Decreased mortality with the use of the pulmonary artery catheter?
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Acute Kidney Injury↗
Biomedical subjects
Daniel De Backer
Publications and source records attributed to Daniel De Backer.
Relative adrenal insufficiency in patients with septic shock: comparison of low-dose and conventional corticotropin tests.
OBJECTIVE: To compare a low-dose (1 microg) corticotropin stimulation test with the more standard (250 microg) test for the diagnosis of relative adrenal insufficiency. DESIGN: Diagnostic study. SETTING: Thirty-one-bed mixed medico-surgical department of intensive care. PATIENTS: Forty-six consecutive patients with septic shock. INTERVENTIONS: Corticotropin stimulation tests (low-dose test, 1 microg, and standard 250-microg test), performed consecutively at an interval >4 hrs. MEASUREMENTS AND MAIN RESULTS: In each test, serum cortisol levels were measured before (T0) and 30 (T30), 60 (T60), and 90 (T90) mins after corticotropin injection. The maximal increase in cortisol (Deltamax) was calculated as the difference between T0 and the highest cortisol value at T30, T60, or T90 and considered as adequate if >9 microg/dL (250 nmol/L). Nonresponders to the low-dose test had a lower survival rate than responders to both tests (27 vs. 47%, p = .06; Kaplan Meier curves). Interestingly, nonresponders to high-dose test received hydrocortisone treatment and had a similar survival to responders. Multivariable logistic regression disclosed that the response to the combined low-dose test and high-dose test was an independent predictor of survival (odds ratio 28.91, 95% confidence interval 1.81-462.70, p = .017), whereas basal or maximal cortisol levels in both tests were not. CONCLUSIONS: The low-dose test identified a subgroup of patients in septic shock with inadequate adrenal reserve who had a worse outcome and would have been missed by the high-dose test. These patients may also benefit from glucocorticoid replacement therapy.
Adrenal Insufficiency↗
How monitoring of the microcirculation may help us at the bedside.
PURPOSE OF REVIEW: Recent technologic developments have allowed the direct visualization of the microcirculation at the bedside. The present review explores how the monitoring of microcirculation can help in clinical practice. RECENT FINDINGS: Using orthogonal polarization spectral (OPS) imaging techniques, various investigators have reported microcirculatory alterations in critically ill patients and especially in patients with severe sepsis and septic shock. These alterations include a decrease in vessel density and an increased proportion of nonperfused or intermittently perfused capillaries. The persistence of these alterations is associated with the development of organ failure and death. Several therapeutic interventions, including vasoactive agents, fluid resuscitation, and activated protein C, can affect the microcirculation. Vasoactive agents have variable effects but vasodilatory agents seem very promising. Unfortunately, although many animal studies have investigated the effects of many of these interventions, human data are limited. SUMMARY: Microcirculation plays an important role in the pathogenesis of shock and organ dysfunction, especially in sepsis. Monitoring microcirculation at the bedside may be used to assess severity of the disease and to predict outcome, but in the absence of sufficient data regarding the effects of therapeutic interventions it cannot yet be used to guide therapy, even though this approach is promising.
Belgium↗
A pilot-controlled study of a polymyxin B-immobilized hemoperfusion cartridge in patients with severe sepsis secondary to intra-abdominal infection.
Endotoxin is an important pathogenic trigger for sepsis. The polymyxin B-immobilized endotoxin removal hemoperfusion cartridge, Toraymyxin (hereafter PMX), has been shown to remove endotoxin in preclinical and open-label clinical studies. In a multicenter, open-label, pilot, randomized, controlled study conducted in the intensive care unit in six academic medical centers in Europe, 36 postsurgical patients with severe sepsis or septic shock secondary to intra-abdominal infection were randomized to PMX treatment of 2 h (n = 17) or standard therapy (n = 19). PMX was well tolerated and showed no significant side effects. There were no statistically significant differences in the change in endotoxin levels from baseline to 6 to 8 h after treatment or to 24 h after treatment between the two groups. There was also no significant difference in the change in interleukin (IL)-6 levels from baseline to 6 to 8 h after treatment or to 24 h after treatment between the two groups. Patients treated with PMX demonstrated significant increases in cardiac index (CI; P = 0.012 and 0.032 at days 1 and 2, respectively), left ventricular stroke work index (LVSWI, P = 0.015 at day 2), and oxygen delivery index (DO2I, P = 0.007 at day 2) compared with the controls. The need for continuous renal replacement therapy (CRRT) after study entry was reduced in the PMX group (P = 0.043). There was no significant difference between the groups in organ dysfunction as assessed by the Sequential Organ Failure Assessment (SOFA) scores from day 0 (baseline) to day 6. Treatment using the PMX cartridge is safe and may improve cardiac and renal dysfunction due to sepsis or septic shock. Further studies are needed to prove this effectiveness.
Adult↗
Rapid alterations in transferrin sialylation during sepsis.
The inflammatory process is associated with alterations in iron metabolism. Transferrin, an acute-phase N-glycosylated glycoprotein, plays an important role in iron transport. Human serum transferrin contains two biantennary glycans, each consisting of 0 to 4 molecules of sialic acid (SA); its SA content is heterogeneous with high concentration of tetrasialotransferrin (4SA) and low amounts of disialo-, trisialo-, penta-, and hexasialotransferrin. The hepatic uptake of iron is greater for desialylated transferrin isoforms (disialotransferrin) than for the other forms. We hypothesized that serum levels of carbohydrate-deficient transferrin (CDT, disialotransferrin) may increase rapidly in septic patients. Blood samples were obtained from critically ill patients with (n = 15) and without (n = 14) documented sepsis and compared with healthy volunteers. The different forms of transferrin were studied by capillary zone electrophoresis; SA concentrations were measured by enzymatic colorimetric assay. There was a significant increase in the proportion of CDT in septic compared with nonseptic patients and volunteers (18.3% [1.3-30.5] vs. 0.7% [0.5-0.9]; P < 0.01 and 0.9% [0.5-1.1]; P < 0.05). Conversely, tri- and tetrasialotransferrin levels were lower in septic patients. Total and free SA concentrations were significantly higher in septic patients than in healthy volunteers. In a sheep model of septic shock secondary to peritonitis, serum free SA was already increased after 15 h. Sepsis is associated with decreased SA content on circulating transferrin and with an increase in blood free SA concentrations. In view of these rapid modifications and the long half-life of transferrin, the most likely explanation is degradation of transferrin by neuraminidase. Further studies including measurement of blood neuraminidase concentration and activity are needed to understand the process and exact role of SA decrease in septic patients.
Acute Disease↗
The following is the abstract of the article discussed in the subsequent letter:.
Sublingual and intestinal mucosal blood flow and Pco(2) were studied in a canine model of endotoxin-induced circulatory shock and resuscitation. Sublingual Pco(2) (Ps(CO(2))) was measured by using a novel fluorescent optrode-based technique and compared with lingual measurements obtained by using a Stowe-Severinghaus electrode [lingual Pco(2) (Pl(CO(2)))]. Endotoxin caused parallel changes in cardiac output, and in portal, intestinal mucosal, and sublingual blood flow (Q(s)). Different blood flow patterns were observed during resuscitation: intestinal mucosal blood flow returned to near baseline levels postfluid resuscitation and decreased by 21% after vasopressor resuscitation, whereas Q(s) rose to twice that of the preshock level and was maintained throughout the resuscitation period. Electrochemical and fluorescent Pco(2) measurements showed similar changes throughout the experiments. The shock-induced increases in Ps(CO(2)) and Pl(CO(2)) were nearly reversed after fluid resuscitation, despite persistent systemic arterial hypotension. Vasopressor administration induced a rebound of Ps(CO(2)) and Pl(CO(2)) to shock levels, despite higher cardiac output and Q(s), possibly due to blood flow redistribution and shunting. Changes in Pl(CO(2)) and Ps(CO(2)) paralleled gastric and intestinal Pco(2) changes during shock but not during resuscitation. We found that the lingual, splanchnic, and systemic circulations follow a similar pattern of blood flow variations in response to endotoxin shock, although discrepancies were observed during resuscitation. Restoration of systemic, splanchnic, and lingual perfusion can be accompanied by persistent tissue hypercarbia, mainly lingual and intestinal, more so when a vasopressor agent is used to normalize systemic hemodynamic variables.
Animals↗
[Comparison of dobutamine under different fluids resuscitation for shock induced by ischemia/reperfusion].
OBJECTIVE: To compare the effects of dobutamine under different fluids resuscitation for shock induced by intestinal ischemia/reperfusion (I/R) injury in rabbits. METHODS: Thirty-two anesthetized rabbits were randomized into four groups of eight animals each. The groups were followed as: (1) lactated Ringer's solution (LRS) resuscitation; (2) LRS+hydroxyethyl starch solution (HES) resuscitation; (3) LRS resuscitation+dobutamine treatment; (4) LRS+HES resuscitation+dobutamine treatment. All these rabbits underwent the intestinal I/R injury developed by occluding superior mesenteric artery (SMA) with a non-crushing vascular clamp for 60 minutes and then loosing the clamp for 300 minutes. The fluid resuscitation and drug treatment began at the same time of reperfusion. Hemodynamic parameters including mean artery pressure (MAP), heart rate (HR), aortic velocity (AoV, as cardiac output) and SMA blood flow (Qsma) were measured. Tissue oxygenation was assessed indirectly by measuring the tonometric parameters of the gut, including difference between partial pressure of carbon dioxide in intestinal intramucosal and partial pressure of carbon dioxide in arterial blood (Pt-a CO2 gap), intestinal intramucosal pH (pHi), arterial blood lactate acid concentration and oxygen delivery (DO2). RESULTS: HR, AoV and Qsma as measured in two dobutamine groups were significantly higher in values than LRS and LRS+HES groups (all P<0.05). But MAP as measured in two dobutamine groups were significantly higher in values than only LRS (P<0.05), and in LRS+HES resuscitation+dobutamine treatment group was also significantly higher in values than LRS resuscitation+dobutamine treatment group (P<0.05). Dobutamine in LRS resuscitation+dobutamine treatment and LRS+HES resuscitation+dobutamine treatment group could greatly decrease lactate and Pt-aCO2 gap, significantly improve pHi and DO2 compared with other two resuscitation groups (all P<0.05). Dobutamine in LRS+HES resuscitation+dobutamine treatment group could also greatly decrease lactate and Pt-aCO2 gap, significantly improve pHi compared with LRS resuscitation+dobutamine treatment group (all P<0.05). CONCLUSION: Dobutamine could improve hemodynamic parameters and tissue oxygenation in shock induced by intestinal I/R injury in rabbits, being better used under the LRS+HES resuscitation.
Animals↗
The cuff-leak test: what are we measuring?
Stridor is one of the most frequent causes of early extubation failure. The cuff-leak test may help to identify patients at risk to develop post-extubation laryngeal edema. However the discrimination power of the cuff-leak test is highly variable and can be use, at best, to detect patients at risk to develop edema but should not be used to postpone extubation as tracheal extubation can still be successful in many patients with a positive test. In this editorial, the author discuss the factors influencing the leak and hence its predictive value.
Equipment Failure↗
Oxygen transport-the oxygen delivery controversy.
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Animals↗
Effects of fluid challenge on gastric mucosal PCO2 in septic patients.
OBJECTIVE: To determine the effects of fluid challenge on systemic hemodynamic variables and gastric intramucosal partial pressure of carbon dioxide (PCO(2)) in septic patients. DESIGN: Short-term interventional study. SETTING: Medical-surgical intensive care unit in a university hospital. PATIENTS: Twenty-four adult patients with severe sepsis or septic shock requiring volume replacement. All patients were studied within 24 h of onset of severe sepsis or septic shock. INTERVENTIONS: Five hundred milliliters of a 6% hydroxyethyl starch (HES) solution were administered in 30 min. MEASUREMENTS AND RESULTS: Complete hemodynamic data, blood samples, and gastric mucosal PCO(2) (automatic gas capnometry) determinations were obtained at baseline and 15 min after the end of fluid infusion. After fluid challenge, cardiac index (CI) increased from 3.8 (range 2.9-4.2) to 4.2 (range 3.1-4.9) l/min m(-2) ( p<0.05). The PCO(2) gap decreased from 9.8 (range 6.9-26.0) to 8.5 (range 6.6-17.4) mm Hg ( p<0.05), but important individual variations were observed. We failed to observe significant relationships between changes in CI and in PCO(2) gap, or between indices of preload (pulmonary artery occluded pressure, right atrial pressure, and pulse pressure variations) and changes in PCO(2) gap. In addition, changes in PCO(2) gap and in (v-a) CO(2) were not related; however, changes in PCO(2) gap were related to baseline PCO(2) gap ( p=0.003), PEEP ( p=0.02), and cumulative doses of vasopressors ( p=0.02). CONCLUSIONS: The effects of fluid challenge on gastric mucosal PCO(2) are variable and related to baseline PCO(2) gap rather than to systemic variables. In general, rapid volume infusion decreases PCO(2) gap, but this effect is more pronounced in patients with presumably impaired mucosal perfusion.
Adult↗
Microvascular alterations in patients with acute severe heart failure and cardiogenic shock.
BACKGROUND: Microvascular blood flow alterations may impair tissue oxygenation and may participate in the development of multiple organ failure in patients with severe heart failure. We hypothesized that microvascular blood flow alterations are present in patients with severe heart failure and cardiogenic shock. METHODS: We used an orthogonal polarization spectral imaging technique to investigate the sublingual microcirculation in 40 patients with acute severe heart failure, including 31 patients with cardiogenic shock, and in a control group of 15 patients who were examined the day before cardiac surgery. The effects of topical application of acetylcholine (10-2M) were also tested in 5 patients with cardiogenic shock. Five sublingual areas were recorded, allocated a random number, and later analyzed semiquantitatively. Data were analyzed with non-parametric tests and presented as medians (percentiles 25-75). RESULTS: The density of all the vessels was similar in the 3 groups. The proportion of perfused small (<20 microm) vessels was lower in patients with cardiac failure and cardiogenic shock than in control patients (63% [46%-65%] and 49% [38%-64%] vs 92% [90%-93%], P <.001). The perfusion of large vessels was preserved in all groups. The proportion of perfused vessels was higher in patients who survived than in patients who did not survive in all vessels (90% [84%-93%] vs 81% [74%-87%], P <.05) and in small vessels (64% [49%-68%] vs 43% [37%-62%], P <.05). The topical application of acetylcholine totally reversed these alterations CONCLUSIONS: Microvascular blood flow alterations are frequently observed in patients with severe heart failure and are more severe in patients who do not survive.
Acetylcholine↗
The hepatosplanchnic contribution to hyperlactatemia in endotoxic shock: effects of tissue ischemia.
We investigated the role of the hepatosplanchnic region in the hyperlactatemia observed during endotoxic shock. The study included 18 dogs anesthetized with pentobarbital and mechanically ventilated. After baseline measurements, including gut lactate production (GLP), liver lactate uptake (LLU), liver lactate extraction (LLE), and hepatosplanchnic lactate production (HSLP), each dog received 2 mg/kg of E. coli endotoxin. After a second set of measurements, cardiac tamponade was induced in 12 dogs (EDTX + Tamp) by repeated injections of normal saline into the pericardial sac to progressively reduce cardiac output and hepatic blood flow. The six remaining dogs served as septic controls (EDTX). From a net lactate consumer before endotoxin infusion, the gut became a lactate producer after the endotoxin infusion, with GLP increasing from -11.4 +/- 27.0 to 32.9 +/- 38.2 x 10(-3) mEq/min (P < 0.05). LLU increased from 48.1 +/- 26.2 to 86.6 +/- 45.2 x 10(-3) mEq/min (P < 0.05), so that LLE and HSLP did not change. In the EDTX + Tamp group, LLE became negative, and HSLP became positive only when hepatic oxygen delivery reached its critical value during cardiac tamponade. In the EDTX group, LLE remained positive and HSLP negative. In endotoxic shock, GLP is increased, but the liver can metabolize this additional load of lactate, so that the hepatosplanchnic area is not a major source of lactate unless the liver becomes profoundly hypoxic.
Animals↗
Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock.
OBJECTIVE: To characterize the time course of microcirculatory alterations and their relation to outcome in patients with septic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one-bed, medico-surgical intensive care unit in a university hospital. PATIENTS: Forty-nine patients with septic shock. INTERVENTIONS: The sublingual microcirculation was investigated with an orthogonal polarization spectral imaging device on the day of onset of septic shock (baseline) and each day until resolution of shock. MEASUREMENTS AND MAIN RESULTS: Five sequences of 20 secs each were recorded and analyzed off-line by a semiquantitative method. Data were analyzed with nonparametric tests and presented as median (25th-75th percentiles). Three patients died after the resolution of shock from unrelated causes and were excluded. Of the other 46 patients, 26 survived and 20 died: 13 due to unresolving shock and seven due to persistent multiple organ failure after resolution of shock. At the onset of shock, survivors and nonsurvivors had similar vascular density (5.6 [4.7-7.0] vs. 6.2 [5.4-7.0]/mL; p = nonsignificant) and percentage of perfused small vessels (65.0 [53.1-68.9] vs. 58.4 [47.5-69.1]%; p = nonsignificant). Small vessel perfusion improved over time in survivors (analysis of variance, p <.05 between survivors and nonsurvivors) but not in nonsurvivors. Despite similar hemodynamic and oxygenation profiles and use of vasopressors at the end of shock, patients dying after the resolution of shock in multiple organ failure had a lower percentage of perfused small vessels than survivors (57.4 [46.6-64.9] vs. 79.3 [67.2-83.2]%; p =.02). CONCLUSIONS: Microcirculatory alterations improve rapidly in septic shock survivors but not in patients dying with multiple organ failure, regardless of whether shock has resolved.
Aged↗
Septic shock of early or late onset: does it matter?
STUDY OBJECTIVES: To determine possible differences in morbidity and mortality between early and late onset of septic shock in ICU patients. DESIGN: Systematic data collection. SETTING: Thirty-one-bed, mixed, medicosurgical ICU in a university hospital. PATIENTS: All 65 patients who acquired septic shock after admission to the ICU between February 1999 and April 2000. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Forty-one of the 65 patients presented with septic shock within 24 h of admission to the ICU (early septic shock [ESS]); the other 21 patients acquired septic shock > 24 h after ICU admission (late septic shock [LSS]). Eleven patients had a second episode (7 patients in the ESS group, and 4 patients in the LSS group), and 1 patient in the LSS group had a third episode of septic shock. Patients with ESS had higher APACHE (acute physiology and chronic health evaluation) II (mean +/- SD, 26 +/- 6 vs 20 +/- 6; p = 0.002) and sequential organ failure assessment (SOFA) scores (11 +/- 3 vs 7 +/- 3, p < 0.001) on ICU admission, and a higher blood lactate concentration at the onset of shock (median 3.70 mEq/L; interquartile range, 2.6 to 6.6 mEq/L; vs median, 2.50 mEq/L [interquartile range, 1.8 to 4.0 mEq/L], p = 0.03) than patients with LSS. However, the duration of septic shock (median, 42 h [interquartile range, 21 to 97 h] vs median, 93 h [interquartile range, 32 to 241 h], p = 0.058) and the length of ICU stay after the onset of septic shock (median, 75 h; [interquartile range, 38 to 203 h] vs median, 321 h [interquartile range, 96 to 438 h], p = 0.018), was shorter in patients with ESS than patients with LSS. The ICU mortality rate was 63% (26 patients) in the ESS group, and 88% (21 patients) in the LSS group (p = 0.071). At the onset of the first episode of shock, patients with ESS had higher SOFA scores (11 +/- 3 vs 9 +/- 3, p = 0.045), lower pH (7.24 +/- 0.15 vs 7.33 +/- 0.12, p = 0.01), and were treated with higher doses of dopamine (median, 20 microg/kg/min [interquartile range, 14 to 20 microg/kg/min] vs median, 12 microg/kg/min [interquartile range, 8 to 20 microg/kg/min], p = 0.028) than patients with LSS. CONCLUSIONS: Septic shock is more severe when of early onset, as reflected by more severe organ dysfunction, greater lactic acidosis, and higher vasopressor requirements, yet the outcome is better, as reflected by a shorter duration of the shock episode, shorter ICU stay, and slightly lower mortality rates. These differences may influence clinical trials of therapeutic agents for sepsis, and should be taken into account when analyzing the results.
APACHE↗
Clinical review: influence of vasoactive and other therapies on intestinal and hepatic circulations in patients with septic shock.
The organs of the hepatosplanchnic system are considered to play a key role in the development of multiorgan failure during septic shock. Impaired oxygenation of the intestinal mucosa can lead to disruption of the intestinal barrier, which may promote a vicious cycle of inflammatory response, increased oxygen demand and inadequate oxygen supply. Standard septic shock therapy includes supportive treatment such as fluid resuscitation, administration of vasopressors (adrenergic and nonadrenergic drugs), and respiratory and renal support. These therapies may have beneficial or detrimental effects not only on systemic haemodynamics but also on splanchnic haemodynamics, at both the macrocirculatory and microcirculatory levels. This clinical review focuses on the splanchnic haemodynamic and metabolic effects of standard therapies used in patients with septic shock, as well as on the recently described nonconventional therapies such as vasopressin, prostacyclin and N-acetyl cysteine.
Acetylcysteine↗
Lactic acidosis: an early marker of propofol infusion syndrome?
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Acidosis, Lactic↗
Arginine vasopressin in advanced vasodilatory shock.
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Arginine Vasopressin↗
Gut mucosal damage during endotoxic shock is due to mechanisms other than gut ischemia.
Whether the gut alterations seen during sepsis are caused by microcirculatory hypoxia or disturbances in cellular metabolic pathways associated with mitochondrial respiration remains controversial. We hypothesized that hypoperfusion or hypoxia and local production of nitric oxide might play an important role in the development of gut mucosal injury during endotoxic shock and investigated their roles by using differing levels of fluid resuscitation and occlusion of the superior mesenteric artery (SMA). Anesthetized New Zealand rabbits were allocated to group I (sham, n = 8); group II [low-dose endotoxin (LPS, Escherichia coli-055:B5, 150 microg/kg)/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 8]; group III [high-dose LPS (1 mg/kg)/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 8]; group IV [high-dose LPS (1 mg/kg)/hypovolemia (4 ml x kg-1 x h(-1) fluids); n = 8]; and group V [SMA ligation/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 4]. Luminal gut lactate concentrations and PCO2 gap increased in groups IV and V (P < 0.05), reflecting alterations in gut perfusion. Interestingly, significant histological alterations were observed in all LPS groups but not in group V. Blood and luminal gut nitrate/nitrite concentrations increased only in group IV. The mechanism of gut injury in endotoxic shock seems unrelated to hypoxia and release of nitric oxide. Gut dysfunction may occur as a result of so-called "cytopathic hypoxia."
Animals↗