Rescue therapy with polymyxin B hemoperfusion in high-dose vasopressor therapy refractory septic shock.

BACKGROUND: Refractory septic shock (RSS) requiring major vasopressor support is associated with high mortality, especially in Gram-negative infections. The study aim was to describe hemodynamics, organ failure, and clinical outcomes in high-dose vasopressor therapy (HDVT) RSS patients treated with Polymyxin B hemoperfusion (PMX-HP) as rescue therapy. METHODS: We retrospectively analyzed 52 patients, unresponsive to conventional therapy, treated with two sessions of PMX-HP requiring HDVT (norepinephrine and/or epinephrine requirement (NEP+EP) ≥ 0.5 µg/kg/min), ≥ 2 organ failures, and suspected/confirmed Gram-negative infection from any source. RESULTS: At baseline, mean arterial pressure (MAP) was 80 ± 13 mmHg and NEP + EP requirement was 1.11 ± 0.56 µg/kg/min. After two PMX-HP sessions, at 72 h, MAP significantly increased and NEP + EP requirement decreased respectively by 12% and 76%. Pulmonary and renal function also improved significantly. Thirty patients (58%) showed a ≥ 50% reduction in NEP + EP dose within only 24 h after the first PMX-HP session (early responders), and 22 did not or died from irreversible shock in the same time frame (early non-responders). The 30-day hospital mortality was 29%; it was 16% in early responders and 45% in early non-responders. On multivariate analysis, SAPS II score, vasopressin, and central venous pressure significantly affected 30-day hospital mortality. CONCLUSION: This is the first study describing the use of PMX-HP as a rescue therapy in RSS patients with HDVT and MOF. Our results suggest a possible role for PMX-HP in improving hemodynamics, organ function, and mortality in RSS, with a 30-day survival of up to 70%.

Decreased fluid volume to reduce organ damage: a new approach to burn shock resuscitation? A preliminary study.

OBJECTIVE: To evaluate the impact of decreased fluid resuscitation on multiple-organ dysfunction after severe burns. This approach was referred to as "permissive hypovolaemia". METHODS: Two cohorts of patients with burns>20% BSA without associated injuries and admitted to ICU within 6 h from the thermal injury were compared. Patients were matched for both age and burn severity. The multiple-organ dysfunction score (MODS) by Marshall was calculated for 10 days after ICU admission. Permissive hypovolaemia was administered by a haemodynamic-oriented approach throughout the first 24-h period. Haemodynamic variables, arterial blood lactates and net fluid balance were obtained throughout the first 48 h. RESULTS: Twenty-four patients were enrolled: twelve of them received the Parkland Formula while twelve were resuscitated according to the permissive hypovolaemic approach. Permissive hypovolaemia allowed for less volume infusion (3.2+/-0.7 ml/kg/% burn versus 4.6+/-0.3 ml/kg/% burn; P<0.001), a reduced positive fluid balance (+7.5+/-5.4 l/day versus +12+/-4.7 l/day; P<0.05) and significantly lesser MODS Score values (P=0.003) than the Parkland Formula. Both haemodynamic variables and arterial blood lactate levels were comparable between the patient cohorts throughout the resuscitation period. CONCLUSIONS: Permissive hypovolaemia seems safe and well tolerated by burn patients. Moreover, it seems effective in reducing multiple-organ dysfunction as induced by oedema fluid accumulation and inadequate O2 tissue utilization.

Use of multicomponent, domino, and other one-pot syntheses on solid phase: powerful tools for the generation of libraries of diverse and complex compounds.

The availability of small organic molecules covering as much chemical space as possible is seen as the only means that guarantees potential modulation of the many biological targets that are ultimately being unveiled by genomics. Therefore diversity oriented organic synthesis is rapidly becoming one of the paradigms in the process of modern drug discovery. This has spurred research in those fields of chemical investigation that lead to the rapid assembly of not only molecular diversity, but also molecular complexity. As a consequence multi-component as well as domino or related reactions are witnessing a new spring. Coupling these one-pot processes with solid-phase synthesis offers new perspectives for the preparation of both primary and thematic libraries. The progresses recently made in this field that perfectly suits the needs of modern drug discovery are the subject of the present review.

The influence of length of stay in the ICU on power of discrimination of a multipurpose severity score (SAPS). ARCHIDIA.

OBJECTIVE: To assess how the power of discrimination of a multipurpose severity score (Simplified Acute Physiology Score; SAPS) changes in relation to the length of stay (LOS) in the intensive care unit (ICU). DESIGN: In order to compute the SAPS probability, a model derived from logistic regression was developed in a cohort of 8059 patients. Measures of calibration (goodness-of-fit statistics) and discrimination [receiver operating characteristic (ROC) curve and relative area under the curve (AUC)] were adopted in a developmental set (5389 patients) and a validation set (2670 patients), both randomly selected. Once the logit was developed and the model validated, the whole database (8059 patients) was again assembled. To evaluate the accuracy of first-day SAPS probability over time, area under the ROC curve was computed for each of the initial 10 days of ICU care and for day 15. SETTING: 24 Italian ICUs. PATIENTS: A total of 8059 patients out of 10065 consecutive admissions over a period of 3 years (1990-1992) were included in this study. Patients whose SAPS was not correctly compiled (n = 687), patients younger than 18 years (n = 442), and patients whose LOS was less than 24 h (n = 877) were excluded from this analysis. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The logistic model gave good results in terms of calibration and discrimination, both in the developmental set (goodness-of-fit: chi 2 = 9.24, p = 0.32; AUC = 0.79 +/- 0.01) and in the validation set (goodness-of-fit: chi 2 = 8.95, p = 0.537; AUC = 0.78 +/- 0.01). The AUC for the whole database showed a loss in discrimination closely related to LOS: 0.79 +/- 0.01 at a day 1 and 0.59 +/- 0.02 at day 15. CONCLUSION: The logistic model that we developed meets high standards for discrimination and calibration. However, SAPS loses its discriminative power over time; accuracy of prediction is maintained at an acceptable level only in patients who stay in the ICU no longer than 5 days. The stay in the ICU represents a complex variable, which is not predictable, that influences the performance of SAPS on the first day.

[Hemodynamic and oxygen transport effects of dobutamine in critically ill patients]. / Effetti emodinamici e sul trasporto di ossigeno della dobutamina nei pazienti critici.

The study evaluates the cardiocirculatory and oxymetric effects of dobutamine infusion in doses between 5 and 15 g/kg/min for a period of 48 hours in 18 critical patients of whom 9 with a low cardiac index (mean 2.1) and 9 with a normal or increased cardiac index (mean 3.3). The beta mimetic effect of the drug is particularly evident in the 9 hypodynamic patients who benefited from a 28% increase in the cardiac index. Likewise, oxygen transport and consumption improved by 22% and 15% respectively. In overall terms, the variables which revealed significant modifications were: cardiac index (CI), systolic index (SI), mean pulmonary pressure (MPAP), pulmonary impaction pressure (PAWP), systemic and pulmonary vascular resistance (SVRO), PVRI), oxygen transport and consumption (DO2, VO2) (No major changes were observed in mean arterial pressure (MAP) and heart rate (HR). No tachyphylaxia was noted after 48 hours of continuous infusion.