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Potential role of poly(adenosine 5'-diphosphate-ribose) polymerase activation in the pathogenesis of myocardial contractile dysfunction associated with human septic shock.

Objective:Sepsis is associated with increased production of superoxide and nitric oxide, with consequent peroxynitrite generation. Cardiodepression is induced in the heart during oxidative stress associated with septic shock. Oxidative and nitrosative stress can lead to activation of the nuclear enzyme poly(adenosine 5′-diphosphate [ADP]-ribose) polymerase (PARP), with subsequent loss of myocardial contractile function. The aim of the study was to investigate whether cardiodepression found in septic patients is associated with plasma markers of myocardial necrosis and with myocardial PARP activation. Design:Prospective and observational study. Setting:University hospital intensive care unit for clinical and surgical patients. Patients:Twenty-five patients older than 18 yrs presenting with severe sepsis or septic shock. Patients with history of chronic heart failure, cancer, coronary artery disease, diabetes, or acquired immune deficiency syndrome were excluded. Interventions:Patients were followed for 28 days, and biochemical and hemodynamic data were collected on days 1, 3, and 6 of sepsis. The groups were survivors and nonsurvivors, defined only after the end of clinical patient evolution. Heart sections from patients who died were analyzed with hematoxylin-eosin and Picro Sirius-Red immunostaining and with electron microscopy. Measurements and Main Results:The study population included 25 individuals, of whom 12 (48%) died during the 6 days of follow-up. The initial data of the inflammation marker C-reactive protein and Acute Physiologic and Chronic Health. Evaluation severity were similar in both groups (nonsurvivors, 26 ± 2; survivors, 24 ± 5; NS). Overall, an increase in plasma troponin level was related to increased mortality risk. In patients who died, significant myocardial damage was detected, and histologic analysis of heart sections showed inflammatory infiltration, increased collagen deposition, and derangement of mitochondrial cristae. Immunohistochemical staining for poly(ADP-ribose) (PAR), the product of activated PARP, was demonstrated in septic hearts. There was a positive correlation between PAR staining densitometry and troponin I (r2 = 0.73; p < .05), and the correlation of PAR staining densitometry and left ventricular systolic stroke work index was r2 = 0.33 (p = .0509). Conclusion:There is significant PARP activation in the hearts of septic patients with impaired cardiac function. We hypothesize that PARP activation may be partly responsible for the cardiac depression seen in humans with severe sepsis.

Evaluation of a minimal sedation protocol using ICU sedative consumption as a monitoring tool: a quality improvement multicenter project

IntroductionOversedation frequently occurs in ICUs. We aimed to evaluate a minimal sedation policy, using sedative consumption as a monitoring tool, in a network of ICUs targeting decrement of oversedation and mechanical ventilation (MV) duration.MethodsA prospective quality improvement project was conducted in ten ICUs within a network of nonteaching hospitals in Brazil during a 2-year period (2010 to 2012). In the first 12 months (the preintervention period), we conducted an audit to identify sedation practice and barriers to current guideline-based practice regarding sedation. In the postintervention period, we implemented a multifaceted program, including multidisciplinary daily rounds, and monthly audits focusing on sedative consumption, feedback and benchmarking purposes. To analyze the effect of the campaign, we fit an interrupted time series (ITS). To account for variability among the network ICUs, we fit a hierarchical model.ResultsDuring the study period, 21% of patients received MV (4,851/22,963). In the postintervention period, the length of MV was lower (3.91 ± 6.2 days versus 3.15 ± 4.6 days; mean difference, -0.76 (95% CI, -1.10; -0.43), P <0.001) and 28 ventilator-free days were higher (16.07 ± 12.2 days versus 18.33 ± 11.6 days; mean difference, 2.30 (95% CI, 1.57; 3.00), P <0.001) than in the preintervention period. Midazolam consumption (in milligrams per day of MV) decreased from 329 ± 70 mg/day to 163 ± 115 mg/day (mean difference, -167 (95% CI, -246; -87), P <0.001). In contrast, consumption of propofol (P = 0.007), dexmedetomidine (P = 0.017) and haloperidol (P = 0.002) increased in the postintervention period, without changes in the consumption of fentanyl. Through ITS, age (P = 0.574) and Simplified Acute Physiology Score III (P = 0.176) remained stable. The length of MV showed a secular effect (secular trend β1β=-0.055, P = 0.012) and a strong decrease immediately after the intervention (intervention β2 = -0.976, P <0.001). The impact was maintained over the course of one year, despite the waning trend for the intervention’s effect (postintervention trend β3 = 0.039, P = 0.095).ConclusionsBy using a light sedation policy in a group of nonteaching hospitals, we reproduced the benefits that have previously been demonstrated in controlled settings. Furthermore, systematic monitoring of sedative consumption should be a feasible instrument for supporting the implementation of a protocol on a large scale.

Is the widening of the QTc associated with mortality in sepsis

The widening of the QTc is a mortality predictor in acute coronary syndromes and cerebral vascular accident.

Acid – base disturbances in critically ill septic patients: a longitudinal quantitative study

Applying a quantitative methodology, we described the acid – base status of severe septic patients in the first 5 days after admission to the ICU.