Authors’ response
High doses of ketamine to improve neuronal edema in subarachnoid hemorrhage: preliminary clinical data do not suggest an adverse effect on renal function
Edgar Santos, Sebastian Major, Renán Sánchez-Porras, and Jens P. Dreier
Thank you for your kind interest in our work. Aneurysmal subarachnoid hemorrhage (aSAH) is indeed characterized by an impressive list of potential complications. Thus, aSAH is associated with ~ 20 relevant intracranial and > 30 extracranial complications [5]. On top of this, there are numerous side effects of a wide range of medications. For our retrospective cohort study, we identified 66 patients from a prospectively collected database using prespecified criteria (32 from the University of Heidelberg, recruited 2004–2014, and 34 from Charité–Universitätsmedizin Berlin, recruited 2005–2010) [1]. Laboratory values are readily available for the Berlin patients of whom 14 were treated with S-ketamine. The Acute Kidney Injury Network (AKIN) has defined AKI as abrupt (within 48 h) reduction in kidney function leading to an absolute increase in serum creatinine of ≥ 0.3 mg/dl, an increase in creatinine of ≥ 50%, or a reduction in urine output (< 0.5 ml/kg/h for > 6 h) [6]. For the requested exploratory analysis, we here consider creatinine during the first 45 days after the initial hemorrhage (in total, 417 values, 12 ± 9 tests per patient). Based on this, 4 of 34 patients (12%) developed AKI: 2 of 20 (10%) without S-ketamine, 1 of 5 (20%) with S-ketamine below, and 1 of 9 (11%) with S-ketamine > 2 mg/kg body weight (BW)/h. In the latter patient, high-dose S-ketamine and mannitol treatment started on day 8 when she developed a dilated left pupil, decorticate posturing, intracranial pressure (ICP) above 20 mmHg, and computed tomography-proven transtentorial herniation. Serum creatine increased from 0.4 to 0.9 mg/dl between days 8 and 10 with full recovery thereafter. In parallel, a urinary tract infection with Escherichia coli was found and treated with ceftriaxone. In addition, the patient also suffered from arterial hypertension and systemic lupus erythematodes so that at least 5 potential etiologies of kidney damage coincided. In the follow-up (day 194), she was fully oriented but showed hemiparesis and mild aphasia (extended Glasgow Outcome Scale: upper severe disability). In the 9 patients, S-ketamine > 2 mg/kg BW/h did not lead to significant creatinine changes overall (before S-ketamine, 0.65 ± 0.17 mg/dl; during high-dose S-ketamine, 0.68 ± 0.18 mg/dl; paired t test; P = 0.443). It should be taken into account that ketamine, in addition to its potentially beneficial effects on spreading depolarizations [7], also leads to reduction in ICP and to savings in catecholamines with potential kidney protection [8]. Nonetheless, although our data do not suggest that S-ketamine increases the risk for AKI, renal function should be closely monitored.