Effects of Anesthetic Agents on Blood Brain Barrier Integrity: A Systematic Review.

BACKGROUND: The blood brain barrier (BBB) is a highly selective permeable barrier that separates the blood and the central nervous system. Anesthesia is an integral part of surgery, and there is little known about the impact of anesthetics on the BBB. Therefore, it is imperative to explore reversible or modifiable variables such as anesthetic agents that influence BBB integrity. We aimed to synthesize the literature pertaining to the various effects of anesthetics on the BBB. METHODS: MEDLINE, Embase, and Cochrane were searched from inception up to September 2022. RESULTS: A total of 14 articles met inclusion into the review. The articles included nine randomized control studies (64.3%) and five quasi-experimental studies (35.7%). Twelve studies used volatile anesthetics, one study used fentanyl intravenously, and one study used pentobarbital or ketamine intraperitoneally. BBB structural deficits following the administration of an anesthetic agent included ultrastructural deficits, decreases in tight junctions, and decreases in BBB components. BBB functional deficits included permeability increases following exposure to volatile anesthetics. However, two studies found decreased permeability after fentanyl, pentobarbital, or ketamine exposure. Moreover, the impact of anesthetics on the BBB seems to be related to the duration of exposure. Notably, study findings also suggest that changes following anesthetic exposure demonstrate some reversibility over the short-term. CONCLUSION: Overall, our systematic review highlights interesting findings pertaining to the impact of anesthetic agents on BBB integrity in previously healthy models. These findings and mechanisms should inspire future work to aid practitioners and healthcare teams potentially better care for patients.

The Impact of Sex, Circadian Disruption, and the ClockΔ19/Δ19 Genotype on Alcohol Drinking in Mice.

Shift work is associated with increased alcohol drinking, more so in males than females, and is thought to be a coping mechanism for disrupted sleep cycles. However, little is presently known about the causal influence of circadian rhythm disruptions on sex differences in alcohol consumption. In this study, we disrupted circadian rhythms in female and male mice using both environmental (i.e., shifting diurnal cycles) and genetic (i.e., ClockΔ19/Δ19 mutation) manipulations, and measured changes in alcohol consumption and preference using a two-bottle choice paradigm. Alcohol consumption and preference, as well as food and water consumption, total caloric intake, and weight were assessed in adult female and male ClockΔ19/Δ19 mutant mice or wild-type (WT) litter-mates, housed under a 12-hour:12-hour light:dark (L:D) cycle or a shortened 10-hour:10-hour L:D cycle. Female WT mice (under both light cycles) increased their alcohol consumption and preference over time, a pattern not observed in male WT mice. Compared to WT mice, ClockΔ19/Δ19 mice displayed increased alcohol consumption and preference. Sex differences were not apparent in ClockΔ19/Δ19 mice, with or without shifting diurnal cycles. In conclusion, sex differences in alcohol consumption patterns are evident and increase with prolonged access to alcohol. Disrupting circadian rhythms by mutating the Clock gene greatly increases alcohol consumption and abolishes sex differences present in WT animals.

Perioperative Complications and Anesthesia Practices in Managing Patients With Quadriplegia Undergoing Surgery: A Systematic Review.

Quadriplegia is associated with a multitude of health complications affecting numerous organ systems. Complications during the perioperative periods are not uncommon in this patient population due to abnormal responses to surgical stressors. Such complications include autonomic dysreflexia, cardiac ischemia, and respiratory compromise. Currently, there is no clear consensus on the ideal technique for perioperative anesthesia management in this population. In addition, the relationship between the perioperative complications and anesthesia practices have not been explored in-depth. Therefore, we aimed to investigate perioperative complications in the context of anesthesia that are associated with patients with quadriplegia undergoing various surgical procedures. Our PRISMA compliant systematic review included 12 articles covering the literature from inception to January 12, 2021. The review showed complications being pulmonary, cerebral, but most importantly and commonly cardiac in nature, with many patients suffering hypertension, and many others hypotension. In addition, our review showed that autonomic dysreflexia is common and in majority of patients, it was managed successfully with good recovery. Based on our findings, the use of anesthesia, either general or spinal, can be considered. Future studies are needed to elucidate the exact mechanisms involved in perioperative complications and anesthetic management that are associated with patients with quadriplegia. This review will aid in developing general recommendations based on the information available in the literature to guide perioperative management of this vulnerable patient population.

Reappearance of Neurological Deficits in Pathologic Brain: Are Sedatives and Opioids Culprits? A Systematic Review.

Following a brain insult, focal neurological deficits may develop. Despite resolution of these deficits with time, the subsequent administration of sedative medications and opioids may lead to recrudescence of previous neurological deficits. Therefore, the present systematic review aims to explore the role of different sedatives and opioid analgesics at reproducing focal neurological deficits in patients with previous brain insults undergoing surgery. Our PRISMA compliant systematic review covering the literature from 1990 to 2020 showed a consistent reoccurrence of neurological deficits following administration of benzodiazepines and opioids across 12 studies. It appears that in all studies, the manifestations were transient and affected mostly middle-aged patients (45 to 67 y of age). In addition, benzodiazepines and opioid antagonism by naloxone and flumazenil reverses the unmasking of prior neurological deficits. In contrast, it is not clear based on our study whether the unmasking or worsening of neurological deficits occurs following recent injuries or an older brain insult, although for most patients it appears to be the former. Future studies are needed to elucidate the mechanisms involved in unmasking prior deficits and/or extension of prior injuries by sedative and opioid analgesics. This review will aid in developing prospective studies on individual sedative medications and their effects on unmasking neurological deficits in patients with multiple brain pathologies.