Year in review in Intensive Care Medicine, 2006. II. Infections and sepsis, haemodynamics, elderly, invasive and noninvasive mechanical ventilation, weaning, ARDS.
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Aged↗
Biomedical subjects
Daniel De Backer
Publications and source records attributed to Daniel De Backer.
Year in review in Intensive Care Medicine, 2006. I. Experimental studies. Clinical studies: brain injury, renal failure and endocrinology.
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Brain Injuries↗
Sublingual capnometry tracks microcirculatory changes in septic patients.
OBJECTIVE: To test the hypothesis that microcirculatory blood flow is the main determinant of sublingual carbon dioxide pressure in patients with septic shock. DESIGN: Prospective, open-label study. SETTING: A 31-bed medico-surgical department of intensive care. PATIENTS: Eighteen consecutive mechanically ventilated patients with septic shock. INTERVENTIONS: A 5 microg/kg x min dobutamine infusion was used to increase blood flow. METHODS: Sublingual carbon dioxide pressure was monitored using a microelectrode sensor, and sublingual microcirculation was assessed using orthogonal polarization spectral imaging. The sublingual carbon dioxide pressure gap was calculated as the difference between sublingual and arterial carbon dioxide pressures. In each patient, a nasogastric tonometry catheter was inserted for gastric mucosal carbon dioxide pressure measurement. The gastric carbon dioxide pressure gap was calculated as the difference between gastric mucosal and arterial carbon dioxide pressures. MEASUREMENTS AND RESULTS: Dobutamine infusion was associated with increases cardiac index and mixed venous blood oxygen saturation. Dobutamine infusion resulted in decreases in sublingual carbon dioxide pressure gap from 40+/-15 to 17+/-8 mmHg (p<0.01). There was a significant correlation between sublingual and gastric mucosal carbon dioxide pressures (r 2=0.61, p<0.05). At baseline, sublingual carbon dioxide pressure gap correlated with the proportion of well-perfused capillaries (r 2=0.80). The decrease in sublingual carbon dioxide pressure gap paralleled the increase in the proportion of well-perfused capillaries in each patient. CONCLUSIONS: Regional microcirculatory blood flow is the main determinant of sublingual carbon dioxide pressure. Sublingual capnometry could represent a simple, non-invasive method to monitor these microcirculatory alterations in septic patients.
Aged↗
Hemodynamic management of septic shock.
Septic shock is characterized by profound cardiovascular alterations, including hypovolemia, severe alterations in vascular tone, and myocardial depression. These effects can lead to tissue hypoperfusion, the persistence of which could contribute to multiple organ failure. In addition, regional blood flow alterations and microvascular blood flow alterations may coexist and persist even after whole body hemodynamic alterations are corrected. Early aggressive interventions to improve oxygen delivery have been shown to improve outcome, but ongoing hemodynamic support is often required. This review will examine the hemodynamic management of patients with septic shock.
Journal Article↗
The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects.
OBJECTIVE: To evaluate the effects of dobutamine on microcirculatory blood flow alterations in patients with septic shock. DESIGN: Prospective, open-label study. SETTING: A 31-bed, medico-surgical intensive care unit of a university hospital. PATIENTS: Twenty-two patients with septic shock. INTERVENTIONS: Intravenous administration of dobutamine (5 mug/kg.min) for 2 hrs (n = 22) followed by the addition of 10 M acetylcholine (topically applied, n = 10). MEASUREMENTS AND MAIN RESULTS: Complete hemodynamic measurements were obtained before and after dobutamine administration. In addition, the sublingual microcirculation was investigated with an orthogonal polarization spectral imaging technique before and after dobutamine administration and after topical application of acetylcholine. Dobutamine significantly improved capillary perfusion (from 48 +/- 15 to 67 +/- 11%, p = .001), but with large individual variation, whereas capillary density remained stable. The addition of topical acetylcholine completely restored capillary perfusion (98 +/- 1%, p = .001) and capillary density. The changes in capillary perfusion during dobutamine administration were not related to changes in cardiac index (p = .45) or arterial pressure (p = .29). Interestingly, the decrease in lactate levels was proportional to the improvement in capillary perfusion (y = 0.07 - 0.02x, r = .46, p = .005) but not to changes in cardiac index (p = .55). CONCLUSIONS: The administration of 5 mug/kg.min dobutamine can improve but not restore capillary perfusion in patients with septic shock. These changes are independent of changes in systemic hemodynamic variables.
Acetylcholine↗
Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study.
OBJECTIVE: The optimal adrenergic support in shock is controversial. We investigated whether dopamine administration influences the outcome from shock. DESIGN: Cohort, multiple-center, observational study. SETTING: One hundred and ninety-eight European intensive care units. PATIENTS: All adult patients admitted to a participating intensive care unit between May 1 and May 15, 2002. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were followed up until death, until hospital discharge, or for 60 days. Shock was defined as hemodynamic compromise necessitating the administration of vasopressor catecholamines. Of 3,147 patients, 1,058 (33.6%) had shock at any time; 462 (14.7%) had septic shock. The intensive care unit mortality rate for shock was 38.3% and 47.4% for septic shock. Of patients in shock, 375 (35.4%) received dopamine (dopamine group) and 683 (64.6%) never received dopamine. Age, gender, Simplified Acute Physiology Score II, and Sequential Organ Failure Assessment score were comparable between the two groups. The dopamine group had higher intensive care unit (42.9% vs. 35.7%, p=.02) and hospital (49.9% vs. 41.7%, p=.01) mortality rates. A Kaplan-Meier survival curve showed diminished 30 day-survival in the dopamine group (log rank=4.6, p=.032). In a multivariate analysis with intensive care unit outcome as the dependent factor, age, cancer, medical admissions, higher mean Sequential Organ Failure Assessment score, higher mean fluid balance, and dopamine administration were independent risk factors for intensive care unit mortality in patients with shock. CONCLUSIONS: This observational study suggests that dopamine administration may be associated with increased mortality rates in shock. There is a need for a prospective study comparing dopamine with other catecholamines in the management of circulatory shock.
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L-arginine and vasopressor agents: when antagonists have unexpected synergistic effects.
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Animals↗
Effects of drotrecogin alfa activated on microcirculatory alterations in patients with severe sepsis.
OBJECTIVE: Microvascular alterations may play an important role in the development of sepsis-induced organ dysfunction. Drotrecogin alfa activated (DAA) improves outcome in patients with severe sepsis, but its precise mechanism of action is not entirely defined. We investigated whether DAA can influence microcirculatory alterations in patients with severe sepsis. DESIGN: Prospective, nonrandomized study. SETTING: A 31-bed, medico-surgical intensive care unit of a university hospital. PATIENTS: Forty adult patients with severe sepsis who met the EU criteria for DAA administration. INTERVENTIONS: Twenty patients received the drug (DAA) and 20 had a contraindication to DAA administration (control). MEASUREMENTS AND MAIN RESULTS: An orthogonal polarization spectral imaging technique was used to visualize the sublingual microcirculation. In all patients, measurements were obtained at baseline, 4 hrs later, and then every 24 hrs for up to 7 days. In patients receiving DAA, measurements were also obtained just before and 4 hrs after the end of DAA infusion. The two groups were well matched for severity of disease, number of failing organs, and the degree of microvascular alterations at baseline. The proportion of perfused capillaries increased in the DAA treated patients already at 4 hrs (from 64% [51-80%] to 84% [71-88%], p < .01) but not in the control group (from 67% [59-76%] to 68% [61-71%], p = not significant). Microvascular perfusion decreased transiently at the end of DAA infusion. The improvement in microvascular blood flow was associated with a more rapid resolution of hyperlactatemia. CONCLUSIONS: DAA administration rapidly improves sepsis-induced microvascular alterations, whereas its cessation is associated with a transient deterioration.
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Albumin administration improves organ function in critically ill hypoalbuminemic patients: A prospective, randomized, controlled, pilot study.
OBJECTIVE: To test the hypothesis that administration of albumin to correct hypoalbuminemia might have beneficial effects on organ function in a mixed population of critically ill patients. DESIGN: : Prospective, controlled, randomized study. SETTING: Thirty-one-bed, mixed medicosurgical department of intensive care. PATIENTS: All adult patients with a serum albumin concentration < or =30 g/L were assessed for eligibility. Principal exclusion criteria were expected length of stay <72 hrs, life expectancy <3 months or a do-not-resuscitate order, albumin administration in the preceding 24 hrs, or evidence of fluid overload. INTERVENTIONS: The 100 patients were randomized to receive 300 mL of 20% albumin solution on the first day, then 200 mL/day provided their serum albumin concentration was <31 g/dL (albumin group), or to receive no albumin (control group). MEASUREMENTS AND MAIN RESULTS: The primary outcome was the effect of albumin administration on organ function as assessed by a delta Sequential Organ Failure Assessment score from day 1 to day 7 (or the day of intensive care discharge or death, whichever came first). The two groups of 50 patients were comparable at baseline for age, gender, albumin concentration, and Acute Physiology and Chronic Health Evaluation II score. Albumin concentration did not change over time in the control group but increased consistently in the albumin group (p < .001). Organ function improved more in the albumin than in the control group (p = .026), mainly due to a difference in respiratory, cardiovascular, and central nervous system components of the Sequential Organ Failure Assessment score. Diuretic use was identical in both groups, but mean fluid gain was almost three times higher in the control group (1679 +/- 1156 vs. 658 +/- 1101 mL, p = .04). Median daily calorie intake was higher in the albumin than in the control group (1122 [935-1158] vs. 760 [571-1077] kcal, p = .05). CONCLUSIONS: Albumin administration may improve organ function in hypoalbuminemic critically ill patients. It results in a less positive fluid balance and a better tolerance to enteral feeding.
Adult↗
Prediction of postoperative complications after urgent laparotomy by intraperitoneal microdialysis: A pilot study.
OBJECTIVE: The aim of the present study was to investigate the role of intraperitoneal microdialysis (IPM) techniques in monitoring the evolution of postoperative critically ill patients requiring urgent laparotomy. SUMMARY BACKGROUND DATA: Postoperative intraabdominal sepsis is associated with an important degree of morbidity and mortality in acutely ill patients. Early diagnosis is critical to improve outcomes. METHODS: : The study included 25 consecutive patients admitted to the intensive care unit (ICU) after urgent laparotomy. Measurements of microdialysate fluid were performed through a microdialysis catheter, positioned intraperitoneally, during the first 5 postoperative days and lactate/pyruvate (L/P) ratios calculated. Patients were followed until hospital discharge. RESULTS: Ten patients had a complicated postoperative course, including 4 deaths (3 refractory shock, 1 mesenteric ischemia), 3 reinterventions (1 necrotic collection, 1 mesenteric ischemia, 1 biliary leak), 2 secondary peritonitis, and 1 intraabdominal collection. The IPM L/P ratio in these patients was already significantly higher during the first 24 postoperative hours compared with patients who had no complications (35 +/- 21 vs. 18 +/- 6, P < 0.01). An IPM L/P ratio above 22 on postoperative day 1 had a sensitivity of 0.64 and a specificity of 0.79 for complications. There were no significant differences between the two groups in pH, lactate, white blood cell count, or subcutaneous L/P ratio. No complication was associated with the technique. CONCLUSIONS: IPM is safe and reliable and provides valuable information after urgent laparotomy. Persistently high L/P values should raise the possibility of serious postoperative complications.
Adult↗
How can the response to volume expansion in patients with spontaneous respiratory movements be predicted?
INTRODUCTION: The aim of the study was to evaluate the ability of different static and dynamic measurements of preload to predict fluid responsiveness in patients with spontaneous respiratory movements. METHODS: The subjects were 21 critically ill patients with spontaneous breathing movements receiving mechanical ventilation with pressure support mode (n = 9) or breathing through a face mask (n = 12), and who required a fluid challenge. Complete hemodynamic measurements, including pulmonary artery occluded pressure (PAOP), right atrial pressure (RAP), pulse pressure variation (DeltaPP) and inspiratory variation in RAP were obtained before and after fluid challenge. Fluid challenge consisted of boluses of either crystalloid or colloid until cardiac output reached a plateau. Receiver operating characteristics (ROC) curve analysis was used to evaluate the predictive value of the indices to the response to fluids, as defined by an increase in cardiac index of 15% or more. RESULTS: Cardiac index increased from 3.0 (2.3 to 3.5) to 3.5 (3.0 to 3.9) l minute-1 m-2 (medians and 25th and 75th centiles), p < 0.05. At baseline, DeltaPP varied between 0% and 49%. There were no significant differences in DeltaPP, PAOP, RAP and inspiratory variation in RAP between fluid responders and non-responders. Fluid responsiveness was predicted better with static indices (ROC curve area +/- SD: 0.73 +/- 0.13 for PAOP, p < 0.05 vs DeltaPP and 0.69 +/- 0.12 for RAP, p = 0.054 compared with DeltaPP) than with dynamic indices of preload (0.40 +/- 0.13 for DeltaPP and 0.53 +/- 0.13 for inspiratory changes in RAP, p not significant compared with DeltaPP). CONCLUSION: In patients with spontaneous respiratory movements, DeltaPP and inspiratory changes in RAP failed to predict the response to volume expansion.
Aged↗
Can passive leg raising be used to guide fluid administration?
Predicting fluid responsiveness has become a topic of major interest. Measurements of intravascular pressures and volumes often fail to predict the response to fluids, even though very low values are usually associated with a positive response to fluids. Dynamic indices reflecting respiratory-induced variations in stroke volume have been developed; however, these cannot be used in patients with arrhythmia or with spontaneous respiratory movements. The passive leg raising (PLR) test has been suggested to predict fluid responsiveness. PLR induces an abrupt increase in preload due to autotransfusion of blood contained in capacitance veins of the legs, which leads to an increase in cardiac output in preload-dependent patients. This commentary discusses some of the technical issues related to this test.
Fluid Therapy↗
Optimal management of the high risk surgical patient: beta stimulation or beta blockade?
Several groups of investigators have shown that peri-operative goal directed therapy (GDT) may reduce mortality in high-risk surgical patients. GDT usually requires the use of beta-adrenergic agents, however, and these may also carry the risk of cardiac ischemia, especially in patients with ischemic diseases. In this commentary, we will discuss the apparent contradiction between studies showing beneficial effects of GDT in high-risk surgical patients and studies showing the benefit of beta-blockade in high-risk surgery. One of the key differences between both types of studies is that GDT is applied in patients with high risk of postoperative death, excluding patients with cardiac ischemic disease, while studies reporting beneficial effects of beta-blockade have investigated patients with high risk of cardiac ischemia but moderate risk of death related to the surgical procedure itself. It is likely that beta-blockade should be proposed in patients with moderate risk of death, whereas GDT using fluids and inotropic agents should be applied in patients with high risk of peri-operative death. Monitoring central venous oxygen saturation may be useful to individualize therapy, but further studies are required to validate this option.
Adrenergic beta-Agonists↗
Pneumonia-induced sepsis and gut injury: effects of a poly-(ADP-ribose) polymerase inhibitor.
BACKGROUND: Pseudomonas aeruginosa is commonly associated with nosocomial pneumonia. Ileal mucosal injury may be induced by severe lung infection. During septic shock, peroxynitrite-mediated DNA strand-breaks activate the enzyme poly-(ADP)-ribose polymerase (PARP) resulting in cellular energetic suppression and cell dysfunction. The aim of this study was to determine whether gut injury could be demonstrated in sepsis induced by P. aeruginosa and the effects of a PARP inhibitor (PJ34) on the associated gut injury. MATERIALS AND METHODS: After baseline measurements, 20 rabbits were randomized into three groups: Sham (n = 5): transtracheally inoculated (TI) with 2 ml of phosphate buffer solution (PBS); P. aeruginosa + saline (n = 8), TI with 4 x 10(12) CFU/ml of P. aeruginosa in 2 ml/kg of PBS + i.v. saline; and P. aeruginosa + PJ34 (n = 7), TI with 4 x 10(12) CFU/ml of P. aeruginosa and i.v. treatment with PJ34. RESULTS: P. aeruginosa caused a hyperdynamic response with increased blood flow also in the superior mesenteric artery. No significant differences were found in luminal gut lactate concentrations or PCO(2)-gap between groups. Histological specimens showed moderate or diffuse alveolar infiltrate in the P. aeruginosa + saline group (6/8) and in the P. aeruginosa + PJ34 group (6/7). Gut wet-to-dry weight ratio was significantly higher in the P. aeruginosa + saline group than in Shams (7.5 +/- 0.8 versus 6.4 +/- 0.7, P < 0.05) and significantly lower in the P. aeruginosa + PJ34 group (6.1 + 0.5, P < 0.05 versus the other groups). Blood cultures were positive in 1/5 (Sham), 8/8 (P. aeruginosa + saline group) and 4/7 (P. aeruginosa + PJ34 group) (RR 0.57 CI 95% 0.30-1.08). CONCLUSIONS: Pharmacological inhibition of PARP reduces gut inflammation and may limit bacterial translocation.
Animals↗
Microvascular dysfunction as a cause of organ dysfunction in severe sepsis.
Reduced microvascular perfusion has been implicated in organ dysfunction and multiple organ failure associated with severe sepsis. The precise mechanisms underlying microvascular dysfunction remain unclear, but there are considerable experimental data showing reduced microcirculatory flow, particularly of small vessels, and increased heterogeneity. With the development of newer imaging techniques, human studies have also been conducted and have given rise to similar findings. Importantly, the degree of microvascular disturbance and its persistence is associated with poorer outcomes. The ability to influence these changes may result in better outcomes and bedside systems, enabling direct visualization of the microcirculation, which will help in the assessment of ongoing microcirculatory dysfunction and its response to established and new therapeutic interventions.
Animals↗
Noradrenaline and the kidney: foe, friend, or both?
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Animals↗
Pulse pressure variations to predict fluid responsiveness: influence of tidal volume.
OBJECTIVE: To evaluate the influence of tidal volume on the capacity of pulse pressure variation (DeltaPP) to predict fluid responsiveness. DESIGN: Prospective interventional study. SETTING: A 31-bed university hospital medico-surgical ICU. PATIENTS AND PARTICIPANTS: Sixty mechanically ventilated critically ill patients requiring fluid challenge, separated according to their tidal volume. INTERVENTION: Fluid challenge with either 1,000 ml crystalloids or 500 ml colloids. MEASUREMENTS AND RESULTS: Complete hemodynamic measurements including DeltaPP were obtained before and after fluid challenge. Tidal volume was lower than 7 ml/kg in 26 patients, between 7-8 ml/kg in 9 patients, and greater than 8 ml/kg in 27 patients. ROC curve analysis was used to evaluate the predictive value of DeltaPP at different tidal volume thresholds, and 8 ml/kg best identified different behaviors. Overall, the cardiac index increased from 2.66 (2.00-3.47) to 3.04 (2.44-3.96) l/min m(2) ( P <0.001). It increased by more than 15% in 33 patients (fluid responders). Pulmonary artery occluded pressure was lower and DeltaPP higher in responders than in non-responders, but fluid responsiveness was better predicted with DeltaPP (ROC curve area 0.76+/-0.06) than with pulmonary artery occluded pressure (0.71+/-0.07) and right atrial (0.56+/-0.08) pressures. Despite similar response to fluid challenge in low (<8 ml/kg) and high tidal volume groups, the percent of correct classification of a 12% DeltaPP was 51% in the low tidal volume group and 88% in the high tidal volume group. CONCLUSIONS: DeltaPP is a reliable predictor of fluid responsiveness in mechanically ventilated patients only when tidal volume is at least 8 ml/kg.
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Does disseminated intravascular coagulation lead to multiple organ failure?
Microvascular dysfunction with its associated impaired regional oxygen transport and use is believed to be the final common pathway in the development of multiple organ failure. The precise mechanisms underlying this dysfunction, however, are uncertain. Activation of the coagulation system is a key feature in the pathogenesis of sepsis, but whether it is also the cause of multiple organ failure is unclear. This article discusses the evidence for and against a key role for disseminated intravascular coagulation in the pathogenesis of multiple organ failure.
Disseminated Intravascular Coagulation↗