Ketamine: a possible medication for vasoplegia

Vasoplegia still presents a significant issue for doctors caring for cardiac surgery patients throughout the periprocedural period. Vasoplegia may occur up to 50% of the time, especially in patients with heart transplants and left ventricular assist device group. Although the exact etiology of vasoplegia is unknown, it is believed to be a result of dysregulation of the enzymes nitric oxide synthase and cyclic guanylate cyclase, as well as increased amounts of interleukins and other inflammatory chemicals.

Patients having cardiac surgery have had their levels of IL-6 tracked, and it has been shown that they considerably rise in the period after cross-clamp removal. Additionally, IL-6 has a vasodilator effect, which may help explain why systemic vascular resistance often decreases following cross-clamp removal. It seems sense that, especially in people who overexpress it, reducing or blocking IL-6 would help to reduce the hypotension seen following cross-clamp removal. An IL-6 receptor antibody called tocilizumab is gaining more attention as a therapy for COVID-19 individuals who have hyperimmune reactions to coronavirus infections. More significantly, tocilizumab typically alleviates hypotension within hours when taken to treat cytokine release syndrome. It is difficult to compare the IL-6-inhibiting effects of ketamine and tocilizumab since the mechanisms of the blockage differ: ketamine lowers IL-6 levels whereas tocilizumab competes with IL-6 receptors (increasing IL-6 levels, but preventing binding). A recently released paper examined the possibility of using ketamine as a vasoplegia preventative.

It is well known that the powerful analgesic and amnestic ketamine has IL-6-inhibitory effects. Ketamine's anti-inflammatory and sympathomimetic qualities may contribute to lowering the risk of vasoplegia in high-risk cardiac procedures such transplanting a left ventricular assist device (LVAD). The greatest evidence for the effectiveness of ketamine's IL-6 suppression in cardiac surgery comes from a meta-analysis from 2012, which found that ketamine seems to reduce IL-6 levels to one-third those of patients not receiving ketamine. Esketamine has about double the potency of racemic ketamine, so 4 to 8 mg/kg/h would be the same dosage in that case, which would probably have a big impact on the extubation duration. It is unknown at this time what ketamine dosage is required to reduce IL-6 levels in heart surgery patients. The idea that ketamine may be used as a tool to potentially avoid vasoplegia is a miniature version of the idea that anesthetics might serve purposes beyond simple sedation and analgesia. Ketamine may be used as a powerful antidepressant, as a therapy for status epilepticus that won't respond to other medications, and methylnaltrexone may lengthen cancer patients' lives, among other alternative applications for pharmacologic substances used in anesthesia. Hopefully, in the future, vasoplegia may be treated as a prophylactic measure using ketamine or other substances that modify inflammation in cardiac surgical care.

Reference –

Ortoleva JP. Ketamine, interleukin-6, and vasoplegia: Is prevention the best medicine?. Ann Card Anaesth 2023;26:114-6