Ceftazidime Plasma Concentrations and Neurotoxicity: The Importance of Therapeutic Drug Monitoring in Patients Undergoing Different Modalities of Renal Replacement Therapy. A Grand Round.

ABSTRACT: Ceftazidime-avibactam (CTZ-AVM) is a novel cephalosporin/beta-lactamase inhibitor with broad-spectrum activity against multidrug-resistant Pseudomonas aeruginosa . Ceftazidime-induced neurotoxicity is a well-described adverse effect, particularly in patients with renal insufficiency. However, appropriate dosing of ceftazidime-avibactam in patients undergoing renal replacement therapy (RRT) is sparsely investigated, and therapeutic drug monitoring to guide dosing remains lacking. Furthermore, when dose adjustment for impaired renal function is based on CTZ-AVM product information, inferior cure rates have been obtained compared with those with the standard therapy for intra-abdominal infections. Maintaining an effective dose while avoiding toxicity in these patients is challenging. Here, the authors describe the case of a critically ill patient, undergoing 2 modalities of RRT, who developed ceftazidime-induced neurotoxicity as confirmed using ceftazidime therapeutic drug monitoring. This case illustrates a therapeutic drug monitoring-based approach for guiding ceftazidime-avibactam dosing in this context and in diagnosing the cause of neurological symptoms and signs.

Assessment of Common Preoxygenation Strategies Outside of the Operating Room Environment.

OBJECTIVES: Preoxygenation prior to intubation aims to increase the duration of safe apnea by causing denitrogenation of the functional residual capacity, replacing this volume with a reservoir of oxygen. In the operating room (OR) the criterion standard for preoxygenation is an anesthetic circuit and well-fitting face mask, which provide a high fractional inspired oxygen concentration (FiO2 ). Outside of the OR, various strategies exist to provide preoxygenation. The objective was to evaluate the effectiveness of commonly used preoxygenation strategies outside of the OR environment. METHODS: This was a prospective randomized unblinded study of 30 healthy staff volunteers from a major trauma center emergency department (ED) in Sydney, Australia. The main outcome measure is fractional expired oxygen concentration (FeO2 ) measured after a 3-minute period of tidal volume breathing with seven different preoxygenation strategies. RESULTS: The mean FeO2 achieved with the anesthetic circuit was 81.0% (95% confidence interval [CI] = 78.3% to 83.6%), bag-valve-mask (BVM) 80.1% (95% CI = 76.5% to 83.6%), BVM with nasal cannula (NC) 74.8% (95% CI = 72.0% to 77.6%), BVM with positive end-expiratory pressure valve (PEEP) 78.9% (95% CI = 75.4% to 82.3%), BVM + NC + PEEP 75.5% (95% CI = 72.2% to 78.9%), nonrebreather mask (NRM) 51.6% (95% CI = 48.8% to 54.4%), and NRM + NC 57.1% (95% CI = 52.9% to 61.2%). Preoxygenation efficacy with BVM strategies was significantly greater than NRM strategies (p < 0.01) and noninferior to the anesthetic circuit. CONCLUSIONS: In healthy volunteers, the effectiveness of BVM preoxygenation was comparable to the anesthetic circuit (criterion standard) and superior to preoxygenation with NRM. The addition of NC oxygen, PEEP, or both did not improve the efficacy of the BVM device.