Danilo Teixeira Noritomi

Evolutive standard base excess and serum lactate level in severe sepsis and septic shock patients resuscitated with early goal-directed therapy: still outcome markers?

PURPOSE To compare the evolution of standard base excess and serum lactate level between surviving and non surviving patients with severe sepsis and septic shock resuscitated with early goal-directed therapy. METHODS This is a retrospective study in an intensive care unit of a university tertiary hospital where 65 consecutive severe sepsis and septic shock patients were observed without any intervention in the treatment by the authors of this report. RESULTS In our study, the mortality of severe sepsis and septic shock patients was 38%. The central venous oxygen saturation of both groups was above 70% after the resuscitative period, excluding the second day of the non survivors group (69.8%). After the second day, the central venous oxygen saturation was significantly higher in the survivors group (P < .001). Standard base excess was initially low in both groups, but from the second day on, the correction of standard base excess was significantly more successful and linear in the survivor group (P < .001). Lactate levels were similar during the evolution of both groups. CONCLUSIONS Although evolutive standard base excess and serum lactate level are still outcome markers in severe sepsis and septic shock patients resuscitated with early goal-directed therapy, other studies must be performed to clarify if hemodynamic interventions based on standard base excess and serum lactate level could be reliable to improve clinical outcomes in severe sepsis and septic shock patients.

The use of sodium-chloride difference and chloride-sodium ratio as strong ion difference surrogates in the evaluation of metabolic acidosis in critically ill patients

PURPOSE Inorganic apparent strong ion difference (SIDai) improves chloride-associated acidosis recognition in dysnatremic patients. We investigated whether the difference between sodium and chloride (Na(+)-Cl(-)) or the ratio between chloride and sodium (Cl(-)/Na(+)) could be used as SIDai surrogates in mixed and dysnatremic patients. PATIENTS AND METHODS Two arterial blood samples were collected from 128 patients. Physicochemical analytical approach was used. Correlation, agreement, accuracy, sensitivity, and specificity were measured to examine whether Na(+)-Cl(-) and Cl(-)/Na(+) could be used instead of SIDai in the diagnosis of acidosis. RESULTS Na(+)-Cl(-) and Cl(-)/Na(+) were well correlated with SIDai (R = 0.987, P < 0.001 and R = 0.959, P < 0.001, respectively). Bias between Na(+)-Cl(-) and SIDai was high (6.384 with a limit of agreement of 4.463-8.305 mEq/L). Accuracy values for the identification of SIDai acidosis (<38.9 mEq/L) were 0.989 (95% confidence interval [CI], 0.980-0.998) for Na(+)-Cl(-) and 0.974 (95% CI, 0.959-0.989) for Cl(-)/Na(+). Receiver operator characteristic curve showed that values revealing SIDai acidosis were less than 32.5 mEq/L for Na(+)-Cl(-) and more than 0.764 for Cl(-)/Na(+) with sensitivities of 94.0% and 92.0% and specificities of 97.0% and 90.0%, respectively. Na(+)-Cl(-) was a reliable SIDai surrogate in dysnatremic patients. CONCLUSIONS Na(+)-Cl(-) and Cl(-)/Na(+) are good tools to disclose SIDai acidosis. In patients with dysnatremia, Na(+)-Cl(-) is an accurate tool to diagnose SIDai acidosis.

Characterization of an animal model of severe sepsis associated with respiratory dysfunction

PURPOSE Pathophysiological studies in humans regarding sepsis are difficult to perform due to ethical and methodological concerns. In this context, animal models of sepsis can be useful to better understand this condition and to test therapeutic strategies. The purpose of this study was to characterize a feasible and clinically relevant model of sepsis in pigs that could be useful for testing different therapeutic interventions. METHODS 5 White Large pigs were anesthetized, arterial and pulmonary catheters were introduced, and sepsis was induced by fecal peritonitis. Several biochemical indicators of organ dysfunction and infectious parameters were measured. The pigs were monitored until death, when fragments of organs were removed for pathology. Three animals without peritonitis served as controls and were sacrificed 24 hours after surgery without developing significant changes in organ function. RESULTS Septic pigs survived 17 hours on average (range, 16-18 h), and Escherichia coli was recovered from blood cultures. They developed a significant decrease in left ventricular work and a nonsignificant reduction in mixed venous oxygen saturation. Respiratory dysfunction was characterized by a decrease in the PaO2/FiO2 ratio and respiratory compliance. Pathology of the lungs revealed areas of pulmonary collapse, hemorrhage, pulmonary congestion, and discrete neutrophil infiltrate. CONCLUSIONS Fecal peritonitis in pigs is a clinically relevant model of sepsis associated with acute lung injury without direct pulmonary insult. This model may prove to be useful for studying pathogenic aspects of secondary lung injury as well as for validating ventilatory or pharmacologic interventions.

Impact of Plasma-Lyte pH 7.4 on acid-base status and hemodynamics in a model of controlled hemorrhagic shock

OBJECTIVE: Intravenous infusion of crystalloid solutions is a cornerstone of the treatment of hemorrhagic shock. However, crystalloid solutions can have variable metabolic acid-base effects, perpetuating or even aggravating shock-induced metabolic acidosis. The aim of this study was to compare, in a controlled volume–driven porcine model of hemorrhagic shock, the effects of three different crystalloid solutions on the hemodynamics and acid-base balance. METHODS: Controlled hemorrhagic shock (40% of the total blood volume was removed) was induced in 18 animals, which were then treated with normal saline (0.9% NaCl), Lactated Ringers Solution or Plasma-Lyte pH 7.4, in a blinded fashion (n = 6 for each group). Using a predefined protocol, the animals received three times the volume of blood removed. RESULTS: The three different crystalloid infusions were equally capable of reversing the hemorrhage-induced low cardiac output and anuria. The Lactated Ringers Solution and Plasma-Lyte pH 7.4 infusions resulted in an increased standard base excess and a decreased serum chloride level, whereas treatment with normal saline resulted in a decreased standard base excess and an increased serum chloride level. The Plasma-Lyte pH 7.4 infusions did not change the level of the unmeasured anions. CONCLUSION: Although the three tested crystalloid solutions were equally able to attenuate the hemodynamic and tissue perfusion disturbances, only the normal saline induced hyperchloremia and metabolic acidosis.

Reclassifying the spectrum of septic patients using lactate: severe sepsis, cryptic shock, vasoplegic shock and dysoxic shock

Objective The current definition of severe sepsis and septic shock includes a heterogeneous profile of patients. Although the prognostic value of hyperlactatemia is well established, hyperlactatemia is observed in patients with and without shock. The present study aimed to compare the prognosis of septic patients by stratifying them according to two factors: hyperlactatemia and persistent hypotension. Methods The present study is a secondary analysis of an observational study conducted in ten hospitals in Brazil (Rede Amil - SP). Septic patients with initial lactate measurements in the first 6 hours of diagnosis were included and divided into 4 groups according to hyperlactatemia (lactate >4mmol/L) and persistent hypotension: (1) severe sepsis (without both criteria); (2) cryptic shock (hyperlactatemia without persistent hypotension); (3) vasoplegic shock (persistent hypotension without hyperlactatemia); and (4) dysoxic shock (both criteria). Results In total, 1,948 patients were analyzed, and the sepsis group represented 52% of the patients, followed by 28% with vasoplegic shock, 12% with dysoxic shock and 8% with cryptic shock. Survival at 28 days differed among the groups (p<0.001). Survival was highest among the severe sepsis group (69%, p<0.001 versus others), similar in the cryptic and vasoplegic shock groups (53%, p=0.39), and lowest in the dysoxic shock group (38%, p<0.001 versus others). In the adjusted analysis, the survival at 28 days remained different among the groups (p<0.001) and the dysoxic shock group exhibited the highest hazard ratio (HR=2.99, 95%CI 2.21-4.05). Conclusion The definition of sepsis includes four different profiles if we consider the presence of hyperlactatemia. Further studies are needed to better characterize septic patients, to understand the etiology and to design adequate targeted treatments.

Effect of Paco2 variation on standard base excess value in critically ill patients

PURPOSE The aim of this study was to investigate the impact of acute Paco(2) temporal variation on the standard base excess (SBE) value in critically ill patients. METHODS A total of 265 patients were prospectively observed; 158 were allocated to the modeling group, and 107 were allocated to the validation group. Two models were developed in the modeling group (one including and one excluding Paco(2) as a variable determinant of SBE), and both were tested in the validation group. RESULTS In the modeling group, the mathematical model including SIDai, SIG, l-lactate, albumin, phosphate, and Paco(2) had a predictive superiority in comparison with the model without Paco(2) (R(2) = 0.978 and 0.916, respectively). In the validation group, the results were confirmed with significant F change statistics (R(2) change = 0.059, P < .001) between the model with and without Paco(2). A high correlation (R = 0.99, P < .001) and agreement (bias = -0.25 mEq/L, limits of agreement 95% = -0.72 to 0.22 mEq/L) were found between the model-predicted SBE value and the SBE calculated using the Van Slyke equation. CONCLUSIONS Acute Paco(2) temporal variation is related to SBE changes in critically ill patients.

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.

Metabolic acidosis in sepsis.

Metabolic acidosis is very common in critically ill septic patients. Acidosis may be a result of the underlying pathophysiology, but it also may be the result of the way in which those patients are managed. Chloride-associated acidosis is frequent and is potentially aggravated during fluid resuscitation. The severity of metabolic acidosis is associated with poor clinical outcomes; however, it remains uncertain whether or not there is a causal relationship between acidosis and the pathophysiology of septic syndromes. Several experimental findings have demonstrated the impact of acidosis modulation on the release of inflammatory mediators and cardiovascular function. Treatment of metabolic acidosis is based on control of the underlying process and support of organ dysfunction, although the use of intravenous chloride-poor balanced solutions seems an attractive option to prevent the worsening of metabolic acidosis during fluid resuscitation.

Metabolic acid-base status in critically ill patients: is standard base excess correlated with serum lactate level?

BACKGROUND AND OBJECTIVES To correlate standard base excess (SBE) with serum lactate level and demonstrate the independent prognostic significance of each one. METHODS In a retrospective study, we retrieved data from 333 patients of our prospectively collected database of 7-bed medical intensive care unit of a 1800-bed university hospital. RESULTS The results have shown a poor correlation between SBE and lactate, r = - 0.358, p < 0.001, and an independent prognostic significance of each one when analyzed concomitantly, odds ratio (95% Confidence interval) = 0.996 (0.992 - 0.999) to standard base excess and 1.000 (1.000 - 1.002) to lactate at entrance; and odds ratio (95% Confidence interval ) = 0.990 (0.985 - 0.994) to standard base excess and 1.003 (1.001 - 1.005) to lactate after 24 hours. The accuracy of standard base excess was close to lactate to determine in-intensive care unit death. CONCLUSIONS The lactic component of the metabolic acidosis is not the major determinant of standard base excess. Serum lactate and SBE are independent outcome predictors in critically ill patients.

Partitioning evolutive standard base excess determinants in septic shock patients

BACKGROUND AND OBJECTIVES The amount of metabolic acidosis measured through the standard base excess (SBE) has been shown to be an outcome marker and its improvement has been associated with better survival. We studied the mechanism of standard base excess variation in the first three days of intensive care unit (ICU) stay through the evaluation of independent variables of physico-chemical approach. METHODS Data were retrieved from our prospective collected data base from patients with diagnosis of septic shock, daily up to the third day after the ICU admission. Single correlations between SBE and independent variables were performed as well as a mathematical multilinear model was built to disclose the SBE variation determinants. RESULTS We have shown that in septic shock patients the standard base excess variation during the first three days of ICU stay is weakly correlated to strong ion gap (SIG), lactate, creatinin and PaCO2 when individually analyzed. Analyzing concomitantly those independent variables, we built a mathematical model with a stepwise multilinear regression composed by apparent strong ion difference (SIDa), SIG, PaCO2, albumin and diuresis that resulted in a R² coefficient of 0.866 to determine SBE variation. CONCLUSIONS Variations of metabolic acidosis measured through the standard base excess in septic shock patients when analyzed until the third day after intensive care unit admission, is resultant of interaction of several independent determinants as PaCO2, diuresis, SIG, SIDa and albumin.