Stylianos Karatzas

Colistin serum concentrations after intravenous administration in critically ill patients with serious multidrug-resistant, gram-negative bacilli infections: a prospective, open-label, uncontrolled study.

BACKGROUND The emergence of multidrug-resistant nosocomial pathogens, such as Pseudomonas aeruginosa and Acinetobacter baumannii, has led to the revival of the systemic use of antimicrobial agent colistin in critically ill patients, but only limited data are available to define its pharmacokinetic profile in these patients. OBJECTIVE The aim of this study was to assess steady-state serum concentrations of colistin after i.v. administration of colistin methanesulfonate (CMS) in critically ill patients with stable kidney function. METHODS This prospective, open-label, uncontrolled study was conducted at 2 intensive care units in the Athens Trauma Hospital, KAT, Athens, Greece. Adult patients were nonconsecutively enrolled if they were critically ill and had stable kidney function (<0.5 mg/dL change in serum creatinine prior to and until the day of sample collection) and had been receiving CMS as part of a treatment regimen for sepsis irrespective of site of infection with multidrug-resistant, gram-negative bacilli. After i.v. administration of 225-mg CMS (with the exception of 1 patient who received 150 mg) every 8 or 12 hours for at least 2 days, blood samples were collected just before and at 10 minutes and 1, 2, 4, 6, and 8 hours after i.v. infusion (duration, 30 minutes) of the colistin dose on the sampling day. RESULTS Fourteen nonconsecutive patients were enrolled in the study (13 male, 1 female; mean [SD] age, 62.0 [19.2] years; mean [SD] estimated weight, 72.5 [8.5] kg; mean [SD] Acute Physiology And Chronic Health Evaluation II score on admission, 17.1 [6.0]). At steady state, mean (SD) colistin maximum and minimum concentrations were 2.93 (1.24) and 1.03 (0.44) mg/L, respectively, while mean (SD) apparent total body clearance, apparent volume of distribution, and t(1/2) were 13.6 (5.8) L/h, 139.9 (60.3) L, and 7.4 (1.7) hours, respectively. Colistin-related nephrotoxicity was not observed in the study patients. CONCLUSION CMS dosage regimens administered to these critically ill adult patients were associated with suboptimal Cmax/MIC ratios for many strains of gram-negative bacilli currently reported as sensitive (MIC, < or = 2 microg/mL).

Efficacy of CPR in a general, adult ICU

AIM To investigate the initial cardiopulmonary resuscitation (CPR) success rate and long term survival in an Intensive care unit (ICU) population. PATIENTS All patients with cardiac arrest over a 2-year-period (1999-2000) in a general, adult ICU of a general hospital of Athens. METHODS Retrospective collection of clinical data concerning patients, CPR characteristics and survival rates. RESULTS We examined 111 ICU patients, aged 56.4+/-1.9 years (72 males). SAPS II score was 43.9+/-3.8. CPR was performed in 98.2% of the patients within 30 s. Initial restoration of cardiac function (RCF) and successful CPR rate was 100% while 24 h survival was 9.2%. Survivors at 24 h were younger, mainly males, with lower SAPS II score, mainly with pulmonary disease, ventricular fibrillation or ventricular tachycardia (8/10) and initial pupil reactivity (5/10). Four patients required more than one cycle of CPR. Survival to discharge was zero. CONCLUSION Although the initial successful CPR rate in ICU patients may be high, long term survival and hospital discharge is disappointing. Although ICU patients are better monitored and treated in a timely fashion, they are disadvantaged by chronic underlying diseases, severe current medical illnesses and multi organ dysfunction syndrome (MODS) leads to worst outcome after CPR compared with in-ward patients.

The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis: another point of view

We read with interest the paper by Tugrul et al. [1] regarding the effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis managed in their intensive care unit. Apart from the global interest of reading a paper in the field of the treatment of severe sepsis and septic shock, we have an almost similar project in progress. It is well known that the immunotherapy in sepsis is still a gray zone, and it will remain so as long as the relevant literature presents conflicting results [2]. From our understanding and the interim analysis of our data, it seems that we could expect some definitive immunotherapy informationin the near future. In our study, we have presently included 34 patients in the treatment group (IgM + IgG + IgA) and 34 in the control group. Analyzing our data in a manner comparable with that of Tugrul et al. [1], we reach a different conclusion regarding the results. The only difference that exists between our protocol and that of Tugrul et al. regarding the study design and the inclusion criteria is that we include only adults older than 18 years old (the lower age limit of Tugrul et al.s study is 10 years, and adolescents are probably included). The number of patients needed per arm of the study in order to achieve a safe conclusion (statistical power analysis, 80%; P < 0.05 for a mortality decrease of 17%, which was the mortality decrease in our preliminary analysis) is 120 patients in each arm. In a study with a smaller number of patients, therefore, such as those of Tugrul et al. (21 patients in each arm) or ourselves (34 patients in each arm to the present time), any conclusion may be unsafe. Although the data in both studies (in our opinion) are so far not sufficient, a significant difference trend is recorded. The mean age in Tugrul et al.s study is 42.0 ± 18 years in the IgM + IgG + IgA group and 49.3 ± 20.6 years in the control group. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score in that same study is 10.5 ± 4.6 in the IgM + IgG + IgA group and 14.0 ± 8.5 in the control group. Although there is no statistically significant difference, there is a strong tendency for the two means to become different (P = 0.10). In our preliminary data analysis, the mean age is 50.5 ± 3.33 years in the IgM + IgG + IgA group and 50.7 ± 7.36 years in the control group. The APACHE II score in our study is 21.27 ± 7.23 in the IgM + IgG + IgA group and 23.5 ± 7.91 in the control group. The 28-day mortality rate in Tugrul et al.s study is 23.8% in the IgM + IgG + IgA group versus 33.3% in the control group. In our preliminary data analysis, the mortality rate is 22.35% and 40.0% in the IgM + IgG + IgA group and the control group, respectively. Although this difference is a statistically significant one, the analysis of the mortality rate of the subgroups according to the APACHE II scoring of inclusion to the study day is more interesting. The mortality rate in our preliminary data for the IgM + IgG + IgA group with an APACHE II score ranging between 20 and 29 was 22.22%, and that of the control group with the same APACHE II score range was 55%. As we pointed out earlier, in order to demonstrate the clinical effectiveness of immunotherapy in severe sepsis and septic shock, a number of 120 patients is necessary to be included in each arm of our study. Using our preliminary results in the same manner as those in Tugrul et al.s paper [1], we could conclude that it is sometimes possible to present the data in such a way resulting in delusive conclusions. Analyzing the data by means of definitions of sepsis and septic shock, and assuming the patients to be a uniform group, we cannot demonstrate the special subgroups of patients in whom the administration of IgM-enriched immunoglobulin preparations may have highly beneficial effects. By grouping the patients according to some characteristics (such as APACHE II score or Simplified Acute Physiology Score IIscore), the beneficial effect of immunoglobulins could be shown. Using such an approach, a beneficial effect of IgG immunotherapy in a special subgroup of septic patients has already been shown in the study by Dominioni et al. [3]. In conclusion, it seems that there is a subgroup of patients with severe sepsis or septic shock in which the delivery of IgM-enriched immunoglobulin preparations may have a beneficial effect. Further study with more patients, either in our study or that of Tugrul et al., is necessary before we decide whether to use this type of immunotherapy in the treatment of severe sepsis.

Complications, thrombophlebitis rates, and intravenous catheter replacement strategies

A prospective cohort study by Grune et al. [1], recently published in your well-regarded journal, concerned phlebitis rates and time kinetics of short peripheral intravenous catheters. In this very interesting study with a large number of patients, a phlebitis rate of 27.1 per 100 patients and 104 per 1,000 catheter days was reported. Also reported was an increasing incidence of phlebitis related to the duration of catheter placement and that the daily risk for phlebitis is approximately 10–15% from day 1 to day 7. The final conclusion was that the elective catheter change on day 3 according to CDC guidelines [2] should be reevaluated provided that there is a daily inspection of the catheter site for complications to prevent patient discomfort and additional costs. This conclusion was based on the finding that there was no steeper increase in infection risk after the 3rd day of use [3]. However, several questions have been raised regarding this paper including the methods applied for the maintenance of catheter patency and thrombophlebitis prevention. Specifically, it is not mentioned whether an intermittent flushing solution was used in locked catheters between each catheter use and which solution was used, which could influence catheter “life-days” without complications. Also not mentioned was whether patients were concomitantly receiving low molecular weight heparin (LMWH) subcutaneously, which could also influence the occurrence of phlebitis rates. In addition, this study analyzes the incidence of phlebitis as a complication but not all types of complications, and thus it may underestimate the need for catheter replacement due to other reasons including a dysfunctional catheter and accordingly the CDC guidelines for elective replacement on day 3. Finally, as mentioned in the editorial comment on this manuscript [3], there is a high risk of 30% for phlebitis development on day 4 which may justify the routine catheter replacement on day 3 or may indicate an infection control problem in that institution. We recently published a paper on the epidemiology of peripheral vein complications and the evaluation of the efficiency of differing methods for the maintenance of catheter patency and thrombophlebitis prevention in 300 postoperative orthopedic patients with a mean age of 49.2 ± 1.3 years (SEM) in our institution [4]. We found total complication rates of 36 per 100 patients but only 67.3 per 1,000 catheter days. However, the peak of complications was observed on day 3 and 71% of all complications was observed until day 5. Phlebitis rates were only eight per 100 patients and 14.9 per 1,000 catheter days, which are significantly lower compared to the study of Grune et al [1]. These data show that > 1/3 of the patients may experience complications associated with the placement of peripheral intravenous catheters and most of them until day 5 but only a small number of patients may experience thrombophlebitis while receiving LMWH sc for deep vein thrombosis (DVT) prophylaxis. Interestingly, we found that complications were related to the method used for the maintenance of catheter patency and thrombophlebitis prevention. Total complication rates were 30 per 100 patients and 51.6 per 1,000 catheter days in the heparin solution group (3 ml of 100 U/ml heparin in normal saline 0.9%), 46 per 100 patients and 93.7 per 1,000 catheter days in the normal saline group (3 ml of normal saline 0.9%) and 32 per 100 patients and 64.6 per 1,000 catheter days in the control group (catheters were not flushed following catheter use). Thrombophlebitis rates were nine per 100 patients and 15.5 per 1,000 catheter days in the heparin solution group, 11 per 100 patients and 22.4 per 1,000 catheter days in the Infection Correspondence