Morbidly obese patient with non-alcoholic steatohepatitis-related cirrhosis who died from sepsis caused by dental infection of Porphyromonas gingivalis: A case report.

Non-alcoholic steatohepatitis (NASH) is associated with increased risks of developing lifestyle-related diseases including type 2 diabetes, cardiovascular disease and cerebral vessel disease. While the two-hit hypothesis and, recently, multiple parallel hits hypothesis of NASH pathogenesis were proposed, further details have not emerged. Recently, dental infection of Porphyromonas gingivalis (P. gingivalis) has been reported as a critical risk factor for NASH progression, which acts as multiple parallel hits to induce inflammation and fibrogenic responses in steatosis. We describe here a 54-year-old woman who died from sepsis and was diagnosed with NASH. Briefly, her body mass index (BMI) at the age of 35 years old had been 25.6 kg/m(2) , but she became obese after withdrawing into her home at the age of 45 years. Severe obesity continued over 19 years without diabetes mellitus. She was admitted to our hospital due to a sudden disturbance of consciousness. On admission, her BMI was 48.5 kg/m(2) . Computed tomography revealed cirrhotic liver with massive ascites, and laboratory data indicated increased inflammatory responses, renal failure and C grade Child-Pugh classification, suggesting the diagnosis of sepsis. Also, severe periodontal disease was present, because the patient's front teeth fell out easily during intubation. Although the focus of infection was not specified, the oral flora Parvimonas micra, a periodontal pathogen, was detected in venous blood. In spite of intensive care including artificial respiration management and continuous hemodiafiltration, she died on the 43rd day after admission. Surprisingly, P. gingivalis was detected in her hepatocytes. This case may represent the significance of P. gingivalis in the progress to cirrhosis in NASH patients.

Pharmacokinetics and pharmacodynamics of once-daily arbekacin during continuous venovenous hemodiafiltration in critically ill patients.

This study examined the pharmacokinetics of arbekacin during continuous venovenous hemodiafiltration (CVVHDF) and assessed the pharmacodynamics to consider arbekacin dosage adaptation in CVVHDF. Arbekacin was administered by 0.5-h infusion once daily, using a polymethyl methacrylate membrane hemofilter, to three critically ill patients undergoing CVVHDF; the flow rates were 0.8 l/h for the filtrate and 0.6 l/h for the dialysate. The drug concentrations in plasma and in the filtrate-dialysate were determined using a fluorescence polarization immunoassay and analyzed pharmacokinetically. The average sieving coefficient of arbekacin was 0.739 and the average drug clearance by CVVHDF was 1.03 l/h. A pharmacokinetic model with three compartments (1, central; 2, peripheral; 3, filtrate-dialysate side hemofilter) accurately reflected the concentration-time data for both plasma and filtrate-dialysate. The pharmacokinetic model assessed the pharmacodynamic profile of arbekacin once-daily regimens (0.5-h infusions) at filtrate-dialysate flow rates of 1.4 and 2.8 l/h, and demonstrated that only the 150-mg and 200-mg regimens achieved an effective target range for C(max) (9-20 microg/ml), suggesting that empirical dosages lower than the usual 150-200 mg should be avoided in patients undergoing CVVHDF. The minimum regimens needed to achieve an effective pharmacodynamic target for the free C(max)/MIC ratio (>8) were 75 mg for an MIC of 0.5 microg/ml, 200 mg for an MIC of 2 microg/ml, and 400 mg for an MIC of 4 microg/ml. These results will help us to better understand the pharmacokinetics of arbekacin during CVVHDF, while also helping in the selection of the appropriate arbekacin regimens, based on a pharmacodynamic assessment, for patients receiving this renal replacement therapy.

Pharmacokinetics and pharmacodynamics of biapenem in critically ill patients under continuous venovenous hemodiafiltration.

To characterize the PK/PD of biapenem (BIPM) in critically ill patients under continuous venovenous hemodiafiltration (CVVHDF), we conducted a prospective, open-label study in nine adult CVVHDF patients with acute renal failure at the Critical Care Medical Center, Hiroshima Prefectural Hospital. Plasma and filtrate samples were obtained at six time points. The concentrations of BIPM in plasma and filtrate were determined by HPLC. PK parameters were analyzed using Monte Carlo simulation with MIC data. BIPM concentrations in the plasma and CVVHDF filtrate peaked at the end of infusion, and the values were similar. The drug clearance by CVVHDF and non-CVVHDF was 1.28 +/- 0.14 and 9.05 +/- 4.05 L/h, respectively. Monte Carlo simulation showed that the more administration times, there were the higher the probability. In conclusion, a dosing regimen of 300 mg BIPM q8h had a higher probability of therapeutic efficacy than q12h in patients with severe sepsis under CVVHDF.

Early induction of PMX-DHP improves oxygenation in severe sepsis patients with acute lung injury.

Direct hemoperfusion with polymyxin B-immobilized fibers (PMX-DHP) has been widely regarded as a treatment modality for septic shock in Japan. Recently, it was reported that PMX significantly improved the P/F (PaO2/FiO2) ratio in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The aim of this study was to examine whether the phase of sepsis is related to the effects of PMX-DHP treatment on oxygenation in patients with ALI and ARDS. Thirty-four patients who had ALI or ARDS with severe sepsis were included in this study, and split into two groups: a high-risk for septic shock (H-R) group and a septic shock (S-S) group, based on the cut-off value at a mean arterial pressure of 60 mmHg. We analyzed the modified APACHE-II score, the sepsis-related organ failure assessment (SOFA) score, mean blood pressure (mBP), catecholamine index (CAI), P/F ratio, and 28 days mortality before and after PMX-DHP treatment. SOFA and modified APACHE-II scores showed no significant difference between the two groups. In both groups, mBP and CAI increased significantly following PMX-DHP. In the H-R group, P/F ratio increased from 194 +/- 83 to 262 +/- 113 after PMX-DHP treatment, with a statistical significance, whereas no difference was found in the S-S group. There was no difference in the 28 days survival rate between the groups. It was suggested that early introduction of PMX-DHP for severe sepsis may improve oxygenation.

Airway Scope for emergency intubations: usefulness of a new video-laryngoscope.

The Airway Scope (AWS-S100, Pentax, Tokyo, Japan) is a new video-laryngoscope, which has a specially designed blade and a portable, battery-powered, 2.4-inch built-in liquid crystal device (LCD) full-color video screen at the top of the handle. In this study, we tested the usefulness of the AWS for tracheal intubation in acute, urgent situations. Patients admitted to the Advanced Emergency and Critical Care Center at Hiroshima University Hospital and who required orotracheal intubations were prospectively enrolled. Tracheal intubations were performed using the AWS by residents (the novice group) or staff physicians (the experienced group), who received a brief instruction in the AWS. We enrolled 38 patients (23 males, 15 females; age, 60 +/- 19 years). Intubations were attempted by 22 intubators (11 residents and 11 experienced personnel). The durations from inserting the blade via the oral cavity until observing the glottis (T1), inserting the tube into the trachea (T2), and confirming the chest rise (T3) were 22 +/- 15, 34 +/- 21 and 49 +/- 27 sec, respectively. When the results were classified into t experienced and novice groups, T1, T2 and T3 were 17 +/- 10 vs. 26 +/- 17, 32 +/- 23 vs. 36 +/- 20, and 45 +/- 25 vs. 53 +/- 27 sec, respectively (the experienced vs. the novice group, n.s.). These results suggested that the AWS may be a suitable device particularly for less experienced personnel, such as novice Advanced Life Support providers.

Effect of smoke inhalation injury on fluid requirement in burn resuscitation.

The effect of smoke inhalation injury on fluid requirement was assessed retrospectively. A total of 131 burn patients were classified into two groups: burn patients with smoke inhalation injury (Group IB: 73 patients) and burn patients without inhalation injury (Group B: 58 patients). Fluid resuscitation was commenced according to the Parkland formula and the infusion rate was modified to meet the main resuscitation goal of an hourly urine output of 1.0 to 2.0 ml/kg. Regression analyses were performed on the volume of fluid administered during the initial 24 hours after injury by burn size for each group. The linear equations obtained were Y (ml/kg/24 hrs) = 71.0 + 5.08 x %TBSA (Group IB) and Y = 39.7 + 5.14 x %TBSA (Group B). A substantial effect of inhalation injury on fluid requirement was speculated to be reflected in a y intercept difference of about 30 ml/kg/24 hrs. Thus, an increase in the fluid requirement related to the presence of inhalation injury was found to be independent and additional to burn injury.

Circulating blood volume in burn resuscitation.

Circulating blood volume (CBV) was prospectively measured in patients with almost solely smoke inhalation injury (Group I: 10 patients) and in patients with severe cutaneous burn (Group B: 6 patients) consecutively until 96 hours after injury, to assess the effect of either injury on intravascular volume status by the pulse dye-densitometry method. All participants were treated by an ordinary fluid regimen based on the Parkland formula with an hourly urine output of 1.0 to 2.0 ml/kg for the resuscitation endpoint. CBV was also measured in 15 elective surgical patients for a control value (76.7+/-9.0 ml/kg). The level of CBV values in Group I was low, ranging from 54.4+/-6.9 ml/kg to 59.6+/-6.2 ml/kg (from 70.9% to 77.7% of control value), while in Group B from 48.5+/-5.5 ml/kg to 55.6+/-17.3 ml/kg (from 63.2% to 72.5%) until 72 hours after injury. There was no significant difference in CBV values between the two groups throughout the study period. We could elucidate the existence and extent of intravascular volume depletion in spite of optimal fluid treatment in both solely smoke inhalation injury and solely severe cutaneous burn. Almost solely inhalation injury was found to decrease CBV to less than that of severe cutaneous burn, which presumably led to the increased fluid requirement. Concerning the resuscitation endpoint in early burn treatment, this depletion in CBV must be taken in mind. Hourly urine output is speculated to be an effective and practical clue to manage a burn patient within permissive hypovolemia.