Long-Term Continuous Heart Rate Variability Monitoring Over 20 Days for Severe Tetanus: A Case Report

Introduction

Tetanus is a highly lethal infectious disease caused by the gram-positive anaerobic bacterium Clostridium tetani, which is prevalent worldwide. The main symptoms include trismus, convulsions, generalized muscle rigidity, severe dysphagia, and muscle spasms. C. tetani releases a potent neurotoxin that binds to presynaptic membranes at neuromuscular junctions and to sympathetic adrenergic neurons at central excitatory synapses, resulting in motor and autonomic nervous system impairment. Severe tetanus is characterized by autonomic nervous system dysfunction, including sudden hypertension, tachycardia, arrhythmias, and tachypnea, all of which can worsen the prognosis [1]. Autonomic dysfunction in severe tetanus remains difficult to identify objectively, even with current intensive care methods.

Heart rate variability (HRV) has become a widely recognized indicator of autonomic function [2]. HRV is defined as a slight, periodic variation in the interval between heartbeats. Heart rate and blood pressure oscillations are classified into 3 frequency bands: very low frequency (0.003–0.04 Hz), low frequency (LF; 0.04–0.15 Hz), and high frequency (HF; 0.15–2.0 Hz). HRV-LF reflects both sympathetic and parasympathetic activity, HRV-HF represents parasympathetic activity alone, and the HRV-LF/HF ratio indicates sympathetic activity [3,4]. HRV has been used to assess autonomic nervous system function in various disorders that affect autonomic regulation, including cardiovascular diseases and sepsis. Multiple studies [5–7] have utilized HRV analysis to examine autonomic dysfunction in cases of severe tetanus; however, these investigations were limited to short-term HRV recordings, typically ranging from 5 min to 24 h.

In this report, HRV was continuously measured and recorded for 22 days during the intensive care unit (ICU) stay of a patient with severe tetanus (Ablett classification grade 4). Throughout the monitoring period, we assessed whether long-term HRV measurements were associated with the patient’s autonomic dysfunction.

Case Report

DIAGNOSIS AND TREATMENT COURSE:

A diagnosis of tetanus was made, and the patient was placed on mechanical ventilation with ICU management. Generalized tonic convulsions and a rapid increase in blood pressure were observed on the first day of hospitalization. Sedative agents (midazolam, propofol, and dexmedetomidine) and magnesium sulfate were administered; rocuronium was added when convulsions could not be controlled. Electroencephalographic monitoring was not performed because the condition was not considered an epileptic seizure given the concurrent use of 3 sedatives. When blood pressure increased, intravenous nicardipine and landiolol were administered to stabilize circulatory control. Tetanobulin and metronidazole were also administered for tetanus treatment.

On the 25th day of hospitalization, sedative administration was discontinued because the seizures had ceased. However, on the 26th day, generalized tonic seizures recurred, and the patient’s blood pressure again became unstable. On the 31st day of hospitalization, the sedative was discontinued again. The seizures and rapid blood pressure fluctuations subsequently resolved. On day 37 of hospitalization, the patient was successfully weaned off the ventilator and discharged from the ICU (Figure 1).

MEASUREMENT METHOD:

Heart rate and blood pressure were measured on the first day of admission using a percutaneous electrocardiogram monitor and an intravascular arterial pressure monitoring catheter placed in the radial artery.

From day 12 to day 33 of hospitalization, heart rate waveforms and vital signs were documented using a CSM-1901 bedside monitor (Nihon Kohden, Tokyo, Japan). Data were continuously recorded and stored on a PRM-7400 critical care ward support system (Nihon Kohden) for 24 h, after which the waveforms were extracted. The extracted waveforms were analyzed using a Fluclet circulatory parameter analysis device (Dainippon Sumitomo Pharma Co., Ltd., Tokyo, Japan), and HRV was calculated by frequency analysis of the interval between heartbeats.

Fluclet uses wavelet-based frequency analysis. The LF and HF spectra were calculated as frequency analysis indices of HRV. Based on these results, LF/HF ratios were subsequently determined.

HEART RATE VARIABILITY MEASUREMENT RESULTS: The numbers of HRV-LF and HRV-LF/HF spikes during hospitalization are displayed in Figure 2.

The frequencies of systolic blood pressure and HRV spikes showed similar fluctuation patterns. From days 12 to 23 of hospitalization, HRV spikes occurred as often as 8 times per day but began to decrease from day 24 onward. On day 25, when the patient’s muscle spasms were considered resolved, no spikes were recorded. However, when spasms recurred, spikes were again observed at a frequency of approximately 2 per day.

Discussion

This patient was diagnosed with severe tetanus (Ablett classification grade 4) due to the presence of autonomic dysregulation and increased sympathetic tone during the acute phase of the disease.

Several reports of autonomic dysfunction in tetanus have been published. Goto et al [5], Duong et al [6], and Hai et al [7] attempted to diagnose autonomic dysfunction by measuring HRV over 24 h and 5 min, respectively. Their findings indicated that HRV may reflect functional impairment of the autonomic nervous system in tetanus and may serve as a valuable diagnostic tool. In the present case, HRV recording and retrospective analysis were conducted with the expectation that they would enhance understanding of the clinical course of autonomic dysfunction. However, no previous studies have involved long-term monitoring of autonomic nervous system disturbances in tetanus over a period of 20 days or more, nor have they demonstrated a relationship between blood pressure fluctuations and temporal changes in HRV spikes.

By continuously measuring HRV over an extended period, we confirmed that the frequency of systolic blood pressure spikes was strongly associated with changes in HRV-LF and HRV-LF/HF spike frequencies, as shown in Figure 2. These findings suggest that the frequency of HRV spikes in severe tetanus reflects the degree of autonomic impairment and that both sympathetic and parasympathetic functions may be affected by tetanus-induced autonomic dysfunction. Although no real-time HRV analysis method is currently established, if such technology becomes available, it may be useful for predicting the progression of severe tetanus.

Conclusions

Long-term (20-day) continuous HRV measurements were conducted in a case of severe tetanus with autonomic dysfunction. A link was observed between the frequency of systolic blood pressure spikes – an autonomic symptom – and the frequency of HRV spikes. The relationship between HRV fluctuations and blood pressure variability may aid in diagnosing severe tetanus and autonomic nervous system dysfunction, as well as predicting disease progression. In the future, when real-time HRV analysis methods are established, further studies will be needed to determine whether HRV monitoring can reliably assess the severity of autonomic nervous system dysfunction among patients with severe tetanus.