Reply to Sagliocco, O.; Betelli, M. Comment on "Fierro et al. Severe Hypotension, Bradycardia and Asystole after Sugammadex Administration in an Elderly Patient. Medicina 2021, 57, 79".

We thank Dr. Sagliocco and Dr. Betelli for their comments [...].

Severe Hypotension, Bradycardia and Asystole after Sugammadex Administration in an Elderly Patient.

Background and Objectives: Sugammadex is a modified γ-cyclodextrin largely used to prevent postoperative residual neuromuscular blockade induced by neuromuscular aminosteroid blocking agents. Although Sugammadex is considered more efficacious and safer than other drugs, such as Neostigmine, significant and serious complications after its administration, such as hypersensitivity, anaphylaxis and, more recently, severe cardiac events, are reported. Case presentation: In this report, we describe the case of an 80-year-old male with no medical history of cardiovascular disease who was scheduled for percutaneous nephrolithotripsy under general anesthesia. The intraoperative course was uneventful; however, the patient developed a rapid and severe hypotension, asystole and cardiac arrest after Sugammadex administration. Spontaneous cardiac activity and hemodynamic stability was restored with pharmacological therapy and chest compression. The patient was stabilized and discharged uneventfully on postoperative day 10. Conclusions: The potential causes of cardiac arrest after Sugammadex administration have been carefully considered, yet all indications point to Sugammadex as the direct causative agent. On the basis of laboratory and clinical tests, we can exclude among the cause of bradycardia, Kounis syndrome, acute myocardial infarction, coronary spasm and other arrhythmias, but not anaphylaxis. Although Sugammadex is considered an increasingly important option in the prevention of postoperative residual neuromuscular blockade, anesthesiologists should consider it a causative agent of cardiac arrest during surgery. This case highlights the necessity of increased pharmacovigilance and further studies to examine Sugammadex safety and mechanism through which it may cause severe bradycardia, hypotension and cardiac arrest.

Noninvasive respiratory support in the perioperative setting: a narrative review.

The application of preoperative noninvasive respiratory support (NRS) has been expanding with increasing recognition of its potential role in this setting as a physiological optimization for patients with a high risk of developing atelectasis and postoperative pulmonary complications (PPC). The increased availability of high-performance anesthesia ventilator machines providing an easy way for NRS support in patients with reduced lung function should not be under-evaluated. This support can reduce hypoxia, restore lung volumes and theoretically reduce atelectasis formation after general anesthesia. Therapeutic purposes should also be considered in the perioperative setting, such as preoperative NRS to optimize treatment of patients' pre-existing diseases, e.g., sleep-disordered breathing. Finally, the recent guidelines for airway management suggest preoperative NRS application before anesthesia induction in difficult airway management to prolong the time needed to secure the airway with an orotracheal tube. This narrative review aims to revise all these aspects and to provide some practical notes to maximize the efficacy of perioperative noninvasive respiratory support.

Radial artery cannulation and reversible skin pallor after saline flushing. What do you do?

Radial artery cannulation is widely used in intensive care units. However, it is not free from risks. We cannulated the left radial artery in a 75-year-old man and observed this phenomenon but found poor information from literature searches. We propose that the pallor around the insertion site after flushing the line with saline may be due to the cold and high-pressure injection, causing localized superficial vasospasm. Luckily, skin pallor resolved once the arterial lavage was stopped. This phenomenon may be less observed by practitioners leading to underestimating the possibility of related complications.

Effects of a Small-Molecule Perforin Inhibitor in a Mouse Model of CD8 T Cell-Mediated Neuroinflammation.

BACKGROUND AND OBJECTIVES: Alteration of the blood-brain barrier (BBB) at the interface between blood and CNS parenchyma is prominent in most neuroinflammatory diseases. In several neurologic diseases, including cerebral malaria and Susac syndrome, a CD8 T cell-mediated targeting of endothelial cells of the BBB (BBB-ECs) has been implicated in pathogenesis. METHODS: In this study, we used an experimental mouse model to evaluate the ability of a small-molecule perforin inhibitor to prevent neuroinflammation resulting from cytotoxic CD8 T cell-mediated damage of BBB-ECs. RESULTS: Using an in vitro coculture system, we first identified perforin as an essential molecule for killing of BBB-ECs by CD8 T cells. We then found that short-term pharmacologic inhibition of perforin commencing after disease onset restored motor function and inhibited the neuropathology. Perforin inhibition resulted in preserved BBB-EC viability, maintenance of the BBB, and reduced CD8 T-cell accumulation in the brain and retina. DISCUSSION: Therefore, perforin-dependent cytotoxicity plays a key role in the death of BBB-ECs inflicted by autoreactive CD8 T cells in a preclinical model and potentially represents a therapeutic target for CD8 T cell-mediated neuroinflammatory diseases, such as cerebral malaria and Susac syndrome.

Tissue-resident CD8+ T cells drive compartmentalized and chronic autoimmune damage against CNS neurons.

The mechanisms underlying the chronicity of autoimmune diseases of the central nervous system (CNS) are largely unknown. In particular, it is unclear whether tissue-resident memory T cells (TRM) contribute to lesion pathogenesis during chronic CNS autoimmunity. Here, we observed that a high frequency of brain-infiltrating CD8+ T cells exhibit a TRM-like phenotype in human autoimmune encephalitis. Using mouse models of neuronal autoimmunity and a combination of T single-cell transcriptomics, high-dimensional flow cytometry, and histopathology, we found that pathogenic CD8+ T cells behind the blood-brain barrier adopt a characteristic TRM differentiation program, and we revealed their phenotypic and functional heterogeneity. In the diseased CNS, autoreactive tissue-resident CD8+ T cells sustained focal neuroinflammation and progressive loss of neurons, independently of recirculating CD8+ T cells. Consistently, a large fraction of autoreactive tissue-resident CD8+ T cells exhibited proliferative potential as well as proinflammatory and cytotoxic properties. Persistence of tissue-resident CD8+ T cells in the CNS and their functional output, but not their initial differentiation, were crucially dependent on CD4+ T cells. Collectively, our results point to tissue-resident CD8+ T cells as essential drivers of chronic CNS autoimmunity and suggest that therapies targeting this compartmentalized autoreactive T cell subset might be effective for treating CNS autoimmune diseases.