Clinical review: Hypertonic saline resuscitation in sepsis

The present review discusses the hemodynamic effects of hypertonic saline in experimental shock and in patients with sepsis. We comment on the mechanisms of action of hypertonic saline, calling upon data in hemorrhagic and septic shock. Specific actions of hypertonic saline in severe sepsis and septic shock are highlighted. Data are available that support potential benefits of hypertonic saline infusion in various aspects of the pathophysiology of sepsis, including tissue hypoperfusion, decreased oxygen consumption, endothelial dysfunction, cardiac depression, and the presence of a broad array of proinflammatory cytokines and various oxidant species. The goal of research in this field is to identify reliable therapies to prevent ischemia and inflammation, and to reduce mortality.     

Statins do not improve short-term survival in an oriental population with sepsis

Objectives

The aim of this study was to define the effect of statin on 30-day mortality in an oriental population with sepsis.

Design

We conducted a retrospective study on patients with sepsis at National Taiwan University Hospital from 2001 to 2002. The effects of statins on 30-day mortality were evaluated based on clinical settings. Log-rank test and Cox regression analysis were performed using the proportional hazards assumption.

Results

A total of 763 episodes of sepsis were reviewed; 454 consecutive patients were considered eligible. Among them, 104 (22.9%) took a statin at least 30 days before admission and during sepsis course, whereas the other 350 control (77.1%) did not. There was no significant difference of 30-day sepsis-related mortality between groups (19.2% vs 18.9%, P = .952). Statin treatment was not associated with decreased mortality at 30 days (P = .853; risk ratio, 0.95; 95% confidence interval, 0.53-1.68).

Conclusion

Short-term, sepsis-related mortality in a septic Taiwanese population was not reduced with statin treatment in our study. We concluded that statin therapy may have little effect on the survival of sepsis in oriental people, particularly in Taiwanese.     

Statistical analysis of joint short-term and long-term survival in resuscitation research

OBJECTIVE: To develop statistical tools that use combined initial survival data and post-resuscitation survival data to test the null hypothesis that true, population-wide outcomes following experimental CPR interventions are not different from control. METHOD: A new test statistic, d(2), for evaluating Type 1 error is derived from a bivariate, two-dimensional analysis of categorical initial resuscitation and post-resuscitation survival data, which are statistically independent because they are obtained during non-overlapping periods of time. The d(2) test statistic, which is distributed as a chi-squared distribution, is derived from first principles and validated using Monte Carlo methods of computer simulation for thousands of clinical trials. RESULTS: Under the null hypothesis, the normalized difference in the proportions of patients surviving the initial resuscitation period and the normalized difference in the proportions of such short-term survivors that also survive the post-resuscitation period are jointly distributed in a two-dimensional space as a bivariate standard normal distribution, against which observed intervention and control outcomes can be compared in a test of statistical significance. Typically this two-dimensional approach has greater statistical power to detect true differences, compared to conventional one-dimensional tests. Smaller group sizes (Ns) are usually required to reach statistical significance when both initial survival and post-resuscitation survival are considered together. Such two-dimensional analysis is easily extended to meta-analysis of multiple trials. CONCLUSIONS: A straightforward, easy-to-use bivariate test for Type I errors in statistical inference can be done for resuscitation studies reporting both short-term and long-term survival data. Acceptance of such two-dimensional tests of the null hypothesis, as proposed by Hallstrom, can save time, money, effort, and disappointment in the difficult and sometimes frustrating field of resuscitation research.     

Out-of-hospital cardiac arrest in north-east Germany: increased resuscitation efforts and improved survival

In the years after 1989 major political and socioeconomic changes have taken place in East Germany. In parallel, emergency medical services (EMS) were restructured according to western standards. In Stralsund the EMS was restructured from a single to a two tier system with implementation of a second ambulance base in 1990. The number of household telephone extensions more than doubled. To analyze the effects of these changes, patients receiving advanced life support (ALS) for out-of-hospital cardiac arrest of cardiac origin (OHCA) between 1984 and 1988, and from 1991 to 1997 were studied. Adjusted per 100,000 inhabitants, the number of OHCA patients receiving ALS increased from 11 per year before 1989 to 52 per year after 1990 (P < 0.01). Survival without relevant neurologic defects was achieved in 3.7% (2/53) of patients before 1989 and in 8.1% (22/273) after 1990. Response time of the ALS unit shortened from 11.0 +/- 1.4 to 9.0 +/- 0.4 min (n.s.), while response time of any EMS shortened from 11.0 +/- 1.4 to 6.1 +/- 0.3 min (P < 0.005). Adjusted for observation period and population served, there was a 10-fold increase in the number of resuscitations attempted at home and an 8-fold increase in the absolute number of OHCA survivors without relevant neurological defects. In parallel to socioeconomic changes, the restructuring of the EMS in Stralsund and the rapid expansion of the telephone network led to a significant increase in the number of patients successfully resuscitated from OHCA. If the present results can be transferred to other former socialist countries of East and Middle Europe, they may have important implications for the EMS in these regions.     

Fluid resuscitation influences cardiovascular performance and mortality in a murine model of sepsis

Rationale  Current murine models of sepsis do not account for the effects of aggressive fluid resuscitation on hemodynamics and mortality. Objectives  Evaluate the impact of fluid resuscitation regimens on cardiovascular performance and survival in a murine model of sepsis. Methods  Mice (n = 90) were made septic by cecal ligation and puncture (CLP), and received antibiotics plus Low, Intermediate, or High fluid resuscitation regimens. Stroke volume (SV), cardiac output (CO), and fractional shortening (FS) were measured by echocardiography at predefined time points. Measurements and main results  Baseline echocardiographic measurements were similar in all groups. After CLP, SV and CO decreased early in all groups; High: 57.2 ± 9.2 to 23.9 ± 7.2 μL, and 26.8 ± 4.9 to 13.1 ± 5.8 ml/min; Intermediate: 52.1 ± 7.0 to 21.5 ± 6.6 μL, and 24.9 ± 4.1 to 11.9 ± 3.9 ml/min; Low: 54.0 ± 7.0 to 20.3 ± 5.6 μL, and 25.8 ± 4.0 to 11.3 ± 3.9 ml/min (P < 0.05 for all vs. baseline). With resuscitation there was a dose-dependent improvement in SV and CO (P < 0.05). At 24 h SV and CO were 44.0 ± 13.8 μL and 20.7 ± 8.5 ml/min in the High group, 39.8 ± 12.3 μL and 16.7 ± 6.5 ml/min in the Intermediate group, and 30.1 ± 12.4 μL and 14.0 ± 7.2 ml/min in the Low group. Survival was improved in the High fluid group (75%) compared to the Intermediate (58%) and the Low (35%) resuscitation groups (P < 0.05). Conclusions  In this model, as in human sepsis, the intensity of fluid resuscitation modulates hemodynamic response and mortality. Incorporation of early and aggressive fluid resuscitation can significantly enhances the clinical relevance of murine models of sepsis. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

高渗氯化钠羟乙基淀粉40注射液对创伤性脑损伤患者酸碱平衡的影响

目的:评估高渗氯化钠羟乙基淀粉40注射液对创伤性脑损伤患者酸碱平衡的影响.方法:选择创伤性脑损伤患者30例,随机分为两组,实验组患者在麻醉诱导后、颅骨打开前输注250 mL高渗氯化钠羟乙基淀粉40注射液,对照组患者输注250 mL醋酸林格液,比较两组患者酸碱平衡、血流动力学和血浆电解质的变化情况.结果:输注HTS-HES后15 min BE明显下降,在输注30 min后又恢复至基础水平.输注HTS-HES后中心静脉压、血浆钠离子和氯离了浓度明显升高;血浆其他电解质和酸碱平衡变化不明显.结论:高渗氯化钠羟乙基淀粉40注射液对创伤性脑损伤患者的酸碱平衡影响轻微,对血浆钾离子和钙离子无明显影响.     

Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis

Purpose  

To determine the effect of random assignment to fluid resuscitation with albumin or saline on organ function and mortality in patients with severe sepsis.     

Erythropoietin improved initial resuscitation and increased survival after cardiac arrest in rats

Introduction

Recent data have demonstrated potent cardioprotective and neuroprotective effects of the application of growth hormones like erythropoietin (EPO) after focal cardiac or cerebral ischemia. In order to assess possible benefits regarding survival and resuscitation conditions, EPO was tested against placebo in a model of cardiac arrest in the rat.

Methods

Thirty-four male Wistar rats were randomized into two groups (EPO versus control; n = 17 per group). Under anesthesia, cardiac arrest was induced by asphyxia after neuromuscular blockade. After 6 min of global ischemia, animals were resuscitated by external chest compression combined with epinephrine administration. An intravenous bolus of recombinant human EPO (rhEPO, 3000 UI kg⁻¹ body weight, i.v.) or saline (in control group) was performed 15 min before cardiac arrest, by a blinded investigator. Restoration of spontaneous circulation (ROSC), survival at 1, 24, 48 and 72 h and hemodynamic changes after cardiac arrest were studied.

Results

Survival to 72 h was significantly improved in the EPO group (n = 15/17) compared to the control group (n = 7/17). All the EPO-treated rats were successfully resuscitated whereas only 13 of 17 control animals resuscitated. EPO-treated animals required a significantly smaller dose of epinephrine before resuscitation, compared to control rats. Time course of systolic arterial blood pressure after resuscitation revealed no significant differences between both groups.

Conclusion

EPO, when administrated before cardiac arrest, improved initial resuscitation and increased the duration of post-resuscitation survival.     

Effect of fluid resuscitation on mortality and organ function in experimental sepsis models

Introduction

Several recent studies have shown that a positive fluid balance in critical illness is associated with worse outcome. We tested the effects of moderate vs. high-volume resuscitation strategies on mortality, systemic and regional blood flows, mitochondrial respiration, and organ function in two experimental sepsis models.

Methods

48 pigs were randomized to continuous endotoxin infusion, fecal peritonitis, and a control group (n = 16 each), and each group further to two different basal rates of volume supply for 24 hours [moderate-volume (10 ml/kg/h, Ringer's lactate, n = 8); high-volume (15 + 5 ml/kg/h, Ringer's lactate and hydroxyethyl starch (HES), n = 8)], both supplemented by additional volume boli, as guided by urinary output, filling pressures, and responses in stroke volume. Systemic and regional hemodynamics were measured and tissue specimens taken for mitochondrial function assessment and histological analysis.

Results

Mortality in high-volume groups was 87% (peritonitis), 75% (endotoxemia), and 13% (controls). In moderate-volume groups mortality was 50% (peritonitis), 13% (endotoxemia) and 0% (controls). Both septic groups became hyperdynamic. While neither sepsis nor volume resuscitation strategy was associated with altered hepatic or muscle mitochondrial complex I- and II-dependent respiration, non-survivors had lower hepatic complex II-dependent respiratory control ratios (2.6 +/- 0.7, vs. 3.3 +/- 0.9 in survivors; P = 0.01). Histology revealed moderate damage in all organs, colloid plaques in lung tissue of high-volume groups, and severe kidney damage in endotoxin high-volume animals.

Conclusions

High-volume resuscitation including HES in experimental peritonitis and endotoxemia increased mortality despite better initial hemodynamic stability. This suggests that the strategy of early fluid management influences outcome in sepsis. The high mortality was not associated with reduced mitochondrial complex I- or II-dependent muscle and hepatic respiration.     

Fluid resuscitation in patients with end-stage renal disease on hemodialysis presenting with severe sepsis or septic shock: A case control study

Due to the potential risk of volume overload, physicians are hesitant to aggressively fluid-resuscitate septic patients with end-stage renal disease (ESRD) on hemodialysis (HD). Primary objective: To calculate the percentage of ESRD patients on HD (Case) who received ≥30 mL/Kg fluid resuscitation within the first 6 h compared to non-ESRD patients (Control) that presented with severe sepsis (SeS) or septic shock (SS). Secondary objectives: Effect of fluid resuscitation on intubation rate, need for urgent dialysis, hospital length of stay (LOS), intensive care unit (ICU) admission and LOS, need for vasopressors, and hospital mortality. Medical records of 715 patients with sepsis, SeS, SS, and ESRD were reviewed. We identified 104 Case and 111 Control patients. In the Case group, 23% of patients received ≥30 mL/Kg fluids compared to 60% in the Control group (p < 0.001). There was no significant difference in in-hospital mortality, need for urgent dialysis, intubation rates, ICU LOS, or hospital LOS between the two groups. Subgroup analysis between ESRD patients who received ≥30 mL/Kg (N = 80) vs those who received <30 mL/Kg (N = 24) showed no significant difference in any of the secondary outcomes. Compliance with 30 mL/Kg fluids was low for all patients but significantly lower for ESRD patients. Aggressive fluid resuscitation appears to be safe in ESRD patients.     

In-hospital cardiopulmonary resuscitation: patient, arrest and resuscitation factors associated with survival

Data on 470 adults with single in-hospital cardiac arrest resuscitations were analyzed to determine 24-h and discharge survival rates and to identify significant correlates of survival. One hundred fifty-three (33%) patients were alive 24 h after initiation of cardiopulmonary resuscitation; 69 (45% of 24-h survivors, 15% of all patients) were discharged alive. Logit analysis identified the following independently significant correlates of 24-h survival: arrest locations other than emergency room or cardiac care unit, CPR duration less than 15 min, non-cardiac primary diagnosis, non-asystolic dysrhythmia, less than one intravenous and one drip-administered inotrope and absence of pacemaker insertion and defibrillation. Fifty-one (94%) of 54 patients with all of these characteristics were alive 24 h after initiation of CPR. The same variables, as well as age less than 68 years and absence of intubation were statistically associated with discharge survival. Nine (64%) of 14 patients with all of these characteristics were discharged alive. Increased intervention was generally associated with increased mortality. Overall survival rates replicate previous reports and may reflect the effects of diagnosis-related groups policies on the average illness severity of the in-patient population, rather than failure of current CPR methods to improve the probability of survival. Use of the data as baseline for future studies and as a source of hypotheses for research on decision making are discussed.     

Oleuropein: a novel immunomodulator conferring prolonged survival in experimental sepsis by Pseudomonas aeruginosa

Oleuropein, a novel immunomodulator derived from olive tree, was assessed in vitro and in experimental sepsis by Pseudomonas aeruginosa. After addition in monocyte and neutrophil cultures, malondialdehyde, TNF-alpha, IL-6, and bacterial counts were estimated in supernatants. Acute pyelonephritis was induced in 70 rabbits after inoculation of pathogen in the renal pelvis. Intravenous therapy was administered in four groups postchallenge by one multidrug-resistant isolate (A, controls; B, oleuropein; C, amikacin; D, both agents) and in three groups postchallenge by one susceptible isolate (E, controls; F, oleuropein; G, amikacin). Survival was recorded; bacterial growth in blood and organs was counted; endotoxins (LPS), malondialdehyde, total antioxidant status, and TNF-alpha in serum were estimated. TNF-alpha and IL-6 of cell supernatants were not increased compared with controls when triggered by LPS and P. aeruginosa. Counts of multidrug-resistant P. aeruginosa were decreased in monocyte supernatants. Median survival of groups A, B, C, D, E, F, and G were 3.00, 6.00, 2.00, 10.00, 1.00, 5.00, and 1.00 days, respectively. Bacteria in blood were lower at 48 h in groups B and D compared with A and in groups F and G compared with E. Total antioxidant status decreased steadily over time in groups A, C, D, and G, but not in groups B and F. TNF-alpha of groups B, C, and D was lower than A at 48 h. Tissue bacteria decreased in group F compared with E. Oleuropein prolonged survival in experimental sepsis probably by promoting phagocytosis or inhibiting biosynthesis of proinflammatory cytokines.     

Abdominal compressions do not achieve similar survival rates compared with chest compressions: an experimental study

Aim

The aim of this study is to investigate whether abdominal compression cardiopulmonary resuscitation (CPR) would result in similar survival rates and neurologic outcome than chest compression CPR in a swine model of cardiac arrest.

Materials and methods

Forty Landrace/Large White piglets were randomized into 2 groups: group A (n = 20) was resuscitated using chest compression CPR, and group B (n = 20) was resuscitated with abdominal compression CPR. Ventricular fibrillation was induced with a pacemaker catheter, and animals were left untreated for 8 minutes. Abdominal and chest compressions were applied with a mechanical compressor. Defibrillation was then attempted.

Results

Neuron-specific enolase and S-100 levels were significantly higher in group B. Ten animals survived for 24 hours in group A in contrast to only 3 animals in group B (P < .05). Neurologic alertness score was worse in group B compared with group A.

Conclusion

Abdominal compression CPR does not improve survival and neurologic outcome in this swine model of cardiac arrest and CPR.