Clinical Outcome in Patients with Nosocomial COVID-19 Infection After Thoracic Surgery.

In the present study, we retrospectively evaluated outcomes in 8 patients (mean age 67 ± 7, range 55-77 years; male/female 7/1) who acquired nosocomial COVID-19 infection postoperatively out of the 39 adults who underwent elective thoracic surgery in November 2020. All patients were tested negative for COVID-19 on admission. The mortality rate in the eight patients was 25%. The surviving six patients were discharged in a good clinical condition. Fatal outcomes were due to the development of severe and unrelenting acute respiratory distress syndrome (ARDS) and were associated with preoperatively reduced serum albumin (<3 g/dL), an open surgical approach, oxygen saturation <90% at the time of COVID-19 diagnosis, and the real-time PCR cycle threshold (Ct) value <20. A high mortality rate indicates a need for systematic and frequent COVID-19 screening in patients scheduled for elective thoracic surgery and the use of minimally invasive procedures whenever feasible.

Comparison of two empirical prolonged infusion dosing regimens for meropenem in patients with septic shock: A two-center pilot study.

BACKGROUND: Due to high pharmacokinetic variability, standard doses of meropenem are frequently inadequate in septic patients. Therapeutic drug monitoring of meropenem is not widely available; therefore, improved empiric dosing recommendations are needed. OBJECTIVES: This study aimed to compare the attainment of pharmacologic targets for two common empirical dosing regimens for meropenem in patients with septic shock. METHODS: Two empiric dosing schemes for meropenem were compared using extended infusions (120 minutes) in 32 patients with septic shock in the intensive care units at two different hospitals. One regimen was 3 × 2 g meropenem/24 h for two days, followed by 3 × 1 g meropenem/24 h; the other regimen was 4 × 1 g meropenem/24 h. Serum meropenem concentrations were measured for the first 72 h of therapy, and pharmacokinetic modelling was performed to define the percentage of time the free drug concentration was above various target MICs for each regimen (%fT>MIC). RESULTS: Both regimens led to a sufficiently high %fT>MIC for pathogens with target MICs < 4 mg/L. When higher MICs were targeted, the %fT>MIC of 4 × 1 g meropenem decreased faster than that of 3 × 2 g meropenem. At high MICs of 32 mg/L, both dosing regimens failed to provide appropriate drug concentrations. Renal function was a significant covariate of target attainment. CONCLUSIONS: The results of this study can guide clinicians in their choice of an empirical dosing regimen for meropenem. If pathogens with low MICs (< 4 mg/L) are targeted, both dosing regimens are adequate, whereas more resistant strains require higher doses.

Anesthesiological considerations in emphysema surgery.

In the last decades, developing thoracic surgery raised the demands for sophisticated anesthesiological management. Especially patients with end-stage thoracic emphysema challenge the anesthesiologist to make modern surgery possible and to provide a safe and effective perioperative management. The development and scientific work-up of single lung ventilation (SLV) laid the cornerstone for surgery of the non-ventilated lung and hemi-thorax. However, modern medicine extended surgical options to extensive tracheal surgery and to patients suffering from severely insufficient lung-capacity precluding single-lung ventilation or artificial ventilation in se. For those critically ill, different techniques were thus developed and evaluated in recent research, among others, non-intubated surgery and surgery under extracorporeal perfusion support that temporarily avoids pulmonary gas exchange and ventilation via the trachea in any way. To tackle postoperative pain with its successive problems of immobilization, insufficient respiration and airway-clearance, regional anesthesia offers great advantages. Thoracic epidural anesthesia (TEA) is considered as the gold standard; complementary, modern ultrasound techniques make regional anesthesia possible even when contraindications prohibit neuraxial blocks. Especially paravertebral block, musculus serratus anterior block, intercostal block and the musculus erector spinae block provide good postoperative pain relief and appear to influence chronic post-thoracotmy pain positively. Careful preoperative preparation, intraoperative monitoring and patient-tailored, individual perioperative management by a well-trained team ensure good results, a good survival and favorable quality of life. This article provides a brief overview over state-of-the-art techniques and future perspectives to provide anesthesia in emphysema surgery.

Physiologically based pharmacokinetic evaluation of cefuroxime in perioperative antibiotic prophylaxis.

AIMS: Adequate plasma concentrations of antibiotics during surgery are essential for the prevention of surgical site infections. We examined the pharmacokinetics of 1.5 g cefuroxime administered during induction of anaesthesia with follow-up doses every 2.5 hours until the end of surgery. We built a physiologically based pharmacokinetic model with the aim to ensure adequate antibiotic plasma concentrations in a heterogeneous population. METHODS: A physiologically based pharmacokinetic model (PK-Sim® /MoBi® ) was developed to investigate unbound plasma concentrations of cefuroxime. Blood samples from 25 thoracic surgical patients were analysed with high-performance liquid chromatography. To evaluate optimized dosing regimens, physiologically based pharmacokinetic model simulations were conducted. RESULTS: Dosing simulations revealed that a standard dosing regimen of 1.5 g every 2.5 hours reached the pharmacokinetic/pharmacodynamic target for Staphylococcus aureus. However, for Escherichia coli, >50% of the study participants did not reach predefined targets. Effectiveness of cefuroxime against E. coli can be improved by administering a 1.5 g bolus immediately followed by a continuous infusion of 3 g cefuroxime over 3 hours. CONCLUSION: The use of cefuroxime for perioperative antibiotic prophylaxis to prevent staphylococcal surgical site infections appears to be effective with standard dosing of 1.5 g preoperatively and follow-up doses every 2.5 hours. In contrast, if E. coli is relevant in surgeries, this dosing regimen appears insufficient. With our derived dose recommendations, we provide a solution for this issue.

Pharmacokinetic characteristics and microbiologic appropriateness of cefazolin for perioperative antibiotic prophylaxis in elective cardiac surgery.

OBJECTIVE: Adequate levels of perioperative antibiotic prophylaxis are essential for prevention of surgical site infections. We examined pharmacokinetic details of 2 g cefazolin administered during induction of anesthesia with repeat dosing shortly after initiation of cardiopulmonary bypass (CPB) in cardiac surgery. METHODS: To identify the microbiologic flora targeted with prophylaxis, pre-, and postoperative swabs were taken from sternal skin. Blood samples for measurement of cefazolin were obtained in 24 patients. Drug levels were used for population pharmacokinetic modeling using Nonmem software (Icon Development Solutions, San Antonio, Tex). RESULTS: More than 90% of bacteria on sternal skin were sensitive to cefazolin, indicating minimal inhibitory concentrations <8 mg/L. All serum levels of cefazolin were above 8 mg/L and might thus effectively prevent infection. Pharmacokinetic modeling in a 1-compartment model predicted a population mean clearance (CL) of 5.23 L/h and a volume of distribution (Vd) of 15.8 L. CPB increased Vd from 14.4 L to 22.1 L with a consecutive reduction to 18 L after the end of extracorporeal circulation. The final model implemented interindividual variability on CL and Vd, incorporating the covariates CPB and albumin on Vd and creatinine clearance on CL. Goodness-of-fit calculations showed that this model adequately describes the data derived from our clinical cohort. CONCLUSIONS: Two grams of cefazolin at induction of anesthesia with a repeat dose after initiation of CPB ensures adequate drug levels to target a majority of pathogens of surgical site infections. Pharmacokinetic modeling demonstrated a significant influence of CPB on the volume of distribution and elimination of cefazolin. Other influences on pharmacokinetic parameters were albumin, protein, and creatinine clearance.