Cerebral Near-Infrared Spectroscopy in Adult Patients Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Acute cerebral complications (ACC) of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are associated with poor long-term neurologic outcome. We described the role of rSO2 monitoring in detecting ACC and desaturations and their relationship with poor outcome when employing VA-ECMO. METHODS: Retrospective analysis of patients monitored by cerebral frontal near-infrared spectroscopy (NIRS) (CAS Medical Systems Inc., Branford, CT, USA) during VA-ECMO (November 2008-December 2015). ACC was defined as the presence of stroke and/or brain death, while cerebral desaturation as cortical oxygen tissue saturation (rSO2) < 60%. RESULTS: Fifty-six of 159 VA-ECMO patients (age 55 [36-60] years) were included; 18 (32%) developed ACC and 36 died (64%). Cerebral desaturation occurred in 43 (74%) patients, who had a higher mortality than those without cerebral desaturation (74 vs. 31%). A high sequential organ failure assessment (SOFA) score on the first day of ECMO (OR 1.40 [95% CIs 1.06-1.84]) and the minimum ECMO blood flow during the first 4 days of therapy (OR 3.05 [1.01-9.17]) were independently associated with the occurrence of cerebral desaturation. Cerebral desaturation occurred more frequently in patients with ACC than others (94 vs. 68%); patients with ACC also had a lower minimal rSO2 over time (49 vs. 54%) and more frequently had high right-left rSO2 differences (33 vs. 8%), which were both independent predictors of ACC. The occurrence of cerebral desaturation (OR 7.93 [1.62-38.74]) and high lactate concentrations during the first 4 days of ECMO support (OR 1.22 [1.03-1.46]) was independently associated with hospital mortality. CONCLUSIONS: Monitoring of rSO2 could be considered as an interesting tool to monitor the brain of patients on VA-ECMO.

New Regimen for Continuous Infusion of Vancomycin in Critically Ill Patients.

Despite the development of new agents with activity against Gram-positive bacteria, vancomycin remains one of the primary antibiotics for critically ill septic patients. Because sepsis can alter antimicrobial pharmacokinetics, the development of an appropriate dosing strategy to provide adequate concentrations is crucial. The aim of this study was to prospectively validate a new dosing regimen of vancomycin given by continuous infusion (CI) to septic patients. We included all adult septic patients admitted to a mixed intensive care unit (ICU) between January 2012 and May 2013, who were treated with a new vancomycin CI regimen consisting of a loading dose of 35 mg/kg of body weight given as a 4-h infusion, followed by a daily CI dose adapted to creatinine clearance (CrCL), as estimated by the Cockcroft-Gault formula (median dose, 2,112 [1,500 to 2,838] mg). Vancomycin concentrations were measured at the end of the loading dose (T1), at 12 h (T2), at 24 h (T3), and the day after the start of therapy (T4). Vancomycin concentrations of 20 to 30 mg/liter at T2, T3, and T4 were considered adequate. A total of 107 patients (72% male) were included. Median age, weight, and CrCL were 59 (interquartile range [IQR], 48 to 71) years, 75 (IQR, 65 to 85) kg, and 94 (IQR, 56 to 140) ml/min, respectively. Vancomycin concentrations were 44 (IQR, 37 to 49), 25 (IQR, 21 to 32), 22 (IQR, 19 to 28), and 26 (IQR, 22 to 29) mg/liter at T1, T2, T3, and T4, respectively. Concentrations were adequate in 56% (60/107) of patients at T2, in 54% (57/105) at T3, and in 73% (41/56) at T4. This vancomycin regimen permitted rapid attainment of target concentrations in serum for most patients. Concentrations were insufficient in only 16% of patients at 12 h of treatment.

Vancomycin population pharmacokinetics during extracorporeal membrane oxygenation therapy: a matched cohort study.

INTRODUCTION: The aim of this study was to describe the population pharmacokinetics of vancomycin in critically ill patients treated with and without extracorporeal membrane oxygenation (ECMO). METHODS: We retrospectively reviewed data from critically ill patients treated with ECMO and matched controls who received a continuous infusion of vancomycin (35 mg/kg loading dose over 4 hours followed by a daily infusion adapted to creatinine clearance, CrCl)). The pharmacokinetics of vancomycin were described using non-linear mixed effects modeling. RESULTS: We compared 11 patients treated with ECMO with 11 well-matched controls. Drug dosing was similar between groups. The median interquartile range (IQR) vancomycin concentrations in ECMO and non-ECMO patients were 51 (28 to 71) versus 45 (37 to 71) mg/L at 4 hours; 23 (16 to 38) versus 29 (21 to 35) mg/L at 12 hours; 20 (12 to 36) versus 23 (17-28) mg/L at 24 hours (ANOVA, P = 0.53). Median (ranges) volume of distribution (Vd) was 99.3 (49.1 to 212.3) and 92.3 (22.4 to 149.4) L in ECMO and non-ECMO patients, respectively, and clearance 2.4 (1.7 to 4.9) versus 2.3 (1.8 to 3.6) L/h (not significant). Insufficient drug concentrations (that is drug levels < 20 mg/dL) were more common in the ECMO group. The pharmacokinetic model (non-linear mixed effects modeling) was prospectively validated in five additional ECMO-treated patients over a 6-month period. Linear regression analysis comparing the observed concentrations and those predicted using the model showed good correlation (r(2) of 0.67; P < 0.001). CONCLUSIONS: Vancomycin concentrations were similar between ECMO and non-ECMO patients in the early phase of therapy. ECMO treatment was not associated with significant changes in Vd and drug clearance compared with the control patients.

Ultrasound Guided Continuous Sciatic Nerve Block for Acute Herpetic Neuralgia.

Herpes Zoster (HZ) is the reactivation of a well-known viral disease which manifests itself with painful skin lesions. An effective analgesic method during the acute phase of HZ can contribute to decrease the incidence of postherpetic neuralgia (PHN) by reducing neural sensitization. Sciatic nerve block (SNB) is useful in the management of distal lower extremity pain sustained by the sciatic nerve. We describe our experience with a continuous ultrasound guided subgluteus sciatic nerve block in a patient with herpetic neuralgia- (HN-) related refractory acute left leg pain.

ß-Lactam pharmacokinetics during extracorporeal membrane oxygenation therapy: A case-control study.

Most adult patients receiving extracorporeal membrane oxygenation (ECMO) require antibiotic therapy, however the pharmacokinetics of ß-lactams have not been well studied in these conditions. In this study, data from all patients receiving ECMO support and meropenem (MEM) or piperacillin/tazobactam (TZP) were reviewed. Drug concentrations were measured 2h after the start of a 30-min infusion and just before the subsequent dose. Therapeutic drug monitoring (TDM) results in ECMO patients were matched with those in non-ECMO patients for (i) drug regimen, (ii) renal function, (iii) total body weight, (iv) severity of organ dysfunction and (v) age. Drug concentrations were considered adequate if they remained 4-8× the clinical MIC breakpoint for Pseudomonas aeruginosa for 50% (TZP) or 40% (MEM) of the dosing interval. A total of 41 TDM results (27 MEM; 14 TZP) were obtained in 26 ECMO patients, with 41 matched controls. There were no significant differences in serum concentrations or pharmacokinetic parameters between ECMO and non-ECMO patients, including Vd [0.38 (0.27-0.68) vs. 0.46 (0.33-0.79)L/kg; P=0.37], half-life [2.6 (1.8-4.4) vs. 2.9 (1.7-3.7)h; P=0.96] and clearance [132 (66-200) vs. 141 (93-197)mL/min; P=0.52]. The proportion of insufficient (13/41 vs. 12/41), adequate (15/41 vs. 19/41) and excessive (13/41 vs. 10/41) drug concentrations was similar in ECMO and non-ECMO patients. Achievement of target concentrations of these ß-lactams was poor in ECMO and non-ECMO patients. The influence of ECMO on MEM and TZP pharmacokinetics does not appear to be significant.

Strongyloides disseminated infection successfully treated with parenteral ivermectin: case report with drug concentration measurements and review of the literature.

We report the case of an immunosuppressed patient with Strongyloides disseminated infection who was successfully treated with the veterinary parenteral form of ivermectin. A kidney transplant recipient developed disseminated infection with Strongyloides stercoralis. Because oral treatment with ivermectin was not possible, subcutaneous ivermectin (75 µg/kg/day, then 200 µg/kg/day) was given for 9 days, with clinical improvement and disappearance of all larvae. Serum ivermectin concentrations were between 15.6 ng/mL and 19.7 ng/mL during the 9 days of therapy; however, drug accumulation (plasma levels >40 ng/mL) 48 h after discontinuation of therapy was associated with the development with encephalopathy. We also review all cases of human disseminated Strongyloides infection treated with parenteral ivermectin.