Kadri Tamme

Translocation of indigenous microflora in an experimental model of sepsis

Translocation of viable bacteria from gut to bloodstream and other sterile body sites during shock has been demonstrated in several experimental and clinical studies. The factors causing translocation and its incidence at different stages of shock are not known. The aim of the study was to evaluate the importance of several factors causing translocation of indigenous microflora in an experimental model of septic shock based on intraperitoneal Escherichia coli sepsis in rats. Counts of inoculated E. coli and translocated bacteria in different locations, gut morphology and haematological values were evaluated at different stages of sepsis. Sepsis developed in all animals and E. coli achieved the highest counts in blood 6 h after inoculation. Translocation was commonest at 6 and 12 h after inoculation. Frequently translocating bacteria were lactobacilli, bifidobacteria, bacteroides and peptostreptococci. In early sepsis, translocation was associated with high E. coli counts in blood, yet in late sepsis the opposite correlation was present. Low infiltration by neutrophils in the ileum and decreased mitotic activity in the colon were associated with a high translocation rate. In early sepsis, translocation was associated with low lymphocyte counts, but in late sepsis, with low neutrophil counts. Translocation of bacteria (including anaerobes) that colonise the gut in high counts takes place during sepsis. Putative influencing factors such as activity of the primary disease (bacterial counts in blood), gut morphology or haematological values seem to have different impacts on translocation, depending on the stage of the disease.

The evidence of oxidative stress in cardiac surgery and septic patients: A comparative study

In present study, lipid peroxidation products (thiobarbituric acid reactive substances (TBARS) and diene conjugates (DC)) and markers of blood antioxidant status (serum antioxidative capacity (AOC) and red blood cells glutathione (RBC-GSH)) were measured to compare the extent of oxidative stress in 12 cardiac surgery and 10 septic general surgery patients. In heart surgery, arterial TBARS were significantly increased 15 min after the start and 15 min after cessation of cardiopulmonary bypass, while AOC at these times was decreased. Eighteen hours after surgery all parameters, except antioxidative capacity, had returned to preoperative levels. In septic patients, the preoperative level of lipid peroxidation was significantly higher and antioxidative capacity lower than in heart surgery patients. Surgery had no influence on oxidative stress markers in this group of patients. Increase in lipid peroxidation and reduction in blood antioxidant capacity, induced either by sepsis or cardiopulmonary bypass, were of comparable extent.

Should we measure intra-abdominal pressures in every intensive care patient?

Intra-abdominal pressure (IAP) is seldom measured by default in intensive care patients. This review summarises the current evidence on the prevalence and risk factors of intra-abdominal hypertension (IAH) to assist the decision-making for IAP monitoring.IAH occurs in 20% to 40% of intensive care patients. High body mass index (BMI), abdominal surgery, liver dysfunction/ascites, hypotension/vasoactive therapy, respiratory failure and excessive fluid balance are risk factors of IAH in the general ICU population. IAP monitoring is strongly supported in mechanically ventilated patients with severe burns, severe trauma, severe acute pancreatitis, liver failure or ruptured aortic aneurysms. The risk of developing IAH is minimal in mechanically ventilated patients with positive end-expiratory pressure < 10 cmH2O, PaO2/FiO2 > 300, and BMI < 30 and without pancreatitis, hepatic failure/cirrhosis with ascites, gastrointestinal bleeding or laparotomy and the use of vasopressors/inotropes on admission. In these patients, omitting IAP measurements might be considered.In conclusions, clear guidelines to select the patients in whom IAP measurements should be performed cannot be given at present. In addition to IAP measurements in at-risk patients, a clinical assessment of the signs of IAH should be a part of every ICU patients bedside evaluation, leading to prompt IAP monitoring in case of the slightest suspicion of IAH development.

Expanded measurements of intra-abdominal pressure do not increase the detection rate of intra-abdominal hypertension: a single-center observational study.

Objective:Intra-abdominal hypertension may contribute to a poor outcome. Whether limiting intra-abdominal pressure measurements to preselected at-risk patients allows for sufficient detection of intra-abdominal hypertension is unclear. We aimed to clarify whether expanded intra-abdominal pressure monitoring results in an increased detection rate of intra-abdominal hypertension. Design:Retrospective observational study. Setting:General ICU of University Hospital. Patients:Consecutive adult ICU patients from 2004 to 2011. Interventions:Intra-abdominal pressure measurements in predefined at-risk patients. Measurements and Main Results:Prospectively collected data of 2,696 admissions were divided into three subgroups according to the intra-abdominal pressure measurement policy in different years: 1) 2004–2005, mechanically ventilated patients with at least one additional risk factor for intra-abdominal hypertension (multiple trauma, abdominal surgery, pancreatitis, post-cardiopulmonary resuscitation, fluid resuscitation > 5 L/24 hr, vasoactive or inotropic support, and renal replacement therapy); 2) 2006–2009, all mechanically ventilated patients expected to stay for more than or equal to 24 hours; and 3) 2010–2011, mechanically ventilated patients with a body mass index greater than 30 kg/m2, positive end-expiratory pressure more than 10 cm H2O, PaO2/FIO2 less than 300, use of vasopressors/inotropes, pancreatitis, hepatic failure/cirrhosis with ascites, gastrointestinal bleeding, or postlaparotomy. In all, 2,696 patients were studied, and 1,241 patients (46.0%) underwent intra-abdominal pressure monitoring. The intra-abdominal pressure was measured in 31.7%, 55.6%, and 41.1% of patients during the first, second, and third time periods (p < 0.001), and intra-abdominal hypertension (intra-abdominal pressure ≥ 12 mm Hg) occurred in 19.9%, 20.3%, and 20.1% of patients, respectively (p = 0.972). The mean intra-abdominal pressure at admission day was an independent predictor of mortality in patients with intra-abdominal pressure measurements started within the first 24 hours (odds ratio, 1.046 [95% CI, 1.019–1.072]). The mortality of patients with intra-abdominal hypertension was 29.8% versus 18.6% in those without intra-abdominal hypertension (p < 0.001). Conclusions:Expanding the measurement of intra-abdominal pressure to more than 50% of intensive care admissions does not increase the detection rate of intra-abdominal hypertension. In patients with intra-abdominal pressure monitoring, the mean intra-abdominal pressure on the admission day is an independent predictor of mortality.

Septic shock with disseminated microfoci in multiple organs in humans

Objective: Histological assessment of tissue damage and localisation of bacteria in autopsy materials of patients who died of septic shock. Design: Prospective observational study. Setting: General and paediatric intensive care units, Tartu University Hospitals and Institute of Anatomy, Tartu University. Patients: 2 patients, who died of septic shock; 1 patient, who died of trauma. Measurements and results: Tissue samples of different organs (lungs, heart, spleen, pancreas, liver, adrenals, kidneys and brain) were studied for the presence of bacteria and for the local inflammatory reaction with light microscopy. Bacteria (cocci) were found in the capillaries and tissues of both septic shock patients, but not in the control patient. Capillary dilatation, oedema, stasis and cell death, but no polymorphonuclear infiltration, were seen around the foci of bacterial invasion. Conclusions: Massive penetration of bacteria into all tissues without significant polymorphonuclear infiltration may take place in severe septic shock.

Pharmacokinetics and pharmacodynamics of piperacillin/tazobactam during high volume haemodiafiltration in patients with septic shock

The purpose of the study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of piperacillin and tazobactam during high‐volume haemodiafiltration (HVHDF).

Pharmacokinetics of doripenem during high volume hemodiafiltration in patients with septic shock

Pharmacokinetics (PK) of doripenem was determined during high volume hemodiafiltration (HVHDF) in patients with septic shock. A single 500 mg dose of doripenem was administered as a 1 hour infusion during HVHDF to 9 patients. Arterial blood samples were collected before and at 30 or 60 minute intervals over 8 hours (12 samples) after study drug administration. Doripenem concentrations were determined by ultrahigh performance liquid chromatography‐tandem mass spectrometry. Population PK analysis and Monte Carlo simulation of 1,000 subjects were performed. The median convective volume of HVHDF was 10.3 L/h and urine output during the sampling period was 70 mL. The population mean total doripenem clearance on HVHDF was 6.82 L/h, volume of distribution of central compartment 10.8 L, and of peripheral compartment 12.1 L. Doses of 500 mg every 8 hours resulted in 88.5% probability of attaining the target of 50% time over MIC for bacteria with MIC = 2 µg/mL at 48 hours, when doubling of MIC during that time was assumed. Significant elimination of doripenem occurs during HVHDF. Doses of 500 mg every 8 hours are necessary for treatment of infections caused by susceptible bacteria during extended HVHDF.

Effects of high volume haemodiafiltration on inflammatory response profile and microcirculation in patients with septic shock.

Background. High volumes of haemofiltration are used in septic patients to control systemic inflammation and improve patient outcomes. We aimed to clarify if extended intermittent high volume online haemodiafiltration (HVHDF) influences patient haemodynamics and cytokines profile and/or has effect upon sublingual microcirculation in critically ill septic shock patients. Methods. Main haemodynamic and clinical variables and concentrations of cytokines were evaluated before and after HVHDF in 19 patients with septic shock requiring renal replacement therapy due to acute kidney injury. Sublingual microcirculation was assessed in 9 patients. Results. The mean (SD) time of HVHDF was 9.4 (1.8) hours. The median convective volume was 123 mL/kg/h. The mean (SD) dose of norepinephrine required to maintain mean arterial pressure at the target range of 70–80 mmHg decreased from 0.40 (0.43) μg/kg/min to 0.28 (0.33) μg/kg/min (p = 0.009). No significant changes in the measured cytokines or microcirculatory parameters were observed before and after HVHDF. Conclusions. The single-centre study suggests that extended HVHDF results in decrease of norepinephrine requirement in patients with septic shock. Haemodynamic improvement was not associated with decrease in circulating cytokine levels, and sublingual microcirculation was well preserved.

Bacterial Dissemination and the Value of Blood Cultures in Patients Who Die of Septic Shock

The aim of this study was to determine whether blood cultures reflect real bacterial dissemination into the tissues of patients who die of septic shock. A total of 20 patients were divided into two groups with surgical (nine) and non-surgical (11) sepsis. Blood cultures were taken and the adequacy of antibacterial therapy was assessed. Postmortem tissue samples of different organs were studied using light microscopy for the presence of bacteria. A semi-quantitative measure, the contamination index, was applied. Despite negative blood cultures from 14 patients, bacteria were found in almost all of the organs examined from all of the patients. There was no difference in contamination index between patients who received adequate antibacterial therapy and those who did not. We conclude that septic shock is the manifestation of bacterial dissemination into the organs, and that blood cultures are of limited value in the diagnosis of sepsis, especially when they are taken during adequate antibacterial therapy.

Dosing of Ertapenem in an Extreme Obesity: A Case Report of 250 kg Patient

Limited available data for dosing in obesity of the medicines used in this case are discussed, with the emphasis on ertapenem. The case illustrates the difficulties in dosing medicines to morbidly overweight patients. The number of such patients is increasing but data on adequate doses of medicines are scarce. We demonstrate that ertapenem 1,5 g i.v. once daily provided adequate drug exposure for susceptible bacteria in a 250 kg patient with normal renal function. The case suggests the usefulness of therapeutic drug monitoring of antibiotics, especially in critically ill patients.