| 1. |
- Carlsson, Markus, et al.
(författare)
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Inflammatory and circulatory effects of the reduction of endotoxin concentration in established porcine endotoxemic shock : a model of endotoxin elimination
- 2009
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 37:3, s. 1031-e4
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction.Design:Prospective parallel-grouped placebo-controlled randomized interventional experimental study.Setting:University research unit.Subjects: Healthy pigs.Interventions:The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 µg endotoxin × kg-1 × h-1 for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively.Measurements and Main Results:During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-[alpha] (TNF-[alpha]) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-[alpha] concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao2, Paco2, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage.Conclusions:Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-[alpha] peak or later will have very little or no effect on TNF-[alpha]–mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.
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| 2. |
- Claesson, Jonas, et al.
(författare)
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Negative mesenteric effects of lung recruitment maneuvers in oleic acid lung injury are transient and short lasting.
- 2007
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 35:1, s. 230-238
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To test the hypothesis that repeated recruitment maneuvers (RMs) have sustained negative effects on mesenteric circulation, metabolism, and oxygenation 60 mins after RMs in pigs with oleic acid lung injury. Further, we aimed to test the hypothesis that an infusion of prostacyclin (PC) at 33 ng.kg.min would attenuate such possible negative mesenteric effects. DESIGN: Randomized, experimental, controlled study. SETTING: University hospital animal laboratory. SUBJECTS: A total of 31 anesthetized, fluid-resuscitated pigs with oleic acid lung injury. INTERVENTIONS: Animals were randomized to one of the following four groups: a control group (n = 7) that received no intervention, recruitment group (n = 8) that underwent the RM sequence, a prostacyclin group (n = 8) that received an infusion of PC, and a recruitment-prostacyclin group (n = 8) that received an infusion of PC and concomitant RM sequence. MEASUREMENTS AND MAIN RESULTS: We measured systemic and mesenteric hemodynamic variables, jejunal mucosal perfusion, mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygen delivery, uptake, and extraction ratio. Five minutes after RMs, mesenteric oxygen extraction ratio and mesenteric lactate flux were more prominently increased in the recruitment group, giving evidence of worsened mesenteric conditions after RMs. These signs of worsened conditions were further supported by more decreased jejunal tissue oxygen tension and portal vein oxygen saturation in the recruitment group. PC preserved mesenteric oxygenation, as indicated by less of a decrease in portal vein oxygen saturation at the time corresponding to 5 mins after RM and less of a decrease in mesenteric oxygen delivery at the time corresponding to 15 mins after RM. PC preserved mesenteric oxygenation as indicated by less of a decrease in portal vein oxygen saturation at 5 mins after RM and an attenuated increase in mesenteric oxygen extraction ratio at 5 mins after RM. There was a trend toward worsened jejunal mucosal perfusion, although not significant. CONCLUSIONS: In an oleic acid lung injury model, three repeated RMs did not improve systemic oxygenation or lung mechanics. Negative effects on mesenteric oxygenation and metabolism were transient and short lasting. The intestinal effects of PC during RMs were minor and opposing, showing preserved oxygenation but a trend toward worsened mucosal perfusion.
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| 3. |
- Da, Jiping, et al.
(författare)
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Nitric oxied up-regulates the glucocorticoid receptor and blunts the inflammatory reaction in porcine endotoxin sepsis
- 2007
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 35:1, s. 26-32
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Nitric oxide inhibits the expression of many genes involved in inflammatory diseases. Glucocorticoids inhibit similar transcription factors. We hypothesized that there may be an interaction between nitric oxide and glucocorticoids, with the potential to enhance the anti-inflammatory effect when administered simultaneously. Design: Prospective, randomized, controlled study. Setting: Animal research laboratory. Subjects: A total of 45 anesthetized and mechanically ventilated pigs. Interventions: Lung and systemic injury was induced by intravenous infusion of endotoxin (lipopolysaccharide) for 6 hrs. After 2.5 hrs, one group received 3.5 mg/kg hydrocortisone, another group inhaled nitric oxide (30 ppm), and still another group received both steroid and nitric oxide. Control groups of healthy and endotoxin-exposed piglets were also studied. Measurements and Main Results: Central hemodynamics and gas exchange were measured. Detection of the glucocorticoid receptor and inflammatory markers in lung, liver, and kidney tissue were made by immunohistochemistry, and morphology was studied with light microscopy. Endotoxin infusion markedly reduced glucocorticoid receptor expression in lung, liver, and kidney and up-regulated activator protein-1 and the inflammatory markers nuclear factor-κB and tumor necrosis factor-a. When administered separately, steroids and nitric oxide had modest effect on the inflammatory response. However, nitric oxide up-regulated the glucocorticoid receptor expression. Simultaneous administration of steroids and nitric oxide attenuated the inflammatory response and almost preserved or restored normal histology of both lung and systemic organs. When the glucocorticoid receptor was blocked by a receptor antagonist (mifepristone, 600 mg) and inhaled nitric oxide was subsequently administered, no increase in the expression of the glucocorticoid receptor was seen. Conclusion: We suggest that up-regulation of glucocorticoid receptor expression by nitric oxide made steroid therapy more effective.
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| 4. |
- Gedeborg, Rolf, 1962-, et al.
(författare)
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The impact of clinically undiagnosed injuries on survival estimates
- 2009
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 37:2, s. 449-55
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:: Missed injury diagnoses may cause potentially preventable deaths. To estimate the effect of clinically undiagnosed injuries on injury-specific survival estimates and the accuracy of an injury severity score. To also estimate the potentially preventable mortality attributable to these injuries. DESIGN, SETTING, AND PATIENTS:: In a nation-wide, population-based study, data were collected from all hospital admissions for injuries in Sweden between 1998 and 2004. We studied 8627 deaths in hospital among 598,137 incident hospital admissions. MEASUREMENTS AND MAIN RESULTS:: New specific-injury categories were added in 7.4% (95% confidence interval [CI] 6.8-8.0) of all deaths with an autopsy rate of 24.2%. It was estimated that this proportion would have increased to 25.1% (95% CI 23.0-27.2), if all deaths had been autopsied. The most pronounced effect of clinically undiagnosed injuries was found for internal organ injury in the abdomen or pelvis, where they reduced the estimated survival from 0.83 to 0.69 (95% CI for the difference: 0.09-0.20). Autopsy diagnoses also revealed substantial bias of survival estimates for vascular injuries in the thorax and crush injuries to the head. The performance of the International Classification of Diseases Injury Severity Score improved when autopsy diagnoses were added to hospital discharge diagnoses. The maximum proportion of injury deaths attributable to missed injuries was estimated to be 6.5%. CONCLUSIONS:: Maintaining a high autopsy rate and merging accurate hospital discharge data and autopsy data are effective ways to improve the accuracy of survival estimates and mortality prediction models, and to estimate mortality attributable to diagnostic failures.
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| 5. |
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| 6. |
- Larsson, Lars
(författare)
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Experimental animal models of muscle wasting in intensive care unit patients
- 2007
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 35:9, s. S484-S487
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Tidskriftsartikel (refereegranskat)abstract
- The muscle wasting and loss of muscle function associated with critical illness and intensive care have significant negative consequences for weaning from the respirator, duration of hospital stay, and quality of life for long periods after hospital discharge. There is, accordingly, a significant demand for focused research aiming at improving our understanding of the mechanisms underlying the impaired neuromuscular function in intensive care unit (ICU) patients. However, the study of generalized muscle weakness in critically ill ICU patients is further complicated by the coexistence of multiple independent factors, such as different primary diseases, large variability in pharmacologic treatment, collection of muscle samples several weeks after admission to the ICU, and exposure to causative agents. This has led to the design of specific animal models mimicking ICU conditions. These models have often been used to study the mechanisms underlying the paralysis and muscle wasting associated with acute quadriplegic myopathy in ICU patients. This short review aims at presenting existing and recently introduced experimental animal models mimicking the conditions in the ICU (i.e., models designed to determine the mechanisms underlying the muscle wasting associated with ICU treatment).
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| 7. |
- Lattuada, Marco, et al.
(författare)
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Abdominal lymph flow in an endotoxin sepsis model : Influence of spontaneous breathing and mechanical ventilation
- 2006
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 34:11, s. 2792-2798
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Lymph flow from the abdomen was investigated in a sepsis model. We also compared the effect on thoracic duct lymph flow of mechanical ventilation with different levels of positive end-expiratory pressure (PEEP) and spontaneous breathing with continuous positive airway pressure (CPAP). DESIGN: Experimental study. SETTING: Research laboratory in a university hospital. SUBJECTS: Thirty-two pigs. INTERVENTIONS: Animals were anesthetized. In study 1 (n = 18), an ultrasonic flow probe was put around the intact thoracic duct just caudal to the diaphragm, and animals were randomized to receive mechanical ventilation with a PEEP of 5 cm H2O or 15 cm H2O or breathed spontaneously in CPAP with a PEEP of 5 cm H2O. In study 2 (n = 6), the thoracic duct was cannulated and the cannula externalized through the abdominal wall for lymph collection; animals were then ventilated as in study 1. In all animals, endotoxin was infused at 15 μg/kg/hr for 2.5 hrs and then continued at 5 μg/kg/hr. In study 3, healthy (n = 4) and endotoxin-exposed (n = 4) pigs had intra-abdominal pressure increased to 27 cm H2O for 2 hrs by pneumoperitoneum. Lymph flow was measured as in study 1. MEASUREMENTS AND MAIN RESULTS: Lymph flow (mean ± se) was 2.5 ± 0.4 mL/min at baseline and increased to 3.9 ± 0.8 mL/min after 90 mins and 6.3 ± 1.6 mL/min after 150 mins (p < .005) of endotoxin exposure. PEEP 15 cm H2O decreased lymph flow in pigs with intact thoracic duct (flow probe recording) and in pigs with cannulated lymph duct when drained against the central venous pressure. However, when drained against atmospheric pressure, PEEP increased flow. Spontaneous breathing increased flow both in intact and in cannulated animals. CONCLUSIONS: Endotoxin increases lymph flow from the abdomen. Mechanical ventilation with high PEEP impedes lymph drainage and could increase lymph production. Spontaneous breathing increases flow and improves drainage of abdominal edema.
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| 8. |
- Lipcsey, Miklós, et al.
(författare)
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Effect of a single dose of tobramycin on systemic inflammatory response-induced acute kidney injury in a 6-hour porcine model
- 2009
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 37:10, s. 2782-2790
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To evaluate whether the addition of tobramycin further compromises renal function in inflammatory response-induced acute kidney injury. Effective antibiotic treatment in septic shock is crucial for the outcome. The combination of aminoglycosides with different beta-lactam antibiotics offers a broad antimicrobial coverage, rapid bacterial killing, synergistic effects, and low antibiotic-induced endotoxin release. However, aminoglycosides have nephrotoxic effects that may aggravate sepsis-induced acute kidney injury.DESIGN:Prospective, randomized, placebo-controlled experimental study.SETTING:University research unit.SUBJECTS:Twenty-four healthy pigs.INTERVENTIONS:The animals were anesthetized and randomized to four groups. Groups I (n = 8) and II (n = 8) received endotoxin infusion for 6 hrs, whereas groups III (n = 4) and IV (n = 4) received saline. Groups I and III received 7 mg/kg of tobramycin 20 mins after the initiation of the protocol, whereas groups II and IV received saline.MEASUREMENTS AND MAIN RESULTS:The renal elimination rate of a bolus dose of cefuroxime was chosen as the primary end point. Renal function was also evaluated by urine output, creatinine clearance, plasma cystatin C, plasma urea, and urine NAG (N-acetyl-beta-D-glucoaminidase). After 3 hrs, there were significantly lower cefuroxime elimination rates in the two endotoxin groups than in the nonendotoxin groups. No difference in cefuroxime elimination rates between groups I and II could be detected at any time point. Similarly, there were changes indicating acute kidney injury in urine output, creatinine clearance, and plasma cystatin C in the endotoxin groups with no differences between groups I and II. Plasma urea and urine NAG did not differ between any of the groups.CONCLUSIONS:The result of this study does not lend any support to the hypothesis that a single dose of tobramycin enhances the risk of acute renal failure in cases with systemic inflammatory response-induced acute kidney injury.
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| 9. |
- Miclescu, Adriana, et al.
(författare)
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Methylene blue added to a hypertonic-hyperoncotic solution increases short-term survival in experimental cardiac arrest
- 2006
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 34:11, s. 2806-2813
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Methylene blue (MB), a free-radical scavenger inhibiting the production and actions of nitric oxide, may counteract excessive vasodilatation induced by nitric oxide during cardiac arrest. Effects of MB in cardiac arrest and cardiopulmonary resuscitation were investigated. DESIGN: Randomized, prospective, laboratory animal study. SETTING: University animal research laboratory. SUBJECTS: A total of 63 piglets of both sexes. INTERVENTIONS: A pig model of extended cardiac arrest (12 mins of untreated cardiac arrest and 8 mins of cardiopulmonary resuscitation) was employed to assess the addition or no addition of MB to a hypertonic saline-dextran solution. These two groups (MB and hypertonic saline-dextran group [MB group] and hypertonic saline-dextran-only group) of 21 animals were each compared with a group receiving isotonic saline (n = 21). MEASUREMENTS AND MAIN RESULTS: Although the groups were similar in baseline values, 4-hr survival in the MB group was increased (p = .02) in comparison with the isotonic saline group. Hemodynamic variables were somewhat improved at 15 mins after restoration of spontaneous circulation in the MB group compared with the other two groups. The jugular bulb levels of 8-isoprostane-prostaglandin F2alpha and 15-keto-dihydro-prostaglandin F2alpha (indicators of peroxidation and inflammation) were significantly decreased in the MB group compared with the isotonic saline group. Significant differences were recorded between the three groups in levels of protein S-100beta (indicator of neurologic injury), with lower levels in the MB group compared with the isotonic saline and hypertonic saline-dextran-only groups. Troponin I and myocardial muscle creatine kinase isoenzyme arterial concentrations (indicators of myocardial damage) were also significantly lower in the MB group. CONCLUSIONS: MB co-administered with a hypertonic-hyperoncotic solution increased 4-hr survival vs. saline in an experimental porcine model of cardiac arrest and reduced oxidative, inflammatory, myocardial, and neurologic injury.
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| 10. |
- Olofsson, Pia, et al.
(författare)
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Gastrointestinal microcirculation and cardiopulmonary function during experimentally increased intra-abdominal pressure
- 2009
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 37:1, s. 230-239
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to assess gastric, intestinal, and renal cortex microcirculation parallel with central hemodynamics and respiratory function during stepwise increase of intra-abdominal pressure (IAP). Design: Prospective, controlled animal study. Setting: Research laboratory, University Hospital. Subjects: Twenty-six anesthetized and mechanically ventilated pigs. Interventions: Following baseline registrations, CO2 peritoneum was inflated (n = 20) and IAP increased stepwise by 10 mm Hg at 10 mins intervals up to 50 mm Hg and subsequently exsufflated. Control animals (n = 6) were not insufflated with CO2. Measurements and Main Results: The microcirculation of gastric mucosa, small bowel mucosa, small bowel seromuscular layer, colon mucosa, colon seromuscular layer, and renal cortex were selectively studied at all pressure levels and after exsufflation using a four-channel laser Doppler flowmeter (Periflex 5000, Perimed). Central hemodynamic and respiratory function data were registered at each level and after exsufflation. Cardiac output decreased significantly at IAP levels above 10 mm Hg. The microcirculation of gastric mucosa, renal cortex and the seromuscular layer of small bowel and colon was significantly reduced with each increase of IAP. The microcirculation of the small bowel mucosa and colon mucosa was significantly less affected compared with the serosa (p < 0.01). Conclusions: Our animal model of low and high IAP by intraperitoneal CO2-insufflation worked well for studies of microcirculation, hemodynamics, and pulmonary function. During stepwise increases of pressure there were marked effects on global hemodynamics, respiratory function, and microcirculation. The results indicate that intestinal mucosal flow, especially small bowel mucosal flow, although reduced, seems better preserved in response to intra-abdominal hypertension caused by CO2-insufflation than other intra-abdominal microvascular beds.
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| 11. |
- Orwelius, Lotti, 1956-, et al.
(författare)
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Role of preexisting disease in patients' perceptions of health-related quality of life after intensive care.
- 2005
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 33:7, s. 1557-1564
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To find out how patients perceive their health-related quality of life after they have been treated in an intensive care unit and whether preexisting disease influenced their perception. DESIGN:: Follow-up, quantitative, dual-site study. SETTING: Combined medical and surgical intensive care units of one university and one general hospital in Sweden. PATIENTS: Among the 1,938 patients admitted, 562 were considered eligible (>24 hrs in the intensive care unit, and age >18 yrs). The effect of preexisting disease was assessed by use of a large reference group, a random sample (n = 10,000) of the main intake area of the hospitals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During 2000-2002, data were collected from the intensive care unit register and from a questionnaire mailed to the patients 6 months after their discharge from hospital. Subjects in the reference group were sent postal questionnaires during 1999. Of the patients in the intensive care unit group, 74% had preexisting diseases compared with 51% in the reference group. Six months after discharge, health-related quality of life was significantly lower among patients than in the reference group. When comparisons were restricted to the previously healthy people in both groups, the observed differences were about halved, and when we compared the patients in the intensive care unit who had preexisting diseases with subjects in the reference group who had similar diseases, we found little difference in perceived health-related quality of life. In some dimensions of health-related quality of life, we found no differences between patients in the intensive care unit and the subjects in the reference population. CONCLUSIONS: Preexisting diseases significantly affect the extent of the decline of health-related quality of life after critical care, and this effect may have been underestimated in the past. As most patients who are admitted to an intensive care unit have at least one preexisting disease, it is important to account for these effects when examining outcome.
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| 12. |
- Sackey, Peter, et al.
(författare)
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Short- and long-term follow-up of intensive care unit patients after sedation with isoflurane and midazolam : A pilot study
- 2008
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 36:3, s. 801-806
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare memories from the intensive care unit (ICU) and short- and long-term psychological morbidity in patients after sedation with intravenous midazolam or inhaled isoflurane. DESIGN: Prospective long-term follow-up after randomized controlled trial. SETTING: General ICU at Karolinska University Hospital, Solna, Stockholm. PATIENTS: Forty patients in need of sedation during ventilator treatment. INTERVENTIONS: Patients were randomized to receive isoflurane or midazolam for goal-directed sedation until extubation or for a maximum of 96 hrs. MEASUREMENTS AND MAIN RESULTS: For short-term follow-up, doctors', nurses', and physiotherapists' notes from the 4 days following exposure to the study drugs were reviewed for words indicating adequate or pathologic cognitive and psychological recovery. For long-term follow-up, all 6-month survivors received questionnaires including the ICU Memory Tool (ICU-MT), Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), and Well-Being Index. Additionally, several screening questions for previous posttraumatic stress symptoms were included. In the short term follow-up, no significant differences were found between groups. In the long-term follow-up, a trend toward fewer hallucinations/delusions after isoflurane sedation than after midazolam (two of ten isoflurane patients vs. five of seven midazolam patients) was found (p = .06). None of the five solely isoflurane-sedated patients reported hallucinations/delusions from the ICU. There was no difference in groups in long-term psychological morbidity as measured with HADS and IES. Memories of negative feelings in the ICU (ICU-MT) were associated with high HADS and IES scores (Fisher's exact test, p = .02 and p = .01, respectively). CONCLUSIONS: Sedation of ICU patients with isoflurane may result in fewer delusional memories or hallucinations from the ICU compared with more commonly used intravenous sedation. Memories of negative feelings from the ICU were associated with symptoms of depression or anxiety or symptoms indicating posttraumatic stress disorder. Further study of memory and cognitive/psychological recovery after prolonged isoflurane sedation beyond 96 hrs is warranted.
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| 13. |
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| 14. |
- Suarez-Sipmann, Fernando, et al.
(författare)
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Use of dynamic compliance for open lung positive end-expiratory pressure titration in an experimental study
- 2007
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 35:1, s. 214-221
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We tested whether the continuous monitoring of dynamic compliance could become a useful bedside tool for detecting the beginning of collapse of a fully recruited lung. Design: Prospective laboratory animal investigation. Setting: Clinical physiology research laboratory, University of Uppsala, Sweden. Subjects: Eight pigs submitted to repeated lung lavages. Interventions: Lung recruitment maneuver, the effect of which was confirmed by predefined oxygenation, lung mechanics, and computed tomography scan criteria, was followed by a positive end-expiratory pressure (PEEP) reduction trial in a volume control mode with a tidal volume of 6 mL/kg. Every 10 mins, PEEP was reduced in steps of 2 cm H2O starting from 24 cm H2O. During PEEP reduction, lung collapse was defined by the maximum dynamic compliance value after which a first measurable decrease occurred. Open lung PEEP according to dynamic compliance was then defined as the level of PEEP before the point of collapse. This value was compared with oxygenation (PaO2) and CT scans. Measurements and Main Results: PaO2 and dynamic compliance were monitored continuously, whereas computed tomography scans were obtained at the end of each pressure step. Collapse defined by dynamic compliance occurred at a PEEP of 14 cm H2O. This level coincided with the oxygenation-based collapse point when also shunt started to increase and occurred one step before the percentage of nonaerated tissue on the computed tomography exceeded 5%. Open lung PEEP was thus at 16 cm H2O, the level at which oxygenation and computed tomography scan confirmed a fully open, not yet collapsed lung condition. Conclusions: In this experimental model, the continuous monitoring of dynamic compliance identified the beginning of collapse after lung recruitment. These findings were confirmed by oxygenation and computed tomography scans. This method might become a valuable bedside tool for identifying the level of PEEP that prevents end-expiratory collapse.
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| 15. |
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| 16. |
- Wang, Jianpu, 1957-, et al.
(författare)
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Effects of endothelin receptor antagonism on acute lung injury induced by chlorine gas
- 2006
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 34:6, s. 1731-1737
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To test the hypothesis that the endothelin system is involved in chlorine gas-induced lung injury.DESIGN: Experimental study.SETTING: Academic research laboratory.SUBJECTS: Twenty-four domestic juvenile pigs.INTERVENTIONS: Anesthetized, ventilated pigs were exposed to chlorine gas (400 parts per million in air) for 20 mins and then randomly allocated to four groups (n = 6 in each group). The tezosentan pretreatment group received the dual endothelin receptor antagonist tezosentan 20 mins before and hyperoxic gas (Fio2 0.6) after chlorine gas exposure. The tezosentan postinjury treatment group received hyperoxic gas after chlorine gas exposure and tezosentan 60 mins later. Animals in the oxygen group received hyperoxic gas after chlorine gas exposure. Pigs in the fourth group (air) were ventilated with room air (Fio2 0.21) throughout the experiment.MEASUREMENTS AND MAIN RESULTS: Hemodynamics, gas exchange, lung mechanics, and plasma endothelin-1 were evaluated for 6 hrs. Chlorine gas exposure induced an increase in circulating endothelin-1 by 90% (p < .05). The acute chlorine gas-induced rise in pulmonary vascular resistance was partly blocked by tezosentan pretreatment (p < .001). Tezosentan postinjury treatment also decreased pulmonary vascular resistance to levels significantly lower than in the air and oxygen groups (p < .001). Recovery of peak airway pressure was better in the tezosentan-treated groups than in the air group. There were significant linear relationships between circulating endothelin-1 and pulmonary vascular resistance (r = .47, p < .001) and endothelin-1 and peak airway pressure (r = .41, p < .001). These relationships were modified by tezosentan.CONCLUSIONS: Tezosentan modified chlorine gas-induced pulmonary dysfunction, indicating that the endothelin system is involved in this mode of acute lung injury.
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| 17. |
- Wrigge, Hermann, et al.
(författare)
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Electrical impedance tomography compared with thoracic computed tomography during a slow inflation maneuver in experimental models of lung injury
- 2008
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 36:3, s. 903-909
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the validity of functional electric impedance tomography to monitor regional ventilation distribution in experimental acute lung injury, and to develop a simple electric impedance tomography index detecting alveolar recruitment. DESIGN: Randomized prospective experimental study. SETTING: Academic research laboratory. SUBJECTS: Sixteen anesthetized, tracheotomized, and mechanically ventilated pigs. INTERVENTIONS: Acute lung injury was induced either by acid aspiration (direct acute lung injury) or by abdominal hypertension plus oleic acid injection (indirect acute lung injury) in ten pigs. Six pigs with normal lungs were studied as a control group and with endotracheal suction-related atelectasis. After 4 hrs of mechanical ventilation, a slow inflation was performed. MEASUREMENTS AND MAIN RESULTS: During slow inflation, simultaneous measurements of regional ventilation by electric impedance tomography and dynamic computed tomography were highly correlated in quadrants of a transversal thoracic plane (r2 = .63-.88, p < .0001, bias <5%) in both direct and indirect acute lung injury. Variability between methods was lower in direct than indirect acute lung injury (11 +/- 2% vs. 18 +/- 3%, respectively, p < .05). Electric impedance tomography indexes to detect alveolar recruitment were determined by mathematical curve analysis of regional impedance time curves. Empirical tests of different methods revealed that regional ventilation delay, that is, time delay of regional impedance time curve to reach a threshold, correlated well with recruited volume as measured by CT (r2 = .63). Correlation coefficients in subgroups were r2 = .71 and r2 = .48 in pigs with normal lungs with and without closed suction related atelectasis and r2 = .79 in pigs subject to indirect acute lung injury, respectively, whereas no significant correlation was found in pigs undergoing direct acute lung injury. CONCLUSIONS: Electric impedance tomography allows assessment of regional ventilation distribution and recruitment in experimental models of direct and indirect acute lung injury as well as normal lungs. Except for pigs with direct acute lung injury, regional ventilation delay determined during a slow inflation from impedance time curves appears to be a simple index for clinical monitoring of alveolar recruitment.
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| 18. |
- Asaduzzaman, Muhammad, et al.
(författare)
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Critical role of p38 mitogen-activated protein kinase signaling in septic lung injury.
- 2008
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Ingår i: Critical Care Medicine. - 1530-0293. ; 36:2, s. 482-488
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Leukocyte-mediated tissue damage is a key feature in septic lung injury, although the signaling mechanisms behind pulmonary recruitment of leukocytes remain elusive. The aim of the present study was to define the role of p38 mitogen-activated protein kinase (MAPK) signaling in septic lung injury. DESIGN: Prospective experimental study. SETTING: University hospital research unit. SUBJECTS: Male C57BL/6 mice. INTERVENTIONS: Pulmonary edema, bronchoalveolar infiltration of leukocytes, levels of myeloperoxidase, and CXC chemokines were determined 6 and 24 hrs after cecal ligation and puncture (CLP). The specific p38 MAPK inhibitors SB 239063 and SKF 86002 were given immediately before CLP induction. Phosphorylation and activity of p38 MAPK were determined by immunoprecipitation and Western blot. MEASUREMENTS AND MAIN RESULTS: CLP induced clear-cut pulmonary damage characterized by edema formation, leukocyte infiltration, and increased levels of CXC chemokines in the lung. Moreover, CLP increased phosphorylation and activity of p38 MAPK in the lung, which was markedly inhibited by SB 239063. Interestingly, inhibition of p38 MAPK signaling protected against CLP-induced lung damage and edema. Indeed, both SB 239063 and SKF 86002 decreased CLP-induced leukocyte recruitment in the bronchoalveolar space and formation of CXC chemokines in the lung. CONCLUSIONS: Our data demonstrate that p38 MAPK signaling constitutes a key role in regulating CXC chemokine production in septic lung injury and that inhibition of p38 MAPK activity abolishes pulmonary infiltration of leukocytes as well as lung edema. These novel findings suggest that targeting the p38 MAPK signaling pathway may pave the way for a new therapeutic strategy against lung injury in polymicrobial sepsis.
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| 32. |
- Muhammad, Asad, et al.
(författare)
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Platelets support pulmonary recruitment of neutrophils in abdominal sepsis
- 2009
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Ingår i: Critical Care Medicine. - 1530-0293. ; 37:4, s. 1389-1396
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Recent findings Indicate that platelets not only regulate thrombosis and hemostasis but may also be involved in proinflammatory activities. Herein, we hypothesized that platelets may play a role in sepsis by activating and priming circulating neutrophils for subsequent recruitment Into the lung. Design: Prospective experimental study. Setting. University Hospital Research Unit. Subject. Male C57BL/6 mice. Interventions. Lung edema, bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, expression and function of membrane-activated complex-1 (Mac-1) on neutrophils and the CXC chemokines, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant were determined after cecal ligation and puncture (CLP). Mice received a platelet-depleting antibody as well as antibodies directed against P-selectin glycoprotein-ligand-1 and Mac-1 before CLP induction. Measurements and Main Results. CLP caused significant pulmonary damage characterized by neutrophil infiltration, increased levels of CXC chemokines, and edema formation in the lung. Furthermore, CLP up-regulated Mac-1 expression on neutrophils and increased the number of neutrophils binding platelets in the circulation. Interestingly, depletion of platelets reduced CLP-induced edema and neutrophil recruitment in the bronchoalveolar space by >60%. Furthermore, depletion of platelets reduced Mac-1 expression on neutrophils. On the other hand, inhibition of P-selectin glycoprotein-ligand-1 abolished CLP-induced neutrophil-platelet aggregation but had no effect on neutrophil expression of Mac-1. Conclusions: These data demonstrate that platelets play a key role in regulating infiltration of neutrophils and edema formation in the lung via upregulation of Mac-1 in abdominal sepsis. (Crit Care Med 2009; 37:1389-1396)
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| 33. |
- Muller, Christophe, et al.
(författare)
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Role of endogenous glucocorticoid metabolism in human acute pancreatitis*
- 2006
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Ingår i: Critical Care Medicine. - 1530-0293. ; 34:4, s. 1060-1066
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to observe how levels of total cortisol, calculated free cortisol, corticosteroid-binding globulin, and adrenocorticotropic hormone change during the early course of human acute pancreatitis and to describe how these changes affect the development of pancreatic necrosis. Design and Patients: In a total of 109 consecutive patients with acute pancreatitis (74 with edematous pancreatitis, 35 with necrotizing pancreatitis), serial daily blood monitoring of total and free cortisol, adrenocorticotropic hormone, and corticosteroid-binding globulin was done after hospital admission, up to day 6 after the onset of pain; 30 healthy individuals served as controls. Measurements. Corticosteroid-binding globulin and total cortisol were measured by immunoassays, and free cortisol was calculated according to Coolens et al. The adrenocorticotropic hormone was measured with an enzyme-linked immunoassay. Results, Initially, highly elevated levels of calculated free cortisol (median, 86.2 ng/mL; quartile ranges, 50.6-106.7 ng/mL) and total cortisol (41.2 mu g/dL, 30.4-51.1 mu g/dL) and depressed levels of adrenocarticotropic hormone (0.2 pg/mL, 0.1-2.0 pg/mL) and corticosteroid-binding globulin (30.6 mu g/mL, 24.1-35.5 mu g/mL) were observed. Further, daily measurements revealed increasing adrenocorticotropic hormone levels, whereas cortisol levels decreased. Conclusions: Although an increase in adrenocorticotropic hormone levels is suggested to increase corresponding cortisol levels, cortisol levels decreased during the development of necrotizing acute pancreatitis. This phenomenon, along with the continuously decreasing corticosteroid-binding globulin levels, brings up the hypothesis of a relative adrenal insufficiency, which favors acinar cell apoptosis and hence may trigger the development of necrosis in the initial vulnerable phase of acute pancreatitis.
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| 35. |
- Nygren, Andreas, 1967, et al.
(författare)
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Vasopressors and intestinal mucosal perfusion after cardiac surgery: Norepinephrine vs. phenylephrine.
- 2006
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Ingår i: Critical care medicine. - 0090-3493. ; 34:3, s. 722-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate the potential differential effects of norepinephrine, an alpha1-, beta1-, and beta2-receptor agonist, to the alpha1-agonist phenylephrine on jejunal mucosal perfusion, gastric-arterial PCO2 gradient, and the global splanchnic oxygen demand-supply relationship after cardiac surgery. DESIGN: A randomized, prospective, interventional crossover study. SETTING: A university cardiothoracic intensive care unit. PATIENTS: Ten patients were studied during propofol sedation and mechanical ventilation after uncomplicated coronary artery bypass surgery. INTERVENTIONS: Each patient received randomly and sequentially norepinephrine (0.052+/-0.009 microg/kg/min) and phenylephrine (0.50+/-0.22 microg/kg/min) to increase mean arterial blood pressure by 30%. MEASUREMENTS AND MAIN RESULTS: Data on jejunal mucosal perfusion, jejunal mucosal hematocrit, and red blood cell velocity (laser Doppler flowmetry) as well as gastric-arterial Pco2 gradient (tonometry) and splanchnic oxygen extraction were obtained before (control) and during a 30-min drug infusion period after the target mean arterial blood pressure was reached. The procedure was sequentially repeated for the second vasopressor. Both drugs induced a 40-46% increase in systemic vascular resistance with no change in cardiac index. Neither jejunal mucosal perfusion, jejunal mucosal hematocrit, red blood cell velocity, nor gastric-arterial Pco2 gradient was affected by any of the vasopressors. Splanchnic oxygen extraction increased from 38.2% to 43.1% (p<.001) with norepinephrine and from 39.3% to 47.5% (p<.001) with phenylephrine. This increase was significantly more pronounced with phenylephrine compared with norepinephrine (p<.05). Mixed venous-hepatic vein oxygen saturation gradient increased with both drugs (p<.01), and the increase was more pronounced with phenylephrine (p<.05). Splanchnic lactate extraction was not significantly affected by any of the vasopressors. CONCLUSIONS: Phenylephrine induced a more pronounced global alpha1-mediated splanchnic vasoconstriction compared with norepinephrine. Neither of the vasoconstrictors impaired perfusion of the gastrointestinal mucosa in postcardiac surgery patients. The lack of norepinephrine-induced, alpha1-mediated impairment of gastrointestinal perfusion is not explained by a beta2-mediated counteractive vasodilation but instead by possible mucosal autoregulatory escape.
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| 36. |
- Persson, Johan, et al.
(författare)
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Plasma volume expansion and transcapillary fluid exchange in skeletal muscle of albumin, dextran, gelatin, hydroxyethyl starch, and saline after trauma in the cat
- 2006
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Ingår i: Critical Care Medicine. - 1530-0293. ; 34:9, s. 2456-2462
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare 5% albumin, 6% dextran 70, 3.5% gelatin, 6% hydroxyethyl starch 130/0.4, and saline regarding their plasma volume expanding effect after a surgical skeletal muscle trauma and their simultaneous effects on transvascular fluid exchange in skeletal muscle. Design: Controlled, prospective, randomized laboratory study. Setting: University research laboratory. Subjects: Thirty-six adult cats. Interventions: Systemic arterial pressure and tissue volume variations of and blood flow to a surgically isolated and autoperfused calf muscle placed in a plethysmograph were recorded. Arterial and venous pressures to the muscle were kept constant. After preparation, plasma volumes were determined by a 125 1 albumin tracer technique just before and 3 hrs after a bolus infusion of the plasma expander (25 mL/kg). Measurements and Main Results: Plasma volume was 20.9 +/- 2.9 mL/kg (n = 36) just before infusion of the plasma expander (normal plasma volume for the cat is 34-37 mL/kg). The remaining volume expansion of the infusion after 3 hrs was 6.8 mL/kg for albumin, 11.2 mL/kg for dextran, 1.8 mL/kg for gelatin, 2.2 mL/kg for hydroxyethyl starch, and 0.9 mL/kg for saline. Plasma volume decreased by 1.1 mL/kg when no solution was given (n = 6 per group). Colloid osmotic pressure was better preserved with dextran and albumin than with the other solutions. Albumin and dextran reduced muscle volume by absorption after 3 hrs, whereas the initial absorption turned to net filtration in the gelatin and hydroxyethyl starch groups. Saline infusion increased muscle volume by filtration for about 20 mins, followed by an approximately constant volume. Conclusion: The relatively poor plasma expansion for all solutions analyzed can most likely be explained by increased transcapillary leakage due to increased microvascular permeability following trauma. Under such circumstances, for equal volumes, plasma expansion was better preserved with 6% dextran 70 than with 5% albumin, which was better than 3.5% gelatin, 6% hydroxyethyl starch 130/0.4, and saline.
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| 49. |
- Wernerman, J
(författare)
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May nutrition be hazardous in sepsis?
- 2009
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Ingår i: Critical care medicine. - 1530-0293. ; 37:1, s. 353-354
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 50. |
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