Outcomes in cardiac surgery in 500 consecutive Jehovah's Witness patients: 21 year experience.

BACKGROUND: Refusal of heterogenic blood products can be for religious reasons as in Jehovah's Witnesses or otherwise or as requested by an increasing number of patients. Furthermore blood reserves are under continuous demand with increasing costs. Therefore, transfusion avoidance strategies are desirable. We describe a historic comparison and current results of blood saving protocols in Jehovah's Witnesses patients. METHODS: Data on 250 Jehovah's Witness patients operated upon between 1991 and 2003 (group A) were reviewed and compared with a second population of 250 patients treated from 2003 to 2012 (group B). RESULTS: In group A, mean age was 51 years of age compared to 68 years in group B. An iterative procedure was performed in 13% of patients in group B. Thirty days mortality was 3% in group A and 1% in group B despite greater operative risk factors, with more redo, and lower ejection fraction in group B. Several factors contributed to the low morbidity-mortality in group B, namely: preoperative erythropoietin to attain a minimal hemoglobin value of 14 g/dl, warm blood cardioplegia, the implementation of the Cornell University protocol and fast track extubation. CONCLUSIONS: Cardiac surgery without transfusion in high-risk patients such as Jehovah Witnesses can be carried out with results equivalent to those of low risk patients. Recent advances in surgical techniques and blood conservation protocols are main contributing factors.

A physiological model to evaluate drug kinetics in patients with hemorrhagic shock followed by fluid resuscitation. Application to amoxicillin-clavulanate.

PURPOSE: To build a physiologically based pharmacokinetic model describing drug kinetics in interstitial fluid in case of hemorrhagic shock, and to propose a simple method to determine the subset of influential parameters that may be estimated with the data at hand. METHODS: The model, which accounts for alterations of regional blood flows and body water distribution, was fitted to amoxicillin and clavulanate kinetic data, assessed in 12 trauma patients with hemorrhagic shock by comparison with 12 healthy volunteers. The predictions were the free concentrations of amoxicillin and clavulanate in 14 organs. RESULTS: In all tissues of trauma patients, the rate of distribution was lower, but the steady-state level was higher than those in healthy participants. Blood volume was reduced by 25% and blood flow in organs other than lung, brain, and heart were reduced by 18%. Compared with healthy subjects, the time that free amoxicillin concentration remained above 8 mg/L in the interstitial fluid of trauma patients was higher in blood and muscles, and lower in the tendon compartment. CONCLUSIONS: The results and predictions were consistent with the knowledge in this field. The model may be useful to optimize clinical trial designs and drug dosing regimens.

Physiological modeling for indirect evaluation of drug tissular pharmacokinetics under non-steady-state conditions: an example of antimicrobial prophylaxis during liver surgery.

Cefazolin, a time-dependent first-generation cephalosporin with non-linear binding to albumin, is widely recommended for antimicrobial prophylaxis during liver surgery to decrease the incidence of postoperative wound infections. The recommended protocol (2 g IV at anesthesia induction followed by 1 g 4 h later) is expected to maintain the free cefazolin concentration in exposed intratissular fluids above its minimal inhibitory concentration (MIC) for potentially encountered microorganisms, from skin incision to skin closure. Since this dosing protocol fails to take into account either of patients status (total body weight and renal function) or of surgical and anesthetic consequences (variations of cardiac output and regional blood flows, progressive decrease of plasma albumin concentration) on cefazolin tissular pharmacokinetics, a physiological modeling study was conducted to investigate protocol suitability for liver surgery in six populations: obese (body mass index >34), renal insufficiency (GFR = 10, 30 or 50 ml min(-1)) and high intraoperative blood loss (three times that usually observed during this surgery) and none of these features referred to as controls. A previously validated physiologically based pharmacokinetic (PB-PK) model for cefazolin in humans was used and then further adapted to simulate obese or renal insufficiency patients as well as the consequences of general anesthesia and liver surgery on cefazolin pharmacokinetics. Clinical data required for simulation (intraoperative kinetics of percent expired isoflurane and plasma albumin concentration, mean intraoperative blood loss) were obtained from 10 patients who underwent right hepatectomy in our institution. Using a fixed MIC of 2 microg ml(-1) against potentially encountered bacteria, it was concluded that the recommended dosing schedule was suitable in all tested populations, including obese patients, although prolongation of the interval between injections appeared advisable for renal insufficiency patients. Furthermore, when a MIC of 3 microg ml(-1) was considered, the recommended cefazolin-dosing regimen failed to maintain sufficient free cefazolin concentrations in the interstitial fluids during surgery in all tested populations except renal insufficiency patients (GFR < 50 ml min(-1)).

A comparison of two depths of prolonged neuromuscular blockade induced by cisatracurium in mechanically ventilated critically ill patients.

OBJECTIVES: To compare two levels of continuous cisatracurium-induced curarization in hypoxemic, ventilated patients. DESIGN AND SETTING: An open-labeled, multicenter, prospective, randomized study. PATIENTS: Hundred two patients with a ratio between arterial oxygen tension and inspired oxygen tension (PaO(2)/FIO(2)) less than 200 despite optimization of sedation and ventilation were randomized into group 1 (n=52) with an end point of no response at orbicularis oculi to train-of-four (TOF) stimulation or group 2 (n=50) with an end point of two responses. MEASUREMENTS AND RESULTS: The PaO(2)/FIO(2) and end-inspiratory plateau airway pressure (Pplat) were evaluated at baseline (before curarization) and at regular intervals once TOF end points had been attained for up to 2 h afterwards (T2 h). A decrease of 1 cmH(2)O or more of Pplat at T2 h compared to baseline was observed in 37% and 50% of the patients in groups 1 and 2, respectively (p=0.17). Time courses of PaO(2)/FIO(2) (mmHg) and Pplat (cmH(2)O) [mean (SD)] were equivalent in both groups, with a mild increase in PaO(2)/FIO(2) [p=0.0014; from 126 (33) to 141 (55) and from 134 (40) to 152 (52), respectively, in groups 1 and 2] and decrease in Pplat [p=0.016; from 29.1 (8.9) to 28.5 (8.8) and from 27.7 (7.5) to 26.6 (7.6)]. Median total durations of curarization were 28.9 h (3.1-219.7) in group 1 and 31.4 h (1.6-650.6) in group 2. Median cisatracurium infusion rates were 5.2 microg kg(-1) min(-1) (2.1-13.7) in group 1 and 3.6 microg kg(1) min(-1) (1.0-13.5) in group 2. The median delay to recovery from paralysis was shorter in group 2 (0.75 h vs 1.25 h; p=0.0008). CONCLUSION: When a prolonged curarization is decided upon in an ICU patient, a blockade at 2/4 at TOF at orbicularis oculi has similar effects on respiratory parameters as a blockade at 0/4, allowing a decrease in total administered doses and a shortening of the recovery of muscle strength after cessation of infusion.