A comparison of the adrenocortical response during septic shock and after complete recovery

Objective To compare the adrenocortical response to corticotropin during septic shock and after complete recovery.Design Prospective clinical study.Setting Multidisciplinary intensive care unit in a university hospital.Patients 20 consecutive patients surviving septic shock. All patients met the American College of Chest Physicians/Society of Critical Care Medicine criteria for septic shock. In addition, the presence of high-output circulatory failure with a cardiac index >41/min per m² was a criterion for enrollment in the study. Complete recovery from septic shock was defined as discontinuation of any supportive therapies. Severity of illness during septic shock and after recovery was graded using the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system.Interventions In each patient, two short corticotropin stimulation tests were done during septic shock and after recovery.Measurements and results Basal cortisol levels recorded during septic shock and after recovery did not differ (medians: 18.8 vs 18.9 g/dl). However, the response to corticotropin was significantly attenuated during septic shock when compared with the response after recovery (medians: 7.7 vs 14.7 g/dl;p=0.02). After recovery, patients' stress response was less, as indicated by a reduction in APACHE II scores (medians: 21 vs 5 points;p<0.01)Conclusions Adrenocortical response to corticotropin is attenuated in patients with septic shock and high-output circulatory failure compared to the response in the much less stressful condition after recovery. The attenuated adrenocortical responsiveness may be explained by effects of circulating mediators from the systemic inflammatory response.     

Plasma volume measurement in septic patients using an albumin dilution technique: comparison with the standard radio-labelled albumin method

Objective To investigate a technique using 20% albumin for measurement of plasma volume in critically ill patients.Design and setting Laboratory and clinical investigation in the adult intensive care unit and anaesthetic laboratories of a university hospital.Patients 12 patients fulfilling ACCP/SCCM criteria for septic shock.Interventions and measurements Each patient received ¹²⁵I-labelled albumin, and the volume of distribution was measured at 1 and 10 min. The accepted standard plasma volume measurement (98% of the 10-min volume of distribution) was calculated. Immediately thereafter 200 ml 20% human albumin was given. Albumin concentrations were measured before and 1 min after this 40-g bolus, and the volume of distribution calculated using a formula that corrected for the 200 ml fluid in which the albumin was dissolved.Results Plasma volumes measured using the albumin dilution technique at 1 min were smaller than the standard technique by 110±280 ml; limits of agreement were from –660 to +440 ml (–16% to +11%). Plasma volumes measured by ¹²⁵I-albumin at 1 min were smaller than the standard by 120±110 ml; limits of agreement were from –330 to +100 ml (–8 to +2%).Conclusions Non-labelled albumin can be used easily and quickly to measure a plasma volume in ICU patients and gives a moderately accurate estimate when compared with the ¹²⁵I-labelled albumin methods. The normal isotope method over-estimates plasma volumes in septic patients because excessive transcapillary escape of albumin is inadequately compensated for by the standard correction factor.Electronic Supplementary Material Electronic supplementary material to this paper can be obtained by using the Springer Link server located at .Dr. Margarsons research post (SIMS Fellow, Magill Department of Anaesthesia) was funded by Smiths Industries Medical Systems     

Mass transfer, clearance and plasma concentration of procalcitonin during continuous venovenous hemofiltration in patients with septic shock and acute oliguric renal failure

Objectives

To measure the mass transfer and clearance of procalcitonin (PCT) in patients with septic shock during continuous venovenous hemofiltration (CVVH), and to assess the mechanisms of elimination of PCT.

Setting

The medical department of intensive care.

Design

A prospective, observational study.

Patients

Thirteen critically ill patients with septic shock and oliguric acute renal failure requiring continuous venovenous postdilution hemofiltration with a high-flux membrane (AN69 or polyamide) and a 'conventional' substitution volume (< 2.5 l/hour).

Measurements and main results

PCT was measured with the Lumitest PCT Brahms^® in the prefilter and postfilter plasma, in the ultrafiltrate at the beginning of CVVH (T0) and 15 min (T15'), 60 min (T60') and 6 hours (T6h) after setup of CVVH, and in the prefilter every 24 hours during 4 days. Mass transfer was determined and the clearance and the sieving coefficient were calculated according to the mass conservation principle. Plasma and ultrafiltrate clearances, respectively, at T15', T60' and T6h were 37 ± 8.6 ml/min (not significant) and 1.8 ± 1.7 ml/min (P < 0.01), 34.7 ± 4.1 ml/min (not significant) and 2.3 ± 1.8 ml/min (P < 0.01), and 31.5 ± 7 ml/min (not significant) and 5 ± 2.3 ml/min (P < 0.01). The sieving coefficient significantly increased from 0.07 at T15' to 0.19 at T6h, with no difference according to the nature of the membrane. PCT plasma levels were not significantly modified during the course of CCVH.

Conclusions

We conclude that PCT is removed from the plasma of patients with septic shock during CCVH. Most of the mass is eliminated by convective flow, but adsorption also contributes to elimination during the first hours of CVVH. The effect of PCT removal with a conventional CVVH substitution fluid rate (<2.5 l/hour) on PCT plasma concentration seems to be limited, and PCT remains a useful diagnostic marker in these septic patients. The impact of high-volume hemofiltration on the PCT clearance, the mass transfer and the plasma concentration should be evaluated in further studies.     

Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials

Introduction

The aim of this study was to examine whether albumin reduced mortality when employed for the resuscitation of adult patients with severe sepsis and septic shock compared with crystalloid by meta-analysis.

Methods

We searched for and gathered data from MEDLINE, Elsevier, Cochrane Central Register of Controlled Trials and Web of Science databases. Studies were eligible if they compared the effects of albumin versus crystalloid therapy on mortality in adult patients with severe sepsis and septic shock. Two reviewers extracted data independently. Disagreements were resolved by discussion with other two reviewers until a consensus was achieved. Data including mortality, sample size of the patients with severe sepsis, sample size of the patients with septic shock and resuscitation endpoints were extracted. Data were analyzed by the methods recommended by the Cochrane Collaboration Review Manager 4.2 software.

Results

A total of 5,534 records were identified through the initial search. Five studies compared albumin with crystalloid. In total, 3,658 severe sepsis and 2,180 septic shock patients were included in the meta-analysis. The heterogeneity was determined to be non-significant (P = 0.86, I² = 0%). Compared with crystalloid, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin (odds ratio (OR) 0.88; 95% CI, 0.76 to 1.01; P = 0.08). However, the use of albumin for resuscitation significantly decreased 90-day mortality in septic shock patients (OR 0.81; 95% CI, 0.67 to 0.97; P = 0.03). Compared with saline, the use of albumin for resuscitation slightly improved outcome in severe sepsis patients (OR 0.81; 95% CI, 0.64 to 1.08; P = 0.09).

Conclusions

In this meta-analysis, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin compared with crystalloid and saline. Moreover, the 90-day mortality of patients with septic shock decreased significantly.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0702-y) contains supplementary material, which is available to authorized users.     

Response of tumour necrosis factor-alpha to delayed in vitro monocyte stimulation in patients with septic shock is related to outcome

We hypothesized that cytokine production following delayed in vitro cell stimulation (to reproduce physiological cellular status at baseline) may be related to outcome in patients with septic shock. A total of 20 patients were included in a prospective clinical study, conducted in a medico-surgical intensive care unit in a university hospital. Blood samples were obtained at the onset of septic shock; these were treated to retain the cells, but to wash out autologous plasma (containing potential inflammatory stimuli such as cytokines, bacterial products and drugs) and replace it with foetal calf serum. Each treated sample was divided into two sets of four aliquots, to be stimulated either immediately or after an overnight period of resting incubation at 37 degrees C. The rest period was to allow recovery from potentially reversible endogenous or pharmacologically induced alterations in cellular response, in order to reproduce a near physiological state at baseline. In vitro cellular challenges used low-dose (0.2 ng/ml) or high-dose (1 ng/ml) CD14-dependent lipopolysaccharide and CD14-independent pokeweed mitogen to induce the production of tumour necrosis factor-alpha (TNF-alpha), and interleukins-1 beta and -10. Levels of TNF-alpha, interleukin-1 beta and interleukin-10 were significantly higher (P<0.05) when cell stimulation was delayed for 16 h, indicating a functional down-regulation of cells during septic shock. Moreover, TNF-alpha responses obtained with high-dose lipopolysaccharide were significantly greater in cells from patients who subsequently survived septic shock (n=13; median value 1392 pg/ml; range 592-2048 pg/ml) than in cells from non-survivors (n=7; median value 708 pg/ml; range 520-1344 pg/ml). These observations support the existence of individual differences in the inflammatory response that could influence patient outcome following septic shock.     

Effects of asphyxia on lung fluid balance in baby lambs.

The purpose of this study was to assess the effects of combined hypoxia and hypercapnia and of severe asphyxia on lung water balance and protein transport in newborn lambs. We studied ten 2-4-wk-old anesthetized lambs which were mechanically ventilated first with air for 2-3 h, then with 10-12% oxygen in nitrogen for 2-4 h, and then with 10-12% oxygen and 10-12% carbon dioxide in nitrogen for 2-4 h. Next we stopped their breathing for 1-2 min to produce severe asphyxia, after which we followed their recovery in air for 2-4 h. In 5 of the 10 lambs we intravenously injected radioactive albumin and measured its turnover time between plasma and lymph during the baseline period and after recovery from asphyxia. During alveolar hypoxia alone, mean pulmonary arterial pressure increased 60% and lung lymph flow increased 74%, whereas lymph protein concentration decreased from 3.47 +/- 0.13 to 2.83 +/- 0.15 g/dl. Cardiac output, left atrial pressure, and plasma protein concentration did not change. When carbon dioxide was added to the inspired gas mixture, pulmonary arterial pressure increased 22%, cardiac output increased 13%, lung lymph flow increased 33%, and lymph protein concentration decreased from 2.83 +/- 0.15 to 2.41 +/- 0.13 g/dl. Left atrial pressure and plasma protein concentration did not change. After 60-90 s of induced asphyxia, vascular pressures and lung lymph flow rapidly returned to values the same as those obtained during the baseline period. The turnover time for radioactive albumin between plasma and lymph was the same between the baseline and recovery periods (185 +/- 16 vs. 179 +/- 12 min). The ratio of albumin to globulin in lymph relative to the same ratio in plasma did not change during any phase of these experiments. Five lambs killed after recovery from asphyxia had significantly less blood and extravascular water in their lungs than control lambs had. We conclude that in the newborn lamb both alveolar hypoxia and alveolar hypoxia with hypercapnia increase lung lymph flow by increasing filtration pressure in the microcirculation, but neither hypoxia with hypercapnia nor brief severe asphyxia alters the protein permeability of the pulmonary microcirculation.     

Defining metabolic acidosis in patients with septic shock using Stewart approach

Purpose

The aim of this study was to define the nature of metabolic acidosis in patients with septic shock on admission to intensive care unit (ICU) using Stewart method. We also aimed to compare the ability of standard base excess (SBE), anion gap (AG), and corrected AG for albumin and lactate (AGcorr) to accurately predict the presence of unmeasured anions (UA).

Patients and Methods

Thirty consecutive patients with septic shock were prospectively included on ICU admission. Stewart equations modified by Figge were used to calculate the strong ion difference and the strong ion gap (SIG).

Results

Most patients had multiple underlying mechanisms explaining the metabolic acidosis. Unmeasured anions and hyperchloremia were present in 70% of the patients. Increased UA were present in 23% of patients with normal values of SBE and [HCO₃⁻]. In these patients, plasma [Cl⁻] was significantly lower compared with patients with low SBE and increased UA (103 [102-106.6] vs 108 [106-111] mmol/L; P = .01, respectively). Corrected AG for albumin and lactate had the best correlation with SIG (r² = 0.94; P < .0001) with good agreement (bias, 0, and precision, 1.22) and highest area under the receiver operating characteristic curve (0.995; 95% confidence interval, 0.87-1) to discriminate SIG acidosis.

Conclusions

Patients with septic shock exhibit a complex metabolic acidosis at ICU admission. High UA may be present with normal values of SBE and [HCO₃⁻] as a result of associated “relative” hypochloremic alkalosis. Corrected AG for albumin and lactate offers the most accurate bedside alternative to Stewart calculation of UA.     

Prognostic values of serum cytokines in septic shock

Objective

To prospectively evaluate the prognostic values of two serum cytokine levels, TNFα and IL 6 serially measured at predetermined intervals in septic shock patients unresponsive to correction of hypoxaemia and plasma volume expansion and treated according to a strict protocol designed to meet specific therapeutic goals (goal-directed therapy). The evolution of serum lactate levels and oxygen-derived parameters was also investigated.

Design

A prospective case series study. Patients were followed-up until they were discharged from the hospital, or died.

Setting

ICU of a university hospital.

Patients

30 consecutive patients with septic shock of various origins.

Interventions

The therapy was aimed at achieving and maintaining for at least 24 h supranormal values CI (≥4.01·min^?1·m^?2), oxygen delivery (DO₂≥550ml· min^?1·m^?2) and oxygen uptake (VO₂≥150ml·min^?1· m^?2) using a combination of fluid loading, norepinephrine, dobutamine and dopamine. A significant decrease in TNFα levels was associated with a favourable outcome while TNFα levels remained elevated in the patients who died in shock or of multiple organ failure. No prognostic value was associated with changes in IL 6 concentrations. In a stepwise logistic regression analysis, only TNFα levels contributed significantly to prediction of patients' outcome. A significant decrease in serum lactate concentrations was observed both in survivors and in patients who survived the episode of septic shock, but subsequently died of multiple organ failure. A positive DO₂/VO₂ relationship was observed only in survivors but did not contribute significantly to prediction of patient outcome.

Conclusions

TNFα is a major mediator involved in the pathogenesis of septic shock and its decrease was significantly associated with a favourable outcome. IL 6 is certainly involved in the pathophysiology of septic shock but further studies are required to determine whether or not it is directly involved in the mediation of late and lethal complications of septic shock. Serum lactate levels and oxygen-derived variables were of less interest as prognostic factors.     

Effects of dobutamine on systemic, regional and microcirculatory perfusion parameters in septic shock: a randomized, placebo-controlled, double-blind, crossover study

Purpose

The role of dobutamine during septic shock resuscitation is still controversial since most clinical studies have been uncontrolled and no physiological study has unequivocally demonstrated a beneficial effect on tissue perfusion. Our objective was to determine the potential benefits of dobutamine on hemodynamic, metabolic, peripheral, hepatosplanchnic and microcirculatory perfusion parameters during early septic shock resuscitation.

Methods

We designed a randomized, controlled, double-blind, crossover study comparing the effects of 2.5-h infusion of dobutamine (5 mcg/kg/min fixed-dose) or placebo in 20 septic shock patients with cardiac index ≥2.5 l/min/m² and hyperlactatemia. Primary outcome was sublingual perfused microvascular density.

Results

Despite an increasing cardiac index, heart rate and left ventricular ejection fraction, dobutamine had no effect on sublingual perfused vessel density [9.0 (7.9–10.1) vs. 9.1 n/mm (7.9–9.9); p = 0.24] or microvascular flow index [2.1 (1.8–2.5) vs. 2.1 (1.9–2.5); p = 0.73] compared to placebo. No differences between dobutamine and placebo were found for the lactate levels, mixed venous-arterial pCO₂ gradient, thenar muscle oxygen saturation, capillary refill time or gastric-to-arterial pCO₂ gradient. The indocyanine green plasma disappearance rate [14.4 (9.5–25.6) vs. 18.8 %/min (11.7–24.6); p = 0.03] and the recovery slope of thenar muscle oxygen saturation after a vascular occlusion test [2.1 (1.1–3.1) vs. 2.5 %/s (1.2–3.4); p = 0.01] were worse with dobutamine compared to placebo.

Conclusions

Dobutamine failed to improve sublingual microcirculatory, metabolic, hepatosplanchnic or peripheral perfusion parameters despite inducing a significant increase in systemic hemodynamic variables in septic shock patients without low cardiac output but with persistent hypoperfusion.     

Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury

Purpose

To study the impact of inflammation/sepsis on the concentrations of neutrophil gelatinase-associated lipocalin (NGAL) in plasma and urine in adult intensive care unit (ICU) patients and to estimate the predictive properties of NGAL in plasma and urine for early detection of acute kidney injury (AKI) in patients with septic shock.

Methods

Sixty-five patients admitted to the general ICU at the Karolinska University Hospital Solna, Sweden, with normal plasma creatinine were assessed for eligibility. Twenty-seven patients with systemic inflammatory response syndrome (SIRS), severe sepsis, or septic shock without AKI and 18 patients with septic shock and concomitant AKI were included in the final analysis. Plasma and urine were analyzed twice daily for plasma NGAL (pNGAL), C-reactive protein (CRP), procalcitonin, myeloperoxidase, plasma cystatin C, plasma creatinine, urine NGAL (uNGAL), urine cystatin C, and urine α1-microglobulin.

Results

Of the 45 patients, 40 had elevated peak levels of pNGAL. Peak levels of pNGAL were not significantly different between septic shock patients with and without AKI. Peak levels of uNGAL were below the upper reference limit in all but four patients without AKI. uNGAL was a good predictor (area under ROC 0.86) whereas pNGAL was a poor predictor (area under ROC 0.67) for AKI within the next 12 h in patients with septic shock.

Conclusions

pNGAL is raised in patients with SIRS, severe sepsis, and septic shock and should be used with caution as a marker of AKI in ICU patients with septic shock. uNGAL is more useful in predicting AKI as the levels are not elevated in septic patients without AKI.     

Septic shock and chemotherapy-induced cytopenia: effects on microcirculation

Purpose

Neutrophil and platelet activation and their interactions with endothelial cells are considered central features of sepsis-induced microcirculatory alterations. However, no study has evaluated the microvascular pattern of septic shock patients with chemotherapy-induced severe cytopenia.

Methods

Demographic and hemodynamic variables together with sublingual microcirculation recording [orthogonal polarization spectral imaging enhanced by sidestream dark-field technology (OPS-SDF) videomicroscopy] were collected in four groups of subjects: septic shock (SS, N?=?9), septic shock in cytopenic patients (NSS, N?=?8), cytopenia without infection (NEUTR, N?=?7), and healthy controls (CTRL, N?=?13). Except for controls, all measurements were repeated after complete resolution of septic shock and/or neutropenia. Video files were processed using appropriate software tool and semiquantitatively evaluated [total vascular density (TVD, mm/mm²), perfused vessel density (PVD, mm/mm²), proportion of perfused vessels (PPV, %), mean flow index (MFI), and flow heterogeneity index (FHI)].

Results

Compared with controls, there were statistically significant microcirculatory alterations within all tested groups of patients (TVD: SS?=?8.8, NSS?=?8.8, NEUTR?=?9.1 versus CTRL?=?12.6, p?p?p?p?p?Conclusions Microvascular derangements in septic shock did not differ between noncytopenic and cytopenic patients. Our data might suggest that profound neutropenia and thrombocytopenia do not render microcirculation more resistant to sepsis-induced microvascular alterations. The role and mechanisms of microvascular alterations associated with chemotherapy-induced cytopenia warrant further investigation.     

Phosphodiesterase 4 inhibition but not beta-adrenergic stimulation suppresses tumor necrosis factor-alpha release in peripheral blood mononuclear cells in septic shock

Introduction

Stimulation of beta₂-adrenergic receptors (β₂-ARs) inhibits tumor necrosis factor-alpha (TNF-α) release in monocytes. In septic shock, endogenous catecholamines induce β₂-AR downregulation, leading to an increased TNF-α release. The aims of this study were to analyze the molecular mechanisms of β-adrenergic downregulation and to explore therapeutic interventions with maintained anti-inflammatory efficacy in septic shock using the inhibition of phosphodiesterase 4 (PDE4).

Methods

We conducted in vitro stimulation of peripheral blood mononuclear cells of healthy volunteers (n = 20) and patients with septic shock (n = 20) with lipopolysaccharide (LPS) or Staphylococcus aureus enterotoxin B (SEB) without or with isoprenaline, forskolin (an activator of adenylate cyclase), or ropipram (an inhibitor of PDE4). We also conducted flow cytometric analysis of Toll-like receptor (TLR) 4 and TLR2 surface expression and intracellular TNF-α production of untreated and stimulated CD14⁺ monocytes. Protein expression of β-ARs, of G proteins, of adenylate cyclase, and of TLRs was measured by Western blotting.

Results

Investigations were done by LPS (100 ng/mL) or SEB (10 ng/mL) when TLR4 and TLR2 were maximally expressed. LPS- or SEB-treated CD14⁺ monocytes of healthy volunteers were able to produce TNF-α. This effect was attenuated by isoprenaline, forskolin, or rolipram in a concentration-dependent manner. In CD14⁺ monocytes of patients with septic shock, the anti-inflammatory effect of isoprenaline was completely blunted whereas efficacy of forskolin and rolipram was maintained. CD14⁺ monocytes of healthy volunteers were compared with patients with septic shock: protein expression of β₂-ARs was reduced and inhibitory G protein was increased, whereas no changes in adenylate cyclase and stimulatory G protein were found.

Conclusions

In septic shock, the anti-inflammatory effects of catecholamines are blunted by downregulation of β₂-ARs and upregulation of the inhibitory G protein in CD14⁺ monocytes. Beta-adrenergic downregulation is overcome by inhibitors of PDE4. These results provide a mechanistic rationale for the therapeutic use of selective PDE4 inhibitors in the treatment of septic shock.     

Evolution of haemodynamics and outcome of fluid-refractory septic shock in children

Background

Maintaining threshold values of cardiac output (CO) and systemic vascular resistance (SVR) when used as part of the American College of Critical Care Medicine (ACCM) haemodynamic protocol improves the outcomes in paediatric septic shock.

Objective

We observed the evolution of CO and SVR during the intensive care admission of children with fluid-refractory septic shock and report this together with the eventual outcomes.

Design

Prospective observational study.

Setting

Tertiary care Paediatric Intensive Care Unit (PICU) in London.

Methods

Children admitted in fluid refractory septic shock to the Intensive Care Unit over a period of 36 months were studied. Post liver re-transplant children and delayed septic shock admissions were excluded. A non-invasive ultrasound cardiac output monitor device (USCOM) was used to measure serial haemodynamics. Children were allocated at presentation into one of two categories: (1) hospital-acquired infection and (2) community-acquired infection. Vasopressor, inotrope or inodilator therapies were titrated to maintain threshold cardiovascular parameters as per the ACCM guidelines.

Results

Thirty-six children [19 male, mean age (SD) 6.78 (5.86) years] were admitted with fluid-refractory septic shock and studied. At presentation, all 18 children with hospital-acquired (HA) sepsis and 3 from among the community-acquired (CA) sepsis group were in ‘warm shock’ (SVRI < 800 dyne s/cm⁵/m²) whereas 15 of the 18 children with community-acquired sepsis and none in the hospital-acquired group were in ‘cold shock’ [cardiac index (CI) < 3.3 l/min/m²]. All 21 children in ‘warm shock’ were initially commenced on a vasopressor (noradrenaline). Despite an initial good response, four patients developed low CI and needed adrenaline. Similarly, all 15 children in cold shock were initially commenced on adrenaline. However, two of them subsequently required noradrenaline. Five others needed milrinone as an inodilator. In general, both groups of children had normalised SVRI and CI within 42 h of therapy but required variable doses of vasopressors, inotropes or inodilators in a heterogeneous manner. The overall 28-day survival rate was 88.9 % in both groups. Central venous oxygen saturation (ScvO2) was significantly (p = 0.003) lower in the community-acquired group (mean 51.72 % ± 4.26) when compared to the hospital-acquired group (mean 58.72 % ± 1.36) at presentation but showed steady improvement during therapy. Gram-positive organisms were predominant in blood cultures, 61 % in HA and 56 % in CA groups.

Conclusions

In general, we found children with community-acquired septic shock presented in cold shock whereas hospital-acquired septic shock children manifested warm shock. Both types evolved in a heterogeneous manner needing frequent revision of cardiovascular support therapy. However the 28-day survival in both groups was the same at 89 %. Frequent measurements of haemodynamics using non-invasive ultrasound helped in fine tuning cardiovascular therapies.     

Hemodynamics and metabolic studies on septic shock in patients with acute liver failure

Backgrounds

Acute liver failure is often accompanied by hyperdynamic circulation, which is also a characteristic of septic shock. Pre-existing acute liver failure may worsen the hemodynamic impairment and prognosis in sepsis.

Aims

To evaluate the hemodynamic and metabolic characteristics and clinical outcomes of septic shock in patients with acute liver failure.

Methods

Twenty patients with acute liver failure and 19 patients without preexisting liver disease were evaluated. Systemic hemodynamics, arterial and mixed vein blood gases, arterial lactate levels, plasma renin activity, and plasma aldosterone levels were checked during the early phase of septic shock.

Results

In acute liver failure group, cardiac index (4.92 ± 1.13 vs 3.69 ± 1.06 L/min per square meter, P < .001) and oxygen delivery (604.7 ± 139.7 vs 485.4 ± 137.3 mL/min per square meter, P = .011) were significantly higher than those without preexisting liver diseases, while systemic vascular resistance index (1041.2 ± 503.3 vs 1409 ± 505.25 dyne·s/cm⁵·m²), oxygen consumption (119.1 ± 29.2 vs 162.4 ± 49.4 mL/min per square meter) and oxygen extraction ratio (20% ± 6% vs. 32% ± 8%) were significantly higher in the latter group. Furthermore, the patients with acute liver failure had higher arterial lactate (P = .026), plasma renin activity (P = .03), plasma aldosterone levels (P < .001), and intensive care unit as well as hospital mortality rates (P = .005, and 0.02 respectively).

Conclusions

In patients with acute liver failure, septic shock was characterized by an accentuated hyperdynamic circulation, hyperlactatemia and an augmented renin-angiotensin-aldosterone system activity. Pre-existing liver failure has a significant impact on the disease severity of septic shock and portends a grave prognosis.     

Changes in plasma calcium during septic shock.

Previous studies have documented a decrease in plasma calcium occurring early after trauma, haemorrhage and cardiac arrest. Therefore, changes in plasma calcium in an ovine experimental model of septic shock due to intraperitoneal sepsis were investigated. Subjects were volume-loaded with Ringer's lactate solution. Plasma calcium and albumin were measured before and 24 h after surgical induction of sepsis. Subjects were divided into two groups according to the severity of shock. Group 1 (n = 8) developed severe hyperdynamic sepsis with renal failure. Group 2 (n = 8) showed no change in blood pressure, cardiac output or renal function. Plasma calcium fell significantly in both groups, and was lower in Group 1 during sepsis (Group 1: 2.36 +/- 0.19 to 1.84 +/- 0.14 mmol l-1; Group 2: 2.34 +/- 0.12 to 2.01 +/- 0.13 mmol l-1; mean +/- SD; both P < 0.001). Plasma albumin fell during sepsis, and the reduction was greater in Group 1. The plasma calcium, corrected for albumin, was still significantly reduced and was similar in each group during sepsis (Group 1: 2.55 +/- 0.13 to 2.23 +/- 0.12 mmol l-1; Group 2: 2.50 +/- 0.08 to 2.27 +/- 0.09 mmol l-1; both P < 0.001). In this large animal model of septic shock, which reproduces the important features of clinical sepsis, there were significant decrements in uncorrected and corrected plasma calcium 24 h after the surgical induction of intraperitoneal sepsis. These changes may contribute to the pathophysiology of this condition.     

Procalcitonin as a diagnostic marker for sepsis/septic shock in the emergency department; a study based on Sepsis-3 definition

Introduction

The recent definition of sepsis was modified based on a scoring system focused on organ failure (Sepsis-3). It would be a time-consuming process to detect the sepsis patient using Sepsis-3. Procalcitonin (PCT) is a well-known biomarker for diagnosing sepsis/septic shock and monitoring the efficacy of treatment. We conducted a study to verify the predictability of PCT for diagnosing sepsis based on Sepsis-3 definition.

Evolution of peripheral vs metabolic perfusion parameters during septic shock resuscitation. A clinical-physiologic study

Purpose

Perfusion assessment during septic shock resuscitation is difficult and usually complex determinations. Capillary refill time (CRT) and central-to-toe temperature difference (Tc-toe) have been proposed as objective reproducible parameters to evaluate peripheral perfusion. The comparative evolution of peripheral vs metabolic perfusion parameters in septic shock resuscitation has not been studied. We conducted a prospective observational clinical-physiologic study to address this subject.

Methods

Patients with sepsis-related circulatory dysfunction were resuscitated according to a standard local algorithm. Perfusion assessment included serial determinations of metabolic (central venous O₂ saturation [Scvo₂] and central venous to arterial Pco₂ gradient [P(cv-a)co₂]) and peripheral perfusion parameters (CRT and Tc-toe, among others). Successful resuscitation was defined as a normal plasma lactate at 24 hours.

Results

Forty-one patients were included. The presence of normal values for both CRT and Tc-toe considered together at 6 hours was independently associated with a successful resuscitation (P = .02), as compared with the behavior of metabolic parameters. Capillary refill time was the first parameter to be significantly normalized.

Conclusion

Early recovery of peripheral perfusion anticipates a successful resuscitation compared with traditional metabolic parameters in septic shock patients. Our findings support the inclusion of serial peripheral perfusion assessment in multimodal monitoring strategies for septic shock resuscitation.     

A Cost-effectiveness Analysis of Albumin in Septic Shock: A Patient-level Data Analysis

PurposeAlbumin-based fluid therapy in septic shock is a matter of debate and criticism. The aim of this study was to assess the cost-effectiveness of albumin therapy in patients with septic shock.MethodsA retrospective cohort study was conducted in Imam Khomeini, Sina, and Shariati hospitals on patients with septic shock admitted to intensive care units from March 31, 2016 to September 22, 2017. Data sources were the health information system database and patient medical records. The patients with potential septic shock were identified based on norepinephrine use. Septic shock was confirmed after medical record review based on systemic inflammatory response syndrome criteria, antibiotic use, and fluid therapy. Patients who received albumin in the fluid therapy were compared with patients treated without albumin. The 28-day mortality, life-year gain, and cost-effectiveness were evaluated.FindingsThe addition of albumin had no significant increase in life-year gain (mean difference = 0.67; 95% CI, −2.25 to 3.58). However, the addition of albumin increased the total cost of treatment by US $3846.07 (95% CI, US $2093.46–US $5598.98). The incremental cost-effectiveness ratio calculated based on the mean life-years gained was US$5740.40 per a life-year gained. The net monetary benefit was negative (−355.4; 95% CI, −15,387.61 to 14,676.81), and the probability that the addition of albumin will be cost-effective at a gross domestic product per capita was 40.0%.ImplicationsAlbumin-based fluid therapy does not improve the 28-day mortality of patients with septic shock. The addition of albumin in the fluid therapy of patients with septic shock was not cost-effective. Both the observational and retrospective nature of the study was expected to introduce bias. We recommend a cost-effectiveness analysis combined with clinical trials to settle the debate once and for all.     

Ventriculoarterial decoupling in human septic shock

Introduction

Septic shock is the most severe manifestation of sepsis. It is characterized as a hypotensive cardiovascular state associated with multiorgan dysfunction and metabolic disturbances. Management of septic shock is targeted at preserving adequate organ perfusion pressure without precipitating pulmonary edema or massive volume overload. Cardiac dysfunction often occurs in septic shock patients and can significantly affect outcomes. One physiologic approach to detect the interaction between the heart and the circulation when both are affected is to examine ventriculoarterial coupling, which is defined by the ratio of arterial elastance (Ea) to left ventricular end-systolic elastance (Ees). In this study, we analyzed ventriculoarterial coupling in a cohort of patients admitted to ICUs who presented with vs without septic shock.

Methods

In this retrospective cross-sectional opportunity study, we measured routine hemodynamics using indwelling arterial and pulmonary arterial catheters and transthoracic echocardiograms in 25 septic patients (group S) and 25 non–septic shock patients (group C) upon ICU admission. Ees was measured by echocardiography using a single-beat (Ees_SB) method. Ea was calculated as 0.9 systolic arterial pressure/stroke volume, and then the Ea/Ees_SB ratio was calculated (normal value <1.36).

Results

In group S, 21 patients had an Ea/Ees_SB ratio >1.36 (uncoupled). The four patients with Ea/Ees_SB ratios ≤1.36 had higher Ees_SB values than patients with Ea/Ees_SB ratios >1.36 (P = 0.007), although Ea measurements were similar in both groups (P = 0.4). In group C, five patients had uncoupled Ea/Ees_SB ratios. No correlation was found between Ees_SB and left ventricular ejection fraction and between Ea/Ees_SB ratio and mixed venous oxygen saturation in septic shock patients.

Conclusions

Upon admission to the ICU, patients in septic shock often display significant ventriculoarterial decoupling that is associated with impaired left ventricular performance. Because Ea/Ees decoupling alters cardiovascular efficiency and cardiac energetic requirements independently of Ea or Ees, we speculate that septic patients with ventriculoarterial uncoupling may benefit from therapy aimed at normalizing the Ea/Ees ratio.     

Platelet-activating factor and phospholipase A2 in patients with septic shock and trauma

Objective To study blood and bronchoalveolar lavage (BAL) fluid levels of platelet activating factor (PAF-acether) and phospholipase A₂ (PLA₂) in patients with septic shock or following severe trauma.Design Prospective controlled clinical study.Setting An intensive care unit (ICU) of a university hospital.Patients and participants The study comprised 12 patients, 8 with septic shock and 4 with trauma, consecutively admitted to the ICU. Healthy volunteers were used as controls.Measurements and results Blood PAF-acether and plasma PLA₂ levels were measured within 24 h after the patients arrival to the ICU. The Apache II score and outcome were registered. Median values for PAF-acether and PLA₂ in the septic shock patients were 10.5×10^–10 M and 5300 units/ml, respectively, whereas corresponding values in the trauma patients were 1.3×10^–10M and 770 units/ml. Normal healthy individuals had no detectable PAF-acether in the circulating blood (<0.5×10^–10 M), and normal plasma PLA₂ activity was <300 units/ml. Moreover, both PLA₂ and PAF-acether levels correlated well with the severity of the disease as assessed by the Apache II scoring system (p<0.01 for PLA₂ andp<0.05 for PAF-acether). In addition, PAF-acether and PLA₂ were determined in BAL fluid of patients with septic shock (n=5) and trauma (n=3); increased PAF-acether levels were found in four patients with septic shock and one patient with trauma.Conclusion These results demonstrate a significant increase of both PLA₂ and PAF-acether in the circulation of trauma patients, and a further increase in septic shock patients. It is possible that PAF-acether and PLA₂ can be used as markers for the severity of the disease in septic shock and following severe trauma.This work was supported by grant B91-17x-05983-11C from the Swedish Medical Research Council and by a grant from Östergötlands Läns Landsting