Use of the parenteral antibiotic Ertapenem as short term prophylaxis in bariatric surgery: a pharmaco-kinetic-pharmacodynamic study in class III obese female patients.

BACKGROUND: The objective of this study was to determine the pharmacokinetics-pharmacodynamics (PK/PD) of Ertapenem in extremely obese female patients (Body Mass Index [BMI] ≥ 40 kg/m²) undergoing bariatric surgery. METHODS: Ten patients received 1 g intravenous Ertapenem 0.5 h prior to surgery as short term prophylaxis. Serum Ertapenem concentrations were determined at baseline, at the end of infusion (30 minutes), then at 1, 2, 4, 8, 12 and 24 hours postinfusion. In patients in whom a liver biopsy was necessitated by clinical need, Ertapenem liver concentrations were determined through intraoperative biopsies at 1 and 2 h postadministration. Peritoneal Ertapenem concentrations were determined in drainage fluid samples collected during the 4-8, 8-12, and 12-24 h intervals after Ertapenem administration. A Monte Carlo simulation was performed to estimate the probability of achieving free drug levels above the minimum inhibitory concentration (fT>MIC) for at least 20% and 40% of the dosing interval as PK/PD targets. RESULTS: Peak drug concentration and 24-h area under the concentration-time curve (AUC) were found to be 191.9 ± 37.4 mg/L and 574.3 ± 110.5 mg·h/L, respectively. Ertapenem liver/serum concentration ratios were 6% at 1 h and 5% at 2 h. Drug concentrations in peritoneal fluid were 28.2 ± 6.4 mg/L at 4-8h, declined to 15.2 ± 5.9 at 8-12h and fell further to 4.79 ± 0.2 mg/L at 12-24 h post-administration. The probability to reach the desired PK/PD targets were never reached at any MICs >0.25 µg/mL with a 90% probability. CONCLUSION: Our data suggest that in extremely obese female patients, the standard dose of 1 g i.v. Ertapenem as short term prophylaxis may not provide optimal clinical levels of free drug for prevention of surgical site infections.

Preoperative medication with oral morphine sulphate and postoperative pain.

BACKGROUND: The administration of an analgesic drug prior to nociceptive surgical stimulus could result in a better postoperative pain management. The aim of this study was to evaluate the effect of preoperative oral morphine sulphate on postoperative pain relief. METHODS: Sixty patients undergoing major abdominal surgery were randomly assigned to premedication with 0.5 mg/kg oral morphine sulphate (oral morphine group) or 0.05 mg/kg oral midazolam (active placebo group). Primary outcome was efficacy of morphine premedication on opioid administration of IntraVenous Patient Controlled Analgesia (IVPCA) doses, at 4, 24, and 48 hours after completion of surgery and reducing static and dynamic visual analogue scale (sVAS and dVAS) scores. Secondary outcome was the time needed for the recovery of canalization of the gastro-intestinal tract. It was also evaluated fentanyl intraoperative consumption. Statistical analysis was performed by linear regression and student t test. Values of P<0.05 were considered significant. RESULTS: The two groups were comparable with respect to patient characteristics. At 24 and 48 hours post surgery, administered IVPCA doses were reduced in the oral morphine group compared to the active placebo group (P<0.05). Values of sVAS and dVAS were significantly lower in the oral morphine group compared to the active placebo group at all assessment times (P<0.05). Fentanyl consumption was similar in both groups. Needs of a ketorolac rescue dose was greater in the ap versus the om group (21 patients in the ap vs 9 patients in the om group, P<0.001). Mean gastrointestinal canalization did not significantly differ between groups. CONCLUSIONS: In major abdominal surgery, premedication with oral morphine sulphate produces better postoperative pain control and has an opioid-sparing effect without delaying gastrointestinal canalization time.

Pathophysiology of sepsis in the elderly: clinical impact and therapeutic considerations.

The aging world population will increase the incidence and mortality of severe sepsis. The aim of the present article is to review the pathophysiological differences in sepsis and its clinical impact on the elderly. The impact of immunosenescence on innate and acquired immunity is associated with relative immunologic depression that may favor the spreading of inflammation. Elderly patients also have enhanced apoptotic pathways that may contribute to the incidence of mortality due to sepsis. The inflammation-coagulation network is activated by age, explaining the success of some specific therapies. The initial clinical picture of sepsis in the elderly may be ambiguous but the specific pathopysiological changes of aging increase the risk of a sudden deterioration to severe sepsis with the development of a serious cardiovascular dysfunction. The reduced stress tolerance characteristic of aged tissues explains the high incidence of multi-organ failure in such patients. The specific pathophysiological and clinical picture of sepsis underlies the increased mortality in such patients and prompts research on therapeutic strategies with particular benefits to elderly septic patients.