Risk factors for vasovagal reaction associated with cerebral angiography via femoral catheterisation

Abstract

Objective

To analyse the related risk factors for vasovagal reaction associated with cerebral angiography via femoral catheterisation and discuss treatment measures and prevention and control methods.

Methods

The data of 3107 patients on whom cerebral angiography was performed in two high-volume interventional neuroradiology centres within 8 years were retrospectively analysed. Patients were divided into the vasovagal reaction and non-vasovagal reaction groups according to whether vasovagal reaction developed. The two groups’ clinical data were analysed using univariate and multivariate logistic regression analysis to examine vasovagal reaction-related factors.

Results

Of the 3107 patients included, 127 developed vasovagal reaction (4.09%). Of the 127 patients who developed vasovagal reaction, 123, three and one had vasovagal reaction after sheath removal, during cerebral angiography and upon femoral artery compression device removal, respectively. Differences in age, body mass index, sex ratios, proportions of patients with hypertension, diabetes and hyperlipemia, and adoption rate of femoral artery compression device were not statistically significant between the two groups (P > 0.05). Compared with the control group, the vasovagal reaction group had a significantly longer preoperative fasting time (P < 0.05). Multivariate logistic regression analysis revealed preoperative fasting time as the only risk factor for vasovagal reaction that was associated with cerebral angiography (P < 0.001).

Conclusion

Excessive fasting time before cerebral angiography is the most important risk factor for vasovagal reaction associated with cerebral angiography.

Introduction

Vasovagal reaction (VVR) is an abnormal autonomic imbalance that is mediated by the vagus nerve. It is caused by many factors, such as pain, disgust, hunger, heat, certain medical and surgical procedures, imagined or real exposure to bodily harm, the sight of blood, cardiac spasm, visceral distention and pleural or peritoneal irritation.^1–3 VVR is most commonly characterised by hypotension followed by paradoxic bradycardia. Its signs and symptoms include lightheadedness, weakness, nausea, vomiting, yawning, sighing, impaired hearing, urinary urgency, unsteadiness, diaphoresis, mydriasis and pallor.¹ VVR is an unexpected high-risk condition that can cause irreversible harm to patients without timely treatment.^4–6 Coronary and cerebral angiography can induce VVR, and there are numerous reports of cardiovascular interventions being complicated by VVR.^1,4–9 However, only a few reports exist on interventional neuroradiology procedures being complicated with VVR,¹⁰ possibly because the incidence of VVR in patients undergoing interventional neuroradiology procedures is lower than that in those receiving cardiac interventional therapy. However, interventional neuroradiologists might not understand VVR and may neglect such conditions. The incidence of VVR associated with interventional neuroradiology procedures is low;¹⁰ however, its acute onset might have severe consequences if not treated appropriately or in time. VVR may be fatal in severe cases; therefore, sufficient attention should be paid to it. The purpose of this study is to explore the risk factors of VVR associated with cerebral angiography to provide evidence for its prevention and control.

Materials and methods

Study subjects

This retrospective multicentre project was approved by the Institutional Review Board of Beijing Chaoyang Hospital and the Institutional Review Board of Bayi Brain Hospital affiliated with Beijing PLA Army General Hospital. The patient inclusion criteria were: (a) consecutive patients in Beijing Chaoyang Hospital and Bayi Brain Hospital from January 2009 to December 2016; (b) patients undergoing cerebral angiography via femoral catheterisation under local anaesthesia for the first time in life; and (c) patients aged 18–80 years. The exclusion criteria were: (a) unconscious patients; and (b) patients with severe heart disease (i.e. coronary heart disease, heart failure, or arrhythmia). VVR was defined as the presence of chest distress, dyspnoea, nausea and vomiting, and limb weakness and pallor, accompanied by a bradycardic episode (heart rate of < 60 beats/minute) and hypotension (systolic blood pressure < 100 mmHg) in the supine position, after other complications such as heart failure and myocardial infarction were excluded. Finally, 3107 patients were enrolled in this research, including 127 who developed VVR and 2980 in the non-VVR group.

Cerebral angiography procedures

All patients underwent preoperative solid and liquid fasting for over 8 hours. Lidocaine was administered at puncture points for local anaesthesia. Femoral artery puncture was performed using the Seldinger technique; subsequently, a size 5 French artery sheath was placed. Continuous intravenous infusion was carried out intraoperatively with 3000 IU heparin supplemented with 500 mL normal saline. The artery sheath was removed immediately after completion of the operation. Haemostasis by compression was implemented according to the triple-finger method, followed by pressure dressing with an elastic bandage or femoral artery compression device (Huangshi Diang Technology Co. Ltd., Huangshi, Hubei Province, China). The elastic bandage was removed 12 hours later, while the femoral artery compression device was removed 4–6 hours later. Blood pressure and electrocardiogram monitoring were carried out during the entire angiography procedure.

First aid at the time of VVR onset

Therapy for symptomatic bradycardia and hypotension was administered according to the attending physicians’ clinical judgement. Possible treatment measures included stopped or alleviated stimulation adjacent to femoral artery puncture points (e.g. stopped puncture or angiography, sheath removal, or alleviated oppression strength of femoral artery to facilitate haemostasis). Another measure was to maintain the patient’s supine position with the head turned to one side to avoid asphyxia. A third measure was immediate facilitation of oxygen inhalation and fluid infusion. A final measure was intravenous injection of atropine (1 mg) and dopamine (3–5 mg): if the heart rate remained unchanged, 200 mg dopamine was added into 250 mL normal saline for intravenous injection until the patient’s vital signs were stable.

Measurements

The baseline demographic and clinical variables were retrospectively identified via medical records. The demographic variables included age, sex and body mass index (BMI). Clinical variables included the medical conditions of hypertension, diabetes and hyperlipemia, actual solid and liquid fasting time, method of haemostasis by compression (elastic bandage or femoral artery compression device), time of VVR occurrence, time of VVR remission and VVR-induced complications.

Statistical analysis

All data processing and statistical analyses were performed using SPSS 22.0 (IBM Corp., Armonk, NY, USA). Statistical significance was defined as P < 0.05. Continuous variables (age, BMI and time of solid and liquid fasting) were presented as mean and standard deviation. One-sample Kolmogorov–Smirnov tests were used to identify normally distributed variables. Univariate logistic regression was performed to determine the association of VVR with other potential risk factors. Variables with a P value of less than 0.20 in the univariate logistic regression analysis were included in the multivariate logistic regression analysis.

Results

Demographic characteristics

In total, 3107 patients were enrolled in this study (Table 1), including 1628 male (52.40%) and 1479 female (47.60%) patients. Patient ages ranged from 18 to 80 years (mean 49.8 ± 11.84 years). The diseases for which the patients were admitted and treated were carotid artery or vertebral artery stenosis (n = 1782, 57.35%), intracranial aneurysm (n = 715, 23.01%), cerebral arteriovenous malformation (n = 209, 6.73%), dural arteriovenous fistula (n = 124, 4.00%), Moyamoya disease (n = 94, 3.03%), carotid cavernous fistula (n = 86, 2.77%) and others (n = 97, 3.12%). Of the patients included, 127 developed VVR (4.09%). The proportions of female patients in the VVR and non-VVR groups were 64.57% and 56.91%, respectively.

Table 1.

Univariate analysis for factors associated with VVR.

Variables	VVR group (n = 127)	Control group (n = 2980)	Total (n = 3107)	P value
Age (years)	51.34 ± 10.36	50.00 ± 11.37	49.8 ± 11.84	0.202
Gender
Female	82	1696	1778	0.088
Male	45	1284	1329
BMI (kg/m2)	26.41 ± 1.95	26.08 ± 1.87	26.10 ± 1.87	0.056
HBP
Yes	38	928	966	0.796
No	89	1945	2056
DM
Yes	4	89	93	0.916
No	123	2891	3014
HL
Yes	41	960	1000	0.981
No	86	2021	2107
Fasting time (hours)	12.24 ± 4.60	9.95 ± 3.17	10.04 ± 3.28	<0.001
Haemostasis method
EB	32	745	777	0.960
FACD	95	2235	2330

VVR: vasovagal reaction; HBP: high blood pressure; DM: diabetes mellitus; HL: hyperlipemia; EB: elastic bandage; FACD: femoral artery compression device.

Timing, treatment and prognosis of VVR

Of the 127 patients who experienced VVR, 106, eight, nine, three and one had VVR within 10 minutes after sheath removal, 10–120 minutes after sheath removal, at the time of puncture and sheath placement, during cerebral angiography and upon removal of the femoral artery compression device, respectively. Fluid infusion was applied after VVR in 22 cases; their blood pressure and heart rate returned to normal levels within several minutes to 2 hours, and clinical symptoms had disappeared. Atropine and/or dopamine were used for treatment in 105 cases; in 91, 11 and three, blood pressure and heart rate returned to normal levels within several minutes to 2 hours, within 6 hours (one case had supraventricular tachycardia and the sinus rhythm recovered 4 hours after symptomatic treatment), and within 24 hours (one case developed severe delirium accompanied by unconsciousness, which returned to normal 12 hours after treatment), respectively. None of the cases ultimately had a severe adverse reaction. The three patients who had VVR during catheter placement (manifested as decreased blood pressure and heart rate) gradually returned to normal levels after the procedure was stopped, while blood pressure dropped again after catheter placement. It was speculated that the VVR was induced by distraction stimulation at the arterial sheath site; thus, the cerebral angiography had to be stopped.

Comparison of potential influencing factors between VVR and non-VVR groups

Differences in age, BMI, sex ratios, the proportion of patients with hypertension, diabetes, and hyperlipemia and adoption of femoral artery compression device between the two groups were not statistically significant (P > 0.05). Compared with the control group, the VVR group had a significantly longer preoperative fasting time (P < 0.05) (Table 1).

Results of multivariate logistic regression analysis

Preoperative fasting time, BMI and the proportion of female patients were entered into the multivariate logistic regression model. The results indicated that preoperative fasting time was the only VVR risk factor associated with cerebral angiography (P < 0.001), with an odds ratio of 1.143 and 95% confidence interval of 1.102–1.185 (Table 2).

Table 2.

Multivariate logistic regression analysis for factors associated with VVR.

Variables	P value	OR (95% CI)
Gender	0.052
Female		Reference
Male		0.689 (0.473 ∼ 1.003)
BMI (kg/m2)	0.062	1.146 (0.993 ∼ 1.323)
Fasting time (hours)	<0.001	1.143 (1.102 ∼ 1.185)

VVR: vasovagal reaction; OR: odds ratio; CI: confidence interval; BMI: body mass index.

Discussion

VVR is a rare complication of cerebral angiography that is commonly seen during or within 30 minutes after femoral sheath removal.¹⁰ The association between the clinical characteristics of the 127 patients with VVR and cerebral angiography are summarised in this study, along with the timing and features of VVR. We found that VVR can occur not only at the time of sheath removal and shortly after that (when the patients had cerebral angiography via femoral catheterisation), but also at the time of sheath placement, during cerebral angiography and after removal of the femoral artery compression device. The associations between related risk factors of VVR and cerebral angiography were analysed in this paper; the results suggest that long preoperative fasting time is the most important risk factor for VVR associated with cerebral angiography.

Mechanism of VVR

The vagus nerve is extensively distributed in the vascular endothelial system. In the case of neuroregulation dysfunction, stimuli such as pain, distraction and oppression act on the cortical centre and hypothalamus, which induce abnormal excitation of the vagus nerve, leading to vasodilation and contraction dysfunction.¹ Significant small vessel dilation results in blood retention, decreased effective circulating blood volume and reduced blood pressure, leading to shock-like manifestations. This further affects cardiac and cerebral blood flow and may result in symptoms such as syncope in severe cases. Patients who receive vascular interventional examination and therapy are likely to develop VVR, which is commonly seen during or after sheath removal and haemostasis by compression.⁴ The following are the primary factors that affect VVR at the time of sheath removal and haemostasis by compression: first, excessive preoperative solid and liquid fasting time, insufficient fluid infusion can lead to metabolic disorders and increased secretion of related hormones. This gives rise to vascular smooth muscle contraction and renders it more sensitive to external stimulation. In particular, excessive solid and liquid fasting time and invasive surgery may result in haemodynamic disorders and induce collapse and shock. Second, inappropriate sheath removal methods, excessive oppression or compression strength, and poor intraoperative local anaesthesia increase patients’ pain sensitivity, leading to enhanced excitability and reflectivity of the vascular vagus nerve. Third, some patients are overstrung, which may lead to insomnia, enhanced sympathetic nerve excitability and reinforced myocardial contractility. This stimulates the pressure transducers in the left ventricle and carotid artery, causing enhanced vagus nerve excitability.⁴

The results of this study suggest that preoperative liquid and solid fasting time is the only significant risk factor. All patients in this study followed the medical advice of 8 hour preoperative solid and liquid fasting; however, such a time is extended or even greatly extended in clinical practice. Patients who receive selective cerebral angiography in the ward are directed to consume ‘no liquid or food after midnight on the day of surgery’ for convenient implementation of medical advice. The average fasting time in this research was 10.04 hours. More communication and cooperation between doctors and nurses regarding the management of solid and liquid fasting should be conducted in clinical practice to optimise the policy. The American Society of Anesthesiologists revised the traditional ‘npo after midnight’ policy in early 1999 and issued new suggestions for preoperative fasting: adult patients with no risk factor index of aspiration are allowed the consumption of clear liquids up to 2 hours before elective surgery, a light breakfast (tea and toast, for example) 6 hours before the procedure, and a heavier meal 8 hours beforehand.¹¹ However, the old fasting policy is dying hard for a variety of reasons.¹² The new fasting policy is still far from popular in China. This situation should be changed by continuous renewal of clinicians’ and anaesthetists’ thinking.

Strategies to prevent VVR

The mechanism of VVR is presently the subject of extensive study. The following measures are suggested to help prevent VVR: first, explanation of VVR-related knowledge to patients, excellent preoperative sleep, elimination of fear and tension psychology.¹ Second, sufficient local anaesthesia at the time of puncture and sheath placement could reduce pain stimulation.⁹ Third, an improved operating technique could reduce distraction stimulation on the artery.⁴ Fourth, a reasonable preoperative fasting time should be adopted, with excessive fasting time avoided.⁴ Fifth, blood volume should be expanded before and during cerebral angiography, and vasodilator use should be stopped when necessary. Finally, appropriate oppression strength is recommended after sheath removal.

Some scholars believe that preventive mediation before sheath removal is also effective. Rama et al. carried out a prospective, double-blinded, placebo controlled study and discovered that only 2.3% of the 88 cases receiving intravenous atropine injection before arterial sheath removal developed VVR (10.4% in the placebo group).¹ This suggests that intravenous atropine injection before extubation can prevent VVR during sheath removal and reduce corresponding processing costs. However, the incidence of VVR is not high and mostly has a good prognosis after timely and reasonable treatment.¹⁰ Moreover, intravenous atropine injection may lead to adverse reactions, such as dry mouth, arrhythmia and dysuresia. Therefore, this preventive measure has not been extensively adopted clinically.¹ In addition, applying lidocaine before sheath removal can reduce VVR, but such a method is not recommended by that paper’s authors.⁹ Routine use of local infiltration during sheath removal should be discouraged, as it leads to more pain and a higher frequency of VVR.⁹

Treatment and prognosis of patients with VVR

Most patients who develop VVR recover after timely, accurate treatment, and no severe clinical consequences occur.¹ However, interventional neuroradiologists might not understand this phenomenon; thus, we need to strengthen our understanding of it. Furthermore, attention should be paid to blood pressure and heart rate monitoring during the perioperative period. In particular, monitoring should be strengthened at the time of sheath removal and afterwards (especially within 30 minutes after sheath removal). Blood pressure, pulse, heart rate and subjective symptoms should be closely observed. The early discovery and treatment of VVR can prevent severe adverse outcomes.

Strengths and limitations

To the best of the authors’ knowledge, this is the first study to analyse the relationship between VVR risk factors and cerebral angiography via femoral catheterisation. However, the present study has some limitations. Although this was a multicentre study, bias may arise from the retrospective study design and limited number of cases. A prospective study with a larger sample size will be necessary to validate our findings.

Conclusion

When patients undergo cerebral angiography via femoral catheterisation, VVR can occur not only at the time of sheath removal and shortly afterwards, but also at the time of sheath placement, during cerebral angiography, and after removal of the femoral artery compression device. Excessive fasting time before cerebral angiography is an important risk factor for VVR associated with cerebral angiography. Clinicians should pay attention to this risk factor, optimise time management, and reduce unnecessary fasting time.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.