**5. Risk factors for occurrence of the trigeminocardiac reflex**

to occur in up to 67% after ophthalmic surgery [24]. Because of publication bias, the real prevalence may be substantially smaller, even the peripheral TCR has generally a higher prevalence than the central TCR. According to the senior author Schaller's experience, the central TCR occurs in up to 10–18% of the patients [1, 25–27]. In a retrospective time-series review of 125 patients operated for tumours of the cerebello-pontine angle, Schaller et al. noticed the TCR occurrence in 11%. [4] Three of these patients in this series developed asystole which lasted from 30 to 70 seconds [1]. In contrast to earlier studies on OCR, Schaller – for the first time – took into consideration both the heart rate and blood pressure and defined TCR as

heart rate and mean arterial blood pressure (MABP) 20% lower than the baseline [1].

In another retrospective time-series study, Schaller also showed the TCR occurrence during microvascular decompression of the trigeminal nerve for trigeminal neuralgia [27]. In this review on 28 patients, the prevalence of TCR was up to 18% with the same definition used as in his prior above-mentioned study [27]. TCR was also reported during transsphenoidal surgery for pituitary adenoma [11, 26, 28]. Among 117 patients who underwent transsphe‐ noidal surgery for pituitary adenoma, 10% developed a TCR during the surgical procedure [26]. Peripheral stimulation of the nasopharynx may also lead to (peripheral) TCR [11].

In several other neurosurgical procedures, there exists only case reports or small case series,

The TCR is a clinical phenomenon that reflects interactions of many organs to the brain [4, 12, 14, 19, 29–31]. Among all the organs, the connection between heart and brain is unique and presents a wide array of clinical manifestations when the TCR gets incited [16]. These clinical signs include drop in heart rate and blood pressure, asytole, ventricular tachycardia/fibrilla‐ tion, ST-T wave changes and other forms of arrhythmias [4, 5, 12–16, 29, 31–65]. Stimulus especially in form of stretch has found to be the strongest inciting factor for the TCR [1]. However, mild stimulus may also results into TCR episodes [3, 18, 35]. Chowdhury et al. reported that mild stimulus in the form of skin closure could able to produce transient asystole and questioned about the severity of stimulus and TCR manifestation. In another report, Chowdhury et al. further suggested that various manifestations of TCR episodes (bradycardia, hypertension, asystole) as well as different subtypes of TCR (peripheral and central) could manifest in the same patient [4, 13]. Again, in this report, transient asystole manifested during the skin closure as well [4]. Author postulated that the different sympathetic outflow responses could be due to different depths of anaesthesia, which coupled with different forms of TCR stimulation probably contributed to different haemodynamic responses in the same patient and obscured the classical manifestation of TCR [3]. Strikingly, the cardiovascular changes of TCR phenomenon mainly reported due to acute stimulation (peri-operatively) of trigeminal nerve; however, Chowdhury and Schaller highlighted the first description of chronic form of

As highlighted in a review by Chowdhury et al., the other rare cardiac perturbation i.e. coronary spasm in neurosurgical patients may be the mere manifestation of TCR events [16].

so that a robust prevalence of TCR occurrence is not (yet) known.

**4. Heart and the trigeminocardiac reflex**

TCR [40].

98 Abnormal Heart Rhythms

Because of the still fragmented knowledge about the TCR and the consecutive limited therapeutic options, the risk factors gain increased importance. However, it is best known that such risk factors are not easy to proof in retrospective studies as they are predominantly available in TCR research. The risk factors already known to increase the incidence of TCR include (i) hypercapnia, (ii) hypoxemia, (iii) light general anaesthesia, (iv) age (more pro‐ nounced in children), (v) the nature of the provoking stimulus (stimulus strength and duration) and (vi) drugs. Recent systematic reviews, however, have identified several potential cofounders for these mentioned risk factors. Drugs known to increase the TCR include (i) potent narcotic agents (sufentanil and alfentanil) [66, 67], (ii) beta-blockers and (iii) calcium channel blockers [68]. Narcotics may augment vagal tone through their inhibitory action on the sympathetic nervous system [1, 69–71]. Beta-blockers reduce the sympathetic response of the heart and, by so doing, augment the vagal cardiac response resulting in bradycardia. Calcium channel blockers result in peripheral arterial smooth muscle relaxation and vasodilatation causing reduction in blood pressure. In patients undergoing trigeminal manipulations, this worsens the vagal effect that occurs in some patients. In previous publications about the TCR, the study design (mostly case control) may have led to different bias regarding the risk factors [39], such as recall bias and non-response bias to only mention two examples. From this point of view, a randomized controlled trial or a systematic review are requested to show best a cause-and-effect relationship for the risk factors.

In the recent years, it has more and more raised the question if the main search on risk factors is not a too linear thinking to overcome the complexity of the TCR. However, we think that risk factors are still an important key to better understand the TCR; even these risk factors have led to the development of the thinking model of TCR rather than to direct treatment conse‐ quences.
