A.R. De Gaudio

Antioxidant therapy in critically septic patients.

Critical illness and particularly sepsis are associated with a significant redox imbalance resulting from an increased production of oxidant species and a decrease in endogenous antioxidant defences. In critical patients sources of oxidative stress include the mitochondrial respiratory electron transport chain, xanthine oxidase activation, the respiratory burst associated with neutrophil activation, and arachidonic acid metabolism. Several endogenous antioxidants have been identified including enzymes, like superoxide dismutases and glutathione peroxidase, vitamins and other molecules such as uric acid and bilirubin. Recent studies pointed out the correlations between oxidative stress, systemic inflammatory response and apoptosis. Prospective randomized clinical trials regarding antioxidant therapy in critical illness provide increasing evidence in support of selenium, glutamine and omega-3 fatty acids. In particular selenium seems to improve clinical outcome in terms of infections and organ failure, glutamine has been associated with a significant reduction in infectious complications and omega-3 fatty acids could be particularly efficacious in sepsis. Melatonin is a promising molecule that deserves the attention of future research, as well as vitamin C. Further studied should also try to establish the more beneficial combination of antioxidants, as well as the doses, and the timing of administration. When such problems will be resolved hopefully results about antioxidant therapy in critical illness will be more univocal and promising.

Microalbuminuria as an early index of impairment of glomerular permeability in postoperative septic patients

Abstract Objective: To evaluate whether microalbuminuria increases in post-operative patients developing sepsis, and whether it is correlated to the sepsis severity score (SOFA) and the PaO2/FIO2 ratio. Design: Prospective study. Setting: University intensive care unit. Patient population: Fifty-five post-operative ASA II-III patients admitted to the ICU after major abdominal or vascular surgery. Interventions: None. Measurements and results: Urine collection and measurement of microalbuminuria and urinary creatinine on admission and again as soon as sepsis developed or at the end of the study (72 h after admission). Results are expressed as the microalbuminuria/creatinine ratio (MACR). The MACR significantly increased as soon as sepsis (defined according to the ACPP/SCCM Consensus Conference) appeared. The MACR positively correlated to the SOFA score, but had no relation to the PaO2/FIO2 ratio. Patients not developing sepsis did not show any increase in the MACR during the study period. Conclusions: Post-operative patients developing sepsis, unlike those with an uncomplicated post-operative evolution, showed an increase in glomerular permeability which was revealed by MACR. The increase in the MACR was positively correlated to the increase in SOFA score, while it had no relation to the PaO2/FIO2 ratio.

Videolaparoscopic cholecystectomy induces a hemostasis activation of lower grade than does open surgery

AbstractBackground: Tissue injury after trauma and surgery may induce alterations in blood coagulation and fibrinolysis, and the hypercoagulable state observed after surgery can be associated with the risk of postoperative thromboembolic complications. Recently, videolaparoscopic (VLPS) cholecystectomy has been introduced, and its advantages over the open procedure seem related to the reduced surgical trauma. The aim of this study was to investigate hemostatic system alterations in patients who undergo open and VLPS cholecystectomy. Methods: Fibrinogen, prothrombin fragment F1+2, D-dimer, and plasminogen activator inhibitor type-1 (PAI-1) activity was determined in 10 patients who underwent open (group A) and 10 patients who underwent VLPS cholecystectomy (group B), respectively. Blood samples were obtained the day of surgery in the morning (B1), after anesthesia (Aff1), 1 hour after the start of surgery (S1), then 30 min (E.05) and 24 h (E.24) after the surgery. Results: No significant differences were observed in baseline values between groups A and B for the parameters investigated. At 24 h after surgery, fibrinogen increased significantly (p < 0.05) in group A and also was significantly higher than in group B (p < 0.05). In group A, a marked increase in F1+2 levels (p < 0.01) was observed in all the samples, with the maximum values on the first day after surgery (3.7 nmol/l; 1.2–6.0 nmol/l), whereas in group B, a slight but significant increase in F1+2 levels (2.1 nmol/l; 1.1–3.9 nmol/l; p < 0.01) was observed only 30 min after the end of surgery. In both groups A and B, D-dimer markedly increased after surgery, without statistical significant differences between the two groups at any time. The PAI-1 activity plasma levels remained in the normal range during and after surgery in both groups. Conclusions: These results indicate that VLPS surgery induces an activation of the clotting system that, although of low degree and short duration, can lead to a transient prothrombotic state.

Postoperative Atrial Fibrillation

Postoperative atrial fibrillation (POAF) is common among surgical patients and associated with a worse outcome. Pathophysiology of POAF is not fully disclosed, and several perioperative factors could be involved. Direct cardiac stimulation from perioperative use of catecholamines or increased sympathetic outflow from volume loss/anaemia/pain may play a role. Metabolic alterations, such as hypo-/hyperglycaemia and electrolyte disturbances, may also contribute to POAF. Moreover, inflammation, both systemic and local, may play a role in its pathogenesis. Strategies to prevent POAF aim at reducing its incidence and ameliorate global outcome of surgical patients. Nonpharmacological prophylaxis includes an adequate control of postoperative pain, the use of thoracic epidural analgesia, optimization of perioperative oxygen delivery, and, possibly, modulation of surgery-associated inflammatory response with immunonutrition and antioxidants. Perioperative potassium and magnesium depletion should be corrected. The impact of those interventions on patients outcome needs to be further investigated.

Continuous Infusion of Vancomycin in Methicillin- Resistant Staphylococcus Infection

Objective: The aim of the study was to verify the therapeutic response of vancomycin in methicillin-resistant staphylococcus infection (MRSA/MRCNS) administered according to two different methods (intermittent infusion vs. continuous infusion). Method: Experimental plan: retrospective study; study environment: university hospital, two intensive care units. Twenty-five critically ill patients submitted to antibiotic treatment with vancomycin for infection from MRSA/MRCNS were studied. The patients, who were classified according to SAPS II scores, were divided into two groups: group A (n = 14): dose of vancomycin of 0.5 g × 4/day and group B (n = 11): dose of 2 g/day of vancomycin administered in a continuous infusion. Before the antibiotic therapy was started (T1) and prior to its end (T2), the following parameters were evaluated: degree of impairment of the main organs and systems by means of sepsis-related organ failure assessment score (SOFA) and count of the white blood cells (WBC). The length of the hospital stay during intensive care was calculated for both groups (statistics: Student t test). Results: No significant differences were found in the SAPS II scores and in the length of the hospital stay. In a comparison of the T1 and T2 results, we noted that patients of group A had no variations in the SOFA scores (4.84 ± 2.48 vs. 4 ± 3.9) and in the WBC mean values (12,415 ± 5,099 vs. 12,841 ± 6,864 cells/mm3). In contrast, in the patients of group B, we noted significant variations (p < 0.05) in the mean values of the SOFA scores (6.62 ± 2.2 vs. 4.37 ± 3.5) and in the mean values relative to the WBC count (17,242 ± 12,842 vs. 10,757 ± 3,610 cells/mm3). Conclusions: In critically ill patients suffering from MRSA/MRCNS infection, vancomycin administration in continuous infusions improved organ function and leukocyte response, but did not seem to modify the overall evolution of the disease.

Pathophysiology of Sepsis in the Elderly : Clinical Impact and Therapeutic Considerations

The aging world population will increase the incidence and mortality of severe sepsis. The aim of the present article is to review the pathophysiological differences in sepsis and its clinical impact on the elderly. The impact of immunosenescence on innate and acquired immunity is associated with relative immunologic depression that may favor the spreading of inflammation. Elderly patients also have enhanced apoptotic pathways that may contribute to the incidence of mortality due to sepsis. The inflammation-coagulation network is activated by age, explaining the success of some specific therapies. The initial clinical picture of sepsis in the elderly may be ambiguous but the specific pathopysiological changes of aging increase the risk of a sudden deterioration to severe sepsis with the development of a serious cardiovascular dysfunction. The reduced stress tolerance characteristic of aged tissues explains the high incidence of multi-organ failure in such patients. The specific pathophysiological and clinical picture of sepsis underlies the increased mortality in such patients and prompts research on therapeutic strategies with particular benefits to elderly septic patients.

Glomerular permeability and trauma: A correlation between microalbuminuria and Injury Severity Score

OBJECTIVE To determine if there is a correlation between an increase in glomerular permeability, the magnitude of trauma, and the severity of illness. DESIGN Prospective study. SETTING Two university hospital intensive care units. PATIENTS Forty consecutive critically ill trauma patients admitted directly to the intensive care unit within 120 mins of their injuries. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS For each patient, urine was collected from the time of admission until 7 am the next day. Within 48 hrs, only one sample of all urine collected (5 mL) was examined for microalbuminuria and urinary creatinine. Results were expressed as the microalbuminuria/urinary creatinine ratio (MACR). The mortality rate in the intensive care unit, Injury Severity Score at the moment of admission, Acute Physiology and Chronic Health Evaluation III score, and Simplified Acute Physiology Score in the first 24 hrs were calculated for each patient. The data were analyzed using the Pearson test for linear regression and Students t-test. During the first 24 hrs after trauma, there was an increase of MACR (6.9 +/- 0.6 mg/mmol) above normal (reference range, <3 mg/mmol) that was positively correlated with Injury Severity Score (31.4 +/- 1.9; r2 = .73, p < .05). However, there was no correlation between MACR, Acute Physiology and Chronic Health Evaluation III score, Simplified Acute Physiology Score, and mortality rate. CONCLUSIONS Patients with trauma show an increase in glomerular permeability during the first 24 hrs after injury. The magnitude of this increase is correlated with the extent of trauma but does not seem significant enough to be predictive of severity of illness and/or outcome.

Cefazolin bolus and continuous administration for elective cardiac surgery: Improved pharmacokinetic and pharmacodynamic parameters

OBJECTIVE Cefazolin (1-2 g bolus at induction possibly repeated after cardiopulmonary bypass) remains the standard for antibiotic prophylaxis in cardiac surgery. Data indicate, however, that it is underdosed with this dosing schedule. A prospective, randomized study comparing intermittent versus loading dose plus continuous infusion for the same total dose of cefazolin was performed to assess which modality is pharmacokinetically and pharmacodynamically advantageous. METHODS Patients received 2 g cefazolin as a starting dose and then were divided into an intermittent group (receiving another 1 g at 3, 9, and 15 hours after the first dose) and a continuous group (continuous infusion started after the first dose, providing 1 g every 6 hours for 18 hours). Cefazolin levels were measured in blood and atria. RESULTS Mean total and calculated free trough concentrations in blood varied greatly among patients in the intermittent group and were lower than those in the continuous group (P < .05 at 15, 18 and 24 hours). For 9 of 10 (90%) patients in the continuous infusion group, the targeted pharmacokinetic and pharmacodynamic goal (time above minimal inhibitory concentration >90%) was achieved, whereas the goal was met for only 3 of 10 (30%) in the intermittent group (P < .05). The mean atrial tissue concentration was also higher with continuous infusion (P < .05). CONCLUSIONS Administration of cefazolin as bolus plus continuous infusion has pharmacokinetic and pharmacodynamic advantages relative to intermittent administration. It provides more stable serum levels, lower interpatient variability, and higher myocardial tissue penetration.

Accuracy of invasive arterial pressure monitoring in cardiovascular patients: an observational study

IntroductionCritically ill patients and patients undergoing high-risk and major surgery, are instrumented with intra-arterial catheters and invasive blood pressure is considered the “gold standard” for arterial pressure monitoring. Nonetheless, artifacts due to inappropriate dynamic response of the fluid-filled monitoring systems may lead to clinically relevant differences between actual and displayed pressure values. We sought to analyze the incidence and causes of resonance/underdamping phenomena in patients undergoing major vascular and cardiac surgery.MethodsArterial pressures were measured invasively and, according to the fast-flush Gardner’s test, each patient was attributed to one of two groups depending on the presence (R-group) or absence (NR-group) of resonance/underdamping. Invasive pressure values were then compared with the non-invasive ones.ResultsA total of 11,610 pulses and 1,200 non-invasive blood pressure measurements were analyzed in 300 patients. Ninety-two out of 300 (30.7%) underdamping/resonance arterial signals were found. In these cases (R-group) systolic invasive blood pressure (IBP) average overestimation of non-invasive blood pressure (NIBP) was 28.5 (15.9) mmHg (P <0.0001) while in the NR-group the overestimation was 4.1(5.3) mmHg (P <0.0001). The mean IBP-NIBP difference in diastolic pressure in the R-group was −2.2 (10.6) mmHg and, in the NR-group −1.1 (5.8) mmHg. The mean arterial pressure difference was 7.4 (11.2) mmHg in the R-group and 2.3 (6.4) mmHg in the NR-group. A multivariate logistic regression identified five parameters independently associated with underdamping/resonance: polydistrectual arteriopathy (P =0.0023; OR = 2.82), history of arterial hypertension (P =0.0214; OR = 2.09), chronic obstructive pulmonary disease (P =0.198; OR = 2.61), arterial catheter diameter (20 vs. 18 gauge) (P <0.0001; OR = 0.35) and sedation (P =0.0131; OR = 0.5). The ROC curve for the maximal pressure–time ratio, showed an optimum selected cut-off point of 1.67 mmHg/msec with a specificity of 97% (95% CI: 95.13 to 99.47%) and a sensitivity of 77% (95% CI: 67.25 to 85.28%) and an area under the ROC curve by extended trapezoidal rule of 0.88.ConclusionPhysicians should be aware of the possibility that IBP can be inaccurate in a consistent number of patients due to underdamping/resonance phenomena. NIBP measurement may help to confirm/exclude the presence of this artifact avoiding inappropriate treatments.

Cardiorenal Syndromes and Sepsis

The cardiorenal syndrome is a clinical and pathophysiological entity defined as the concomitant presence of renal and cardiovascular dysfunction. In patients with severe sepsis and septic shock, acute cardiovascular, and renal derangements are common, that is, the septic cardiorenal syndrome. The aim of this paper is to describe the pathophysiology and clinical features of septic cardiorenal syndrome in light of the actual clinical and experimental evidence. In particular, the importance of systemic and intrarenal endothelial dysfunction, alterations of kidney perfusion, and myocardial function, organ “crosstalk” and ubiquitous inflammatory injury have been extensively reviewed in light of their role in cardiorenal syndrome etiology. Treatment includes early and targeted optimization of hemodynamics to reverse systemic hypotension and restore urinary output. In case of persistent renal impairment, renal replacement therapy may be used to remove cytokines and restore renal function.