High doses of ketamine to improve neuronal edema in subarachnoid hemorrhage: we should consider other undesirable organ targets

Excerpt

We read with interest the recent article by Santos et al. regarding the use of S-ketamine to decrease spreading depolarizations and improve cytotoxic neuronal edema in patients with aneurysmal subarachnoid hemorrhage [1]. They note that the active enantiomer S(+) ketamine is two times stronger than the racemic form and four times stronger than the R(−) enantiomer [1]. Further, they report that the upper therapeutically recommended dose of S-ketamine for sedation is 2 mg/kg BW/h, but if deemed necessary, neuro-intensivists are using doses of up to 7 mg/kg BW/h. We would like to make some comments. S-ketamine is a non-competitive N-methyl-d-aspartate (NMDA) receptor ion channel blocker [2]. Its action is not limited to the brain, and as intensivists, we need to be mindful of the effects of ketamine upon other organs, especially when ketamine is used in high doses. Negative effects of these high doses have been described in the kidney [2, 3]. Renal medullary oxygenation is strictly balanced by a series of control mechanisms, which match regional oxygen supply and consumption [2]. Failure of these controls renders the outer medullary region susceptible to acute or repeated episodes of hypoxic injury, which may lead to acute tubular necrosis (ATN), especially of the thick ascending limbs [2]. In the kidney, any increase in circulating catecholamines (especial1y epinephrine) will cause vasoconstriction via the alpha-receptors and activation of the renin-angiotensin system [2]. As a result, despite normal renal blood flow, intramedullary ischemia may occur [2]. Increases in sympathomimetic hormones lead to renal cortical vasoconstriction, which is a compensatory attempt by the body to redistribute blood flow to the renal medulla, but in fact, it causes ischemia [2, 4]. S(+)-ketamine is about three to four times more potent as an anesthetic than R(−)-ketamine, but an equipotent dose of S(+)-ketamine alone may show weaker norepinephrine and serotonin uptake inhibition than R(−)-ketamine at anesthetic effective doses [2]. In a rat model of ischemia reperfusion of the kidney, high doses of S(+)-ketamine induced a higher score of histological changes, with the rise in catecholamine blood concentration thought to be the likely cause [2]. Further studies are needed to investigate the relationship between high doses of ketamine and the risk of acute kidney injury (AKI). In the study of Santos et al., it would be interesting to know the data regarding the rate of AKI between the control group and the high-dose group. …