A Non-Comparative Prospective Pilot Study of Ketamine for Sedation in Adult Septic Shock.

Abstract

Sedation and analgesia in the intensive care unit (ICU) for patients with sepsis can be challenging. Opioids and benzodiazepines can lower blood pressure and decrease respiratory drive. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that provides both amnesia and analgesia without depressing respiratory drive or blood pressure. The purpose of this pilot study was to assess the effect of ketamine on the vasopressor requirement in adult patients with septic shock requiring mechanical ventilation. We conducted a two-phase study in a multi-disciplinary adult ICU at a tertiary medical center. The first phase was a retrospective chart review of patients admitted with septic shock between July 2010 and July 2011; 29 patients were identified for a historical control group. The second phase was a prospective, non-randomized, open-label pilot study. Patients were eligible for inclusion if they were 18-89 yr of age with a diagnosis of septic shock, who also required mechanical ventilation for at least 24 h, concomitant sedation, and vasopressor therapy. Pregnant patients, patients in the peri-operative timeframe, and patients with acute coronary syndrome were excluded. Patients enrolled in the phase two pilot study received ketamine as the primary sedative. Ketamine was administered as a 1-2 mg/kg IV bolus, then as a continuous infusion starting at 5 mcg/kg/min, titrated 2 mcg/kg/min every 30 min as needed to obtain a Richmond Agitation Sedation Scale (RASS) goal of -1 to -2. If continuous sedation was still required after 48 h, patients were transitioned off ketamine and sedative strategy reverted to usual ICU sedation protocol. The primary outcome was the dose of vasopressor required at 24, 48, 72 and 96 h after enrollment. Secondary outcomes included cumulative ketamine dose, additional sedative and analgesics used, cumulative sedative and analgesic dosing at all time periods, corticosteroid use, days of mechanical ventilation, ICU LOS, hospital LOS, and mortality. Contiguous data were analyzed with unpaired t-tests and categorical data were analyzed with two-tailed, Fisher's exact test. This study was approved by our Institutional Review Board. From January 2012 to April 2015, a total of 17 patients were enrolled. Patient characteristics were similar in the control and study group. Ketamine was discontinued in one patient due to agitation at 36 h. There was a trend towards decreased norepinephrine and vasopressin use in the study group at all time periods. Regarding secondary outcomes, the study group received less additional analgesia with fentanyl at 24 and 48 h (p < 0.001), and less additional sedation with lorazepam, midazolam or dexmedetomidine at 24 h (p = 0.015). This pilot study demonstrated a trend towards decreased vasopressor dose, and decreased benzodiazepine and opiate use when ketamine is used as the sole sedative. The limitations to our study include a small sample size and those inherent in using a retrospective control group. Our findings should be further explored in a large, randomized prospective study.