The Pharmacokinetic Profile and Bioavailability of Enteral N-Acetylcysteine in Intensive Care Unit.

Background and Objectives: N-acetylcysteine (NAC) is a mucolytic agent used to prevent ventilator-associated pneumonia in intensive care units. This study aimed to evaluate the oral bioavailability of NAC in critically ill patients with pneumonia, isolated acute brain injury and abdominal sepsis. Materials and Methods: This quantitative and descriptive study compared NAC's pharmacokinetics after intravenous and enteral administration. 600 mg of NAC was administered in both ways, and the blood levels for NAC were measured. Results: 18 patients with pneumonia, 19 patients with brain injury and 17 patients with abdominal sepsis were included in the population pharmacokinetic modelling. A three-compartmental model without lag-time provided the best fit to the data. Oral bioavailability was estimated as 11.6% (95% confidence interval 6.3-16.9%), similar to bioavailability in healthy volunteers and patients with chronic pulmonary diseases. Conclusions: The bioavailability of enteral NAC of ICU patients with different diseases is similar to the published data on healthy volunteers.

Are We Meeting the Current Standards of Consent for Anesthesia? An International Survey of Clinical Practice.

BACKGROUND International application of existing guidelines and recommendations on anesthesia-specific informed consent is limited by differences in healthcare and legal systems. Understanding national and regional variations is necessary to determine future guidelines. MATERIAL AND METHODS Anonymous paper surveys on their practices regarding anesthesia-specific patient informed consent were sent to anesthesiologists in Estonia, Latvia, and Lithuania. RESULTS A total of 233 responses were received, representing 36%, 26%, and 24% of the practicing anesthesiologists in Lithuania, Latvia, and Estonia, respectively. Although 85% of responders in Lithuania reported using separate forms to secure patient informed consent for anesthesia, 54.5% of responders in Estonia and 50% in Latvia reported using joint forms to secure patient informed consent for surgery and anesthesia. Incident rates were understated by 14.2% of responders and overstated by 66.4% (P<0.001), with the latter frequently quoting incident rates that are several to tens of times higher than those published internationally. Physicians obtaining consent in the outpatient setting were more satisfied with the process than those obtaining consent on the day of surgery, with 62.5% and 42.6%, respectively, agreeing that the informed consent forms provided a satisfactory description of complications (P=0.03). Patients were significantly less likely to read consent information when signing forms on the day of surgery than at earlier times (8.5% vs. 67.5%, P<0.001). Only 46.2% of respondents felt legally protected by the current consent process. CONCLUSIONS Anesthesia-specific informed patient consent practices differ significantly in the 3 Baltic states, with these practices often falling short of legal requirements. Efforts should be made to improving information accuracy, patient autonomy, and compliance with existing legal standards.

Postoperative complications and mortality after major gastrointestinal surgery.

BACKGROUND AND OBJECTIVE: The incidence of postoperative complications and death is low in the general population, but a subgroup of high-risk patients can be identified amongst whom adverse postoperative outcomes occur more frequently. The present study was undertaken to describe the incidence of postoperative complications, length of stay, and mortality after major abdominal surgery for gastrointestinal, hepatobiliary and pancreatic malignancies and to identify the risk factors for impaired outcome. MATERIAL AND METHODS: Data of patients, operated on for gastro-intestinal malignancies during 2009-2010 were retrieved from the clinical database of Tartu University Hospital. Major outcome data included incidence of postoperative complications, hospital-, 30-day, 90-day and 1-year mortality, and length of ICU and hospital stay. High-risk patients were defined as patients with American Society of Anesthesiologists (ASA) physical status ≥3 and revised cardiac risk index (RCRI) ≥3. Multivariate analysis was used to determine the risk factors for postoperative mortality and morbidity. RESULTS: A total of 507 (259 men and 248 women, mean age 68.3±11.3 years) were operated on for gastrointestinal, hepatobiliary, or pancreatic malignancies during 2009 and 2010 in Tartu University Hospital, Department of Surgical Oncology. 25% of the patients were classified as high risk patients. The lengths of intensive care and hospital stay were 4.4±7 and 14.5±10 days, respectively. The rate of postoperative complications was 33.5% in the total cohort, and 44% in high-risk patients. The most common complication was delirium, which occurred in 12.8% of patients. For patients without high risk (ASA130min, and positive fluid balance >1300mL after the 1st postoperative day, were identified as independent risk factors for the development of complications. CONCLUSION: The complication rate after major gastro-intestinal surgery is high. ASA physical status and revised cardiac risk index adequately reflect increased risk for postoperative complications and worse short and long-term outcome.

Sublingual microcirculatory changes during transient intra-abdominal hypertension--a prospective observational study in laparoscopic surgery patients.

BACKGROUND: Microvascular alterations and intra-abdominal hypertension are both involved in development of organ failure. It is not known whether increased intra-abdominal pressure (IAP) is associated with microcirculatory perfusion derangements. HYPOTHESIS: Transient increase in IAP induced by pneumoperitoneum affects sublingual microcirculation. METHODS: 16 laparoscopic cholecystectomy patients were studied. Sidestream dark field (SDF) imaging was used to evaluate sublingual microcirculation. Microcirculatory videos were done before surgery, at least 15 minutes after initiation of pneumoperitoneum and 1 hour after the pneumoperitoneum. Microcirculation cut-off value for vessels was 20 µm. RESULTS: IAP was held at 12.6 (from 12 to 14) mmHg, mean (SD) duration of pneumoperitoneum was 41 (14) minutes. At the baseline, mean total vascular density was 18.8 (2.6) and perfused vessel density 13.2 (2.9) per mm². Proportion of perfused vessels was 59 (11) % and microvascular flow index 2.2 (0.4). Median (IQR) heterogeneity index was 0.6 (0.4-0.9) and mean De Backer score 13.6 (1.5). Increase in IAP did not cause significant changes in sublingual microcirculatory parameters. CONCLUSIONS: Transiently increased IAP due to pneumoperitoneum does not affect sublingual microcirculatory blood flow and vessel density in patients undergoing laparoscopic surgery. However, the low proportion of perfused vessels indicates the prevalence of perioperative microcirculatory deficiency in these patients.

Moderate intra-abdominal hypertension is associated with an increased lactate-pyruvate ratio in the rectus abdominis muscle tissue: a pilot study during laparoscopic surgery.

BACKGROUND: The development of intra-abdominal hypertension [IAH] in critically ill patients admitted to the ICU is an independent predictor of mortality. In an attempt to find an early, clinically relevant metabolic signal of modest IAH, we investigated abdominal wall metabolite concentrations in a small group of patients undergoing laparoscopic surgery. We hypothesized that elevated intra-abdominal pressure [IAP] due to pneumoperitoneum leads to an increased lactate/pyruvate [L/P] ratio in the rectus abdominis muscle [RAM], indicating anaerobic metabolism. METHOD: Six patients scheduled for elective laparoscopic gastric fundoplication were studied. Two hours before surgery, a microdialysis catheter (CMA 60, CMA Small Systems AB, Solna, Sweden) was inserted into the RAM under local anaesthesia. Catheter placement was confirmed by ultrasound. The microdialysis perfusion rate was set at 0.3 µL/min. Dialysate was collected hourly prior to pneumoperitoneum, during pneumoperitoneum, and for 2 h after pneumoperitoneum resolution. IAP was maintained at 12 to 13 mmHg during the surgery. The glucose, glycerol, pyruvate and lactate contents of the dialysate were measured. RESULTS: The median (interquartile range) L/P ratio was 10.3 (7.1 to 15.5) mmol/L at baseline. One hour of pneumoperitoneum increased the L/P ratio to 16.0 (13.6 to 35.3) mmol/L (p = 0.03). The median pneumoperitoneum duration was 86 (77 to 111) min. The L/P ratio at 2 h post-pneumoperitoneum was not different from that at baseline (p = 1.0). No changes in glycerol or glucose levels were observed. CONCLUSIONS: IAH of 12 to 13 mmHg, even for a relatively short duration, is associated with metabolic changes in the abdominal wall muscle tissue of patients undergoing laparoscopic surgery. We suggest that tissue hypoperfusion occurs even during a modest increase in IAP, and intramuscular metabolic monitoring could therefore serve as an early warning sign of deteriorating tissue perfusion.

Perioperative penetration of metronidazole into muscle tissue: a microdialysis study.

OBJECTIVE: To evaluate the concentration of metronidazole in muscle tissue using microdialysis and to compare it with plasma concentration and in vitro-defined MIC(90) (minimal inhibiting concentration) for the most frequent anaerobic bacteria isolated in our hospital. MATERIALS AND METHODS: Six female patients scheduled for elective gynaecological surgery were included. Exclusion criteria were active inflammatory process and being overweight (BMI more than 30). Microdialysis catheters (CMA 60 catheters with 20 kDa cut-off membrane) were placed into the m. vastus lateralis. The microdialysis perfusion rate was 2 microl/min. To assess in vivo recovery of the drug, retrodialysis with a 5-mg/l solution of metronidazole was performed. Microdialysis and blood samples were collected simultaneously 10 h after metronidazole administration. MIC(90) data were obtained from the database of the microbiology laboratory of the local hospital. RESULTS: Data from five patients were included in analysis. The metronidazole concentration in blood achieved a value of 16.5+/-4.6 mg/l at 30 min (first available data), while in muscle a maximum level of 7.8+/-1.5 mg/l was achieved at 114 min. The mean MIC(90) for the Bacteroides fragilis group was 0.25+/-0.26 mg/l. Data from mean plasma concentrations were fitted into the two-compartmental model and time over MIC(90) and time over four times MIC(90) were calculated, which were 52.1+/-13.5 h and 33.2+/-8.7 h, respectively. The C(max)/MIC(90) ratio was 65.8+/-18.5 for plasma and 31.1+/-6.2 for muscle. CONCLUSION: The present data demonstrate that metronidazole penetrates well into muscle tissue. Muscle tissue concentrations reach values far greater than MIC(90) for the Bacteroides fragilis group and persist at such high levels for at least 10 h.