Whitney U test] and LF/HF ratio [3.3 (1.9-4.4) vs. 1.1 (0.7 -1.8) P < 0.001; Mann–Whitney U test] were still present. Similarly, being an observational study, we included all consecutive patients with CM in the study and hence our cohort consists of patients undergoing both anterior and posterior surgical approaches. Compared to anterior approach, posterior cervical decompression and fusion does add additional confounders such as longer induction to incision time as well as hemodynamic effect of prone position. We did analyze the data after eliminating the prone-position cases. Though the sample size has reduced significantly, LF/HF ratio was still significant between the groups, whereas the number of interventions between the anterior and posterior cases was not significant. Median (IQR) interventions for anterior and posterior cases were 3.1 (1-7) and 2.9 (0-6). Hence, this study should be considered as a pilot study that can help design adequately powered studies.
Finally, our study was restricted to hypotension postinduction and did not examine the incidence of hypotension during the entire case. This was in order to try to minimize intraoperative factors that might have also produced hypotension and confounded our results. In addition, in our study preoperative MAP in the hypotension group was lower than the stable group. However, this was not statistically significant (p = 0.06). Though it is possible that preoperative MAP might have a role in our results, we cannot confirm it with unequal groups with small number of patients.
ConclusionsOur prospective observational study showed that among the HRV indices, high-frequency spectral power was lower and LF–HF ratio was higher in patients with CM who developed postinduction hypotension when compared to those who had stable hemodynamics. LF/HF ratio >2.5 can be associated with an increased risk of hypotension postinduction. Therefore, preoperative HRV analysis can be useful to identify patients with CM who are at risk of postinduction hypotension. This can be useful for anesthesiologist to pre-emptively adjust their anesthetic technique to reduce the incidence of hypotension and risk of secondary neurological injury in this population.
Financial support and sponsorship
This study was supported by the Department of Anesthesia, Toronto Western Hospital, University of Toronto.
Conflicts of interest
There are no conflicts of interest.
References
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