Pharmacokinetics of dexmedetomidine during analgosedation in ICU patients.

Dexmedetomidine (DEX) is a fairly new alfa2-agonist which has been increasingly used in recent years for analgosedation, mostly because it offers a unique ability of providing both moderate level of sedation and analgesia without respiratory depression. Despite of many papers published, there are still only a few concerning the PK of the drug given as long-term infusion in ICU patients. The aim of this work was to characterize the population pharmacokinetics of dexmedetomidine and to investigate the potential benefits of individualization of drug dosing based on patient characteristics in the heterogeneous group of medical and surgical patients staying in intensive care unit. This study was performed in the group of 17 males and 10 females patients with a median age of 59.5 years and median body weight of 75 kg. Blood samples for dexmedetomidine assay were collected from arterial catheter, during and after discontinuation of a standard infusion, that ranged from 24 to 102 h. The following covariates were examined to influence dexmedetomidine PK: age, sex, body weight, patients' health status described by Sequential Organ Failure Assessment Score (SOFA), inotropes usage, and infusion duration. The dexmedetomidine PK was best described by a two-compartment model. The typical values of PK parameters were estimated as 27 L for the volume of the central compartment, 87.6 L for the volume of the peripheral compartment, 38.5 L/h (9.2 mL/min/kg for a 70 kg patient) for systemic clearance and 46.4 L/h for the distribution clearance. Those values are consistent with literature findings. We were unable to show any significant relationship between collected covariates and dexmedetomidine PK. This study does not provide sufficient evidence to support the individualization of dexmedetomidine dosing based on age, sex, body weight, SOFA, and infusion duration.

The pharmacokinetics of propofol in ICU patients undergoing long-term sedation.

The aim of this study was to characterize the pharmacokinetics (PK) of propofol in ICU patients undergoing long-term sedation and to assess the influence of routinely collected covariates on the PK parameters. Propofol concentration-time profiles were collected from 29 patients. Non-linear mixed-effects modelling in NONMEM 7.2 was used to analyse the observed data. The propofol pharmacokinetics was best described with a three-compartment disposition model. Non-parametric bootstrap and a visual predictive check were used to evaluate the adequacy of the developed model to describe the observations. The typical value of the propofol clearance (1.46 l/min) approximated the hepatic blood flow. The volume of distribution at steady state was high and was equal to 955.1 l, which is consistent with other studies involving propofol in ICU patients. There was no statistically significant covariate relationship between PK parameters and opioid type, SOFA score on the day of admission, APACHE II, predicted death rate, reason for ICU admission (sepsis, trauma or surgery), gender, body weight, age, infusion duration and C-reactive protein concentration. The population PK model was developed successfully to describe the time-course of propofol concentration in ICU patients undergoing prolonged sedation. Despite a very heterogeneous group of patients, consistent PK profiles were observed. Copyright © 2016 John Wiley & Sons, Ltd.

Discrete movements of foot epithelium during adhesive locomotion of a land snail.

During the adhesive locomotion of land snails a series of short dark transverse bands, called pedal or foot waves, is visible ifa moving snail's ventral surface is observed through a sheet of glass. Moreover, the mucus secreted from the pedal glands and some pedal epithelial cells forms a thin layer which acts as a glue augmenting adherence, while also acting as a lubricant under the moving parts of the snail's foot. The relationships between velocity and the frequency of pedal waves as well as changes in the volume of small air bubbles under foot waves were analyzed by means of digital recordings made through a glass sheet on which the snails were moving. On the ventral surface of a moving snail foot, the adhering parts of the foot constituted about 80% of the total area, while several moving parts only about 20%. The single moving region of the foot (the pedal wave) amounted to about 3% of snail length. The epithelium in the region of the pedal wave was arched above the substrate and was also more wrinkled than the stationary epithelium, which enabled the forward motion of each specific point of epithelium during the passage of a pedal wave above it. The actual area of epithelium engaged by a pedal wave was at least 30% greater than the area of the epithelium as recorded through a glass sheet. In the region of the pedal wave, the tiny subepithelial muscles acting on the epithelium move it up in the front part of the wave, and then down at the end of the wave, operating vertically in relation to the substrate. In the middle part of the wave, the epithelium only moves forward. In summary, during the adhesive locomotion of snails, the horizontal movement of the ventral surface epithelium proceeds as temporally separate phases of upward, forward and downward movement.

The bi-phased course of electrophysiological response of isolated snail intestine on mechanical stimulation.

The transepithelial potential difference and changes of diameter of isolated snail intestine as index of its motility were studied in immersed bath in control conditions and after gentle stimulation by 60 seconds of washing of the intestinal lumen. Immediate depolarization and 20% augmentation of the lumen were observed during the stimulation. After stimulation, additional transient depolarization of the transepithelial potential difference and gradual diminution of intestine lumen back to control values over a period of 20 minutes occurred. The immediate reaction was greatly influenced by the presence of sodium or chloride ion transport inhibitors, however, the late phase of the response was not. It is hypothesized that changes of transepithelial electrogenic ion transport and of intestinal motility during the stimulation mirror the inflow of intestinal content and after completion of stimulation may be related to its storage.

Glycemic profile and effectiveness and safety of insulin therapy in septic patients: is the blood glucose level sufficient?

INTRODUCTION: Hyperglycemia in sepsis is managed by intensive insulin therapy, which can cause hypoglycemia. OBJECTIVES: The aim of the study was to evaluate the glycemic profile as well as safety and effectiveness of a nurse-controlled insulin therapy protocol in patients with severe sepsis and septic shock. PATIENTS AND METHODS: The study included 16 septic patients who died (nonsurvivors) and 61 septic patients who survived. Glycemia was measured every 4 h, and the dose of insulin infusion was adjusted to maintain glycemia of 4.4 mmol/l to 8.3 mmol/l. We analyzed glycemia levels and daily variations, insulin dose, episodes of hypo- and hyperglycemia. RESULTS: Nonsurvivors and survivors had similar mean glycemia levels (7.38 vs. 7.08 mmol/l; p = 0.20) and insulin requirements (median [Me] = 26.9 vs. 23.9 units/d; p = 0.22; Me = 1.7 vs. 1.4 units/h; p = 0.25). Daily glycemia variation (Me = 4.81 vs. 3.03 mmol/l; p <0.001), episodes of hypoglycemia (18.8% vs. 3.3%; p = 0.02), spontaneous severe hypoglycemia (12.5% vs. 0%; p = 0.006) and hyperglycemia (75.0% vs. 45.9%; p = 0.04) were higher and more frequent in nonsurvivors. Three of 5393 blood samples (0.05%) met severe insulin-induced hypoglycemia criteria, and 74.4% of samples met the recommended range of 4.4-8.3 mmol/l. CONCLUSIONS: Patients who died experienced more episodes of hyperglycemia, spontaneous hypoglycemia and greater variation in the daily glycemia level. Daily glycemia variation is more reliable than a mean glycemic level in evaluating glucose homeostasis in septic patients. Few episodes of severe insulin-induced hypoglycemia occurred while using the nurse-controlled insulin therapy protocol.

[Does the coexistence of cancer have an influence on the course of sepsis]. / Czy wspólistniejaca choroba nowotworowa wplywa na ciezkosc przebiegu sepsy.

UNLABELLED: The guidelines for management of sepsis are constantly updated, nevertheless sepsis is still a difficult clinical problem, especially as its treatment often ends in failure. Hospitalized cancer patients diagnosed with sepsis are especially concerned, as sepsis death rate is significant in that group of patients. The aim of the study was to evaluate and compare cancer- and non-cancer patients diagnosed with sepsis. MATERIAL AND METHODS: The medical records of 56 patients diagnosed with sepsis from January 1. 2007 to August 1. 2008 were reviewed retrospectively. Patients were divided into two groups: 1 group--patients with sepsis and cancer (S+N), II group--patients with sepsis without cancer (S). The etiology of sepsis, primary infectious sources, chosen clinical and laboratory parameters and mortality were analysed. RESULTS: 56 patients were involved in the study. The mean age for S+N patients was higher than for group S (61.3 vs. 45.5 years; p = 0.005). The mean APACHE II score value at the day of admission for the whole population was 22.1 +/- 8.8 (8-45), for S+N group--25.3 +/- 10.3 (12-41) and for group S--21.2 +/- 8.3 (8-45) (p = 0.308). The estimated risk of hospital death was retrospectively 43.4%, 53.3% and 39.0%. Patients in group S+N required larger infusion of minimal noradrenaline doses than the other patients (p = 0.015). The mortality rate was 14.3% and was higher in group S+N than in group S (16.7 vs. 13.6%). Mortality was also significantly higher among patients with larger lactate blood concentration (death: 4.6 vs. survival: 1.9 mmol/l; p = 0.020) and greater base deficit (death: -6.79 vs. survival: -2.34 mmol/l; p = 0,0006). Patients of lower mean arterial pressure (60.8 vs. 75.9 mmHg; p = 0.007) and who required larger noradrenaline infusion (0.514 vs. 0.232 microg/kg/min; p = 0.0009) at the day of admission had a significantly higher risk of death. CONCLUSIONS: The analysis did not indicate evidently higher risk of more severe sepsis's course in cancer sepsis patients. However the severity of patients' general condition estimated by the APACHE II score and the mortality in this group of patients was higher (statistically insignificant results). Patients in group S+N required larger minimal doses of noradrenaline and larger infusion of colloid at the day of admission. The mortality was determined by the haemodynamic disturbance and the severity of general condition, rather than the cancer diagnosis per se.

Venous catheter microbiological monitoring. Necessity or a habit?

BACKGROUND: Usefulness and economic aspects of microbiological analysis of central venous catheter (CVC) tips in diagnosis of the catheter-related bloodstream infection (CRBSI). MATERIAL/METHODS: Retrospective study of an adult intensive care unit in a university hospital. Catheter removal was performed when the clinical state of the patient indicated that the catheter could be the source of infection or inflammation was observed at the puncture site. RESULTS: We microbiologically studied 238 CVC tips according to the Maki method and 723 blood samples from 120 septic patients treated during a 21-month period (32.9% of all patients treated in this time period). In 115 cases (48.4%), the tips were positive. Bacteremia was ascertained in 181 blood samples (24.1%), and 168 samples were collected at the time of CVC removal. In blood samples taken from 20 patients (3% of total blood samples), 25 cases of the same pathogens were isolated from CVC tips. In 12 cases, pathogens found in blood and CVC tips were also cultured in other places. In 13 cases (5.5% of tips), CVCs were the source of CRBSI. Positive predictive value (PPV) and negative predictive value reached 11% and 91%, respectively. The total cost of CVC tip monitoring was about 4000 euro. CONCLUSIONS: Our data support the hypothesis that colonization of CVC is rarely responsible for CRBSI. Relatively low PPV renders tips culture useless as a method of diagnosing CRBSI. Based on these results, the routine microbiological monitoring of CVC tips was discontinued to reduce the cost of treatment.

Late diagnosed necrotizing fasciitis as a cause of multiorgan dysfunction syndrome: A case report.

Necrotizing fasciitis is a rapidly progressive, life-threatening soft tissue bacterial infection. We present a serious case of a 43-year-old male who suffered from necrotizing fasciitis of the left leg in whom a delayed diagnosis caused multiorgan dysfunction.Early recognition of important symptoms is essential in the management and surgical debridement of necrotizing fasciitis. Treatment should include comprehensive supportive measures (early goal-directed therapy, adequate ventilation strategy, activated protein C dosage, tight glucose control, steroids, renal replacement therapy) and early antibiotic therapy based on microbiologic monitoring. The pathophysiology and etiologic factors of necrotizing fasciitis are discussed.