**9. View to the future**

anesthetic infiltration or block of the nerve(s) which convey afferent stimuli leading to the reflex. Shende et al. studied the efficacy of peribulbar block with bupivacaine in patients operated for retinal detachment [79]. They collected 60 patients who were randomly assigned to receive either bupivacaine or IV morphine and studied the incidence and severity of the OCR. Apart from significantly reducing the incidence of OCR (30% vs 70%), peribulbar bupivacaine also attenuated the severity of the reflex [79]. Gupta et al. studied the effect of peribulbar block in comparison to topical application of local anesthetic in children scheduled for strabismus surgery. They found out that the incidence and severity of OCR intraoperatively was significantly reduced in children who received a peribulbar block [80]. Misurya et al. studied the effectiveness of prophylactic intravenous atropine sulphate which blocks the peripheral muscarinic receptors at the heart and retrobulbar xylocaine hydrochloride, which blocks the conduction at ciliary ganglion on the afferent limb of OCR. In this study, both atropine and retrobulbar xylocaine reduced the rate of OCR to 10–20%. But, when both

102 Abnormal Heart Rhythms

methods were used together, they were able to completely suppress the OCR [81].

If there is no contraindication to intravenous anticholinergics, atropine and/or glycopyrrolate IV may be used to partially prevent a TCR [82]. Hunsley et al. evaluated the efficacy of IV atropine and glycopyrrolate in the prevention of the OCR in children operated for strabismus. They tested different doses of the two drugs, glycopyrrolate 5 and 7.5 mg/kg and atropine 10 and 15 mg/kg. Overall, there is a reduction in the rate of bradycardia by 23.8–33.3% [83]. But these authors noticed that even higher doses of the two drugs, atropine 15mg/kg and glyco‐ pyrrolate 7.5mg/kg i.v., given 5 min before induction of anesthesia, are not sufficient to protect completely against the OCR in children. In a study done to evaluate the efficacy of IV or IM vagolytic agents (atropine and glycopyrrpolate) in children undergoing squint surgery, Mirakhur et al. evaluated them in a controlled study and found out that the administration of the anticholinergic agents in both the IV and the IM forms may decrease the occurrence of the OCR [84]. The overall frequency was approximately 40% (62 of 160 patients), but was 90% in those patients who did not receive anticholinergic drugs [84]. The authors concluded that the administration of anticholinergic drugs, even by the IM route, decreased the frequency, and glycopyrrolate 10 mg per kg being the most efficacious by this route [84]. As consequences of this literature and our own experience, the administration of anticholinergics has shown to be ineffective in completely preventing the TCR [73, 88]. The use of atropine is, nowadays, therefore questioned because cholinergic blockage reduces but does not totally prevent either bradycardia or hypotension in animals [85]. Another reason is that a trigeminal depressor response includes both the activation of vagal cardioinhibitory fibres and the inhibition of adrenergic vasoconstriction as demonstrated after electrical stimulation of the spinal trigemi‐ nal tract and trigeminal nuclear complex. In addition, atropine may cause serious cardiac arrhythmias itself, especially when halothane is the primary anaesthetic agent and hence the dose must be carefully chosen [86]. Prabhakar et al., for example, reported a 48-year-old female who developed severe bradycardia and hypotension during craniotomy for parietal convexity meningioma; she was unresponsive to atropine and successfully managed with epinephrine [89]. The action of adrenaline is to increase peripheral resistance via alpha-1 adrenoceptor vasoconstriction, so that blood is shunted to the body core, and the alpha-1 adrenoceptor response which is to increase cardiac rate and output [89]. This important case report under‐

The research on the TCR is now on a crossroad [39]. We have had a relative long phase in which case report and small case series have given substantial input to the development of the research on this topic. This research method has led to several biases in the TCR research: first in the prevalence and second in the risk factor, to mention only those both with that are mostly affected. This will be still needed in the future, of course, but we should now think to other research methods that lead to better evidence. In the first phase of TCR research, there were a lot of opinions that have led now to several really good systematic reviews that have created facts or at least trends. But starting from this newly created knowledge, there were now published several thinking models of the TCR to overcome on the one hand the complexity of information that is now available on this topic by generalizing and to make accurate forecast of risk for a specific operation. Such models helps us to better organize the information that is available and therefore make better decisions for our patients and adopt more effective treatment strategies. This new phase of TCR research has once again revolutionized the

**Figure 2.** Treatment recommendation for trigeminocardiac reflex[35].

importance of the TCR: It is now possible to preoperatively have a really good risk stratification of the occurrence of the TCR.

These thinking model have certainly to be checked out and adapted when needed in the future [see for example 37], but we have now a good basis canalize and generalize our information and knowledge. This will lead that the TCR goes away from an interesting and important phenomenon to a real and important fact of the skull base surgery.

Following the increasing complexity of our today's hospitals, there is also the need to adapt the TCR prevalences to the new reality. It is and remains, without any doubt, important to uncover risk factors and to make root analysis of TCR occurrence. But in a next step, we have also to look on what is going well in the non-TCR cases and to uncover what makes the processes robust and resilient. This will be going up from a TCR-research I to a TCRresearch II.
