Toshio Fukuoka

Effects of norepinephrine on renal function in septic patients with normal and elevated serum lactate levels

Effects of iv norepinephrine (NE) on renal function were investigated retrospectively in 15 patients with hyperdynamic septic shock. All patients had either a low systolic BP less than 80 mm Hg, and/or oliguria less than 0.5 ml/kg-h. We examined their serum creatinine level (SCr), daily urine flow (UF), 24-h creatinine clearance (Ccr), and hemodynamic indices before and during NE infusion. Before NE administration, the patients were divided into those with with a serum lactate level (Lac) less than 20 mg/dl (group A, n = 9) and greater than 20 mg/dl (group B, n = 6). NE was infused continuously at rates between 0.05 and 0.24 microgram/kg.min which increased systolic BP by greater than or equal to 20 mm Hg. Cardiac index was not significantly changed in either group. In group A, NE increased both UF (p less than .05), and systemic vascular resistance index (SVRI) (p less than .01), but did not affect Ccr. In group B, NE did not increase UF nor SVRI, and decreased Ccr significantly (p less than .05). It is concluded that NE increased UF and SVRI only when Lac was in normal range; otherwise, NE reduced renal function. Thus, when administering NE to increase UF, both Lac and renal function should be monitored carefully.

Low-dose intramuscular polymyxin B improves survival of septic rats.

UNLABELLED Polymyxin B (PLB) is a cationic antibiotic that also stoichiometrically neutralizes the lipid A moiety of endotoxin. We examined effects of a small dose of PLB on the mortality of rats with cecal ligation and puncture, on LPS-stimulated nitric oxide (NO) production, and on tumor necrosis factor alpha (TNF alpha) production by isolated rat Kupffer cells. MATERIALS AND METHODS In vivo studies: Cecal ligation and puncture (CLP) was performed under anesthesia in 28 rats. One hour after CLP, either 600 U/kg of PLB or saline was administered intramuscularly every 6 h (PLB group: n = 12; control group: n = 16). Plasma endotoxin was measured at 3 and 24 h after the CLP by the Endospecy test. This was compared with survival. IN VITRO STUDIES Kupffer cells were isolated from the normal rat liver. The cells were incubated with LPS or LPS + PLB. After 24 h, NO and TNF alpha content were measured using the Griess and ELISA methods, respectively. RESULTS Low dose PLB significantly decreased the endotoxin levels at both 3 and 24 h (5.5 +/- 2.1 pg/mL vs. 32.8 +/- 3.6 at 3 h; 26.1 +/- 6.1 vs. 49.1 +/- 5.6 at 24 h (p < .05) after CLP. PLB significantly improved survival of CLP rats (68.8% in the control group vs. 100% in the PLB treated group on 3 days after CLP, p < .001). PLB also attenuated NO and TNF alpha production from the Kupffer cells. CONCLUSION Intramuscular PLB administered in low doses may improve the mortality of sepsis.

Effects of different triggering systems and external PEEP on trigger capability of the ventilator

ObjectiveThe triggering capability of both the pressure and flow triggering systems of the Servo 300 ventilator (Siemens-Elema, Sweden) was compared at various levels of positive end-expiratory pressure (PEEP), airway resistance (Raw), inspiratory effort and air leak, using a mechanical lung model.DesignThe ventilator was connected to a two bellows-in-series-type lung model with various mechanical properties. Lung complicance and chest wall compliance were 0.03 and 0.12 l/cmH2O, respectively. Raw was 5, 20 and 50 cmH2O/l/s. Respiratory rate was 15 breaths/min. To compare the triggering capability of both systems, the sensitivity of pressure and flow triggered pressure support ventilation (PSV) was adjusted to be equal by observing the triggering time at 0 cmH2O PEEP and 16 cmH2O of pressure support (PS) with no air leak. No auto-PEEP was developed. In the measurement of trigger delay, the PS level ranged from 16 to 22 cmH2O to attain a set tidal volume (VT) of 470 ml at a Raw of 5, 20 and 50 cmH2O/l/s. The PEEP level was then changed from 0, 5 and 10 cmH2O at a PS level of 17 cmH2O and Raw of 5 and 20 cmH2O/l/s, and the trigger delay was determined. The effect of various levels of air leak and inspiratory effort on triggering capability was also evaluated. Inspiratory effort during triggering delay was estimated by measurements of pressure differentials of airway pressure (Paw) and driving pressure in the diaphragm bellows (Pdriv) in both systems.Measurements and resultsThere were no significant differences in trigger delay between the two triggering systems at the various PEEP and Raw levels. At the matched sensitivity level, air leak decreased trigger delay in both systems, and additional PEEP caused auto-cycling. A low inspiratory drive increased trigger delay in the pressure sensing system, while trigger delay was not affected in the flow sensing system. The Paw and Pdriv differentials were lower in flow triggering than in pressure triggering.ConclusionsWith respect to triggering delay, the triggering capabilities of the pressure and flow sensing systems were comparable with and without PEEP and/or high air-way resistance at the same sensitivity level, unless low inspiratory drive and air leak were present. In terms of pressure differentials, the flow triggering system may require less inspiratory effort to trigger the ventilator than that of the pressure triggering system with a comparable triggering time. However, this difference may be extremely small.

The Latent Risk of Acidosis in Commercially Available Total Parenteral Nutrition (TPN) Products: a Randomized Clinical Trial in Postoperative Patients

To evaluate the latent risk of acidosis in commercially available total parenteral nutrition (TPN) products, three types of commercially available TPN products were compared in postoperative patients. Sixty-four hospitalized patients with gastro-intestinal disease who undertook curative gastro intestinal resection were studied prospectively and administered with TPN solutions. Three types of commercially available TPN products were assigned randomly to eligible patients. Serial studies of blood acid-base status, serum electrolytes, and urinary acid-base status were conducted in the three groups administered with different TPN solutions. Patients received appropriate electrolytic solutions on the operation day and TPN solution from 2 to 7 days after operation. There were no differences among any of the serum electrolytes in the three groups. In one group, urinary pH decreased slightly and urinary net acid excretion (NAE) increased significantly after administration. This TPN product contains about 40 mEq/L of non-metabolizable acid to avoid the Maillard reaction that produces a complex of glucose and amino acids. Urinary NAE did not change in the other two groups. These TPN products do not use non-metabolizable acid to adjust pH. The present results suggest that the non-metabolizable acid may be a risk factor of metabolic acidosis.

Difference in the Recognition for Medicine Use by Physicians and Chief Physicians in ICU

In general, medical staff members do their utmost to select appropriate medicines for each patient whenever possible. When choosing medicines, pharmacists have to provide medical staff members and patients with high quality information. However, it is often difficult to select the optimal medicine for patients. When physicians in Intensive Care Unit (ICU) and chief physicians select medication, how do they obtain mutual consent, and what kind of drugs are readily provided by mutual agreement ? We tried to investigate this point using a questionnaire against given to both physicians and chief physicians in ICUs.Physicians in ICU and chief physicians were requested to fill in questionnaires regarding how they selectinjection preparations in terms of purpose, reason and expectations of efficacy in order to inject preparations which are used with high frequency in ICU.As a result, three factors when selecting injection preparations were found to vary among the physicians depended on the medications. These three factors were closely correlated with the injection preparations for the circulatory system since it was easy to evaluate their effects. However, when selecting dopamine and furosemide (20mg), disagreements often arouse even when there was agreement on the purpose and expectations of the drug.The effects of other injection preparations are difficult for physicians in ICU and chief physicians to evaluate because they are often used for different purposes. For example, pirenzepin was found to be continually used even though its effects were unclear.These results suggest that purposes and reasons for using injection preparations and the expectations of efficacy do not always correlate between ICU physicians and chief physicians, even though they may hold a meeting to discuss such drug selection in the ICU. As a results, it is important that pharmacists provide information based on evidence for selecting medicines in order to promote the appropriate and rational use of medicines in ICU.