The use of electroconvulsive therapy in a patient with juvenile systemic lupus erythematosus and catatonia.

Catatonia is a rare manifestation in patients with systemic lupus erythematosus (SLE). As catatonia can be associated with both psychiatric and organic conditions, this could create a diagnostic dilemma once this occurs in SLE patients. The report describes a 15-year-old female with SLE who developed catatonia three days after the diagnosis of SLE was made. Her catatonia was refractory to the treatment with immunosuppressive therapy, which included pulse methylprednisolone, intravenous cyclophosphamide, rituximab, intravenous immunoglobulin (IVIG) and plasmapheresis. Given her persistent catatonia, electroconvulsive therapy (ECT) was initiated three months after the onset of her symptoms. After the third ECT treatment, her mental status dramatically improved and returned nearly to baseline while she was continued on the immunosuppression. This is the first report of a successful ECT therapy in catatonic lupus in children.

Estrogenic regulation of S6K1 expression creates a positive regulatory loop in control of breast cancer cell proliferation.

The 40S ribosomal S6 kinase 1 (S6K1) is an important regulator of cell growth. Expression of S6K1 is often elevated in breast cancer cells. However, the transcriptional mechanism of S6K1 overexpression is not understood. In this report, we demonstrate that estrogen activates expression of S6K1 via estrogen receptor (ER)α in ER-positive breast cancer cells. We also show that estrogen acts on the proximal promoter of the S6K1 gene in a mechanism involving the transcriptional factor GATA-3. Finally, we provide data that support the importance of estrogenic regulation of S6K1 expression in breast cancer cell proliferation. S6K1 directly phosphorylates and regulates ligand-independent activity of ERα, while ERα upregulates S6K1 expression. This S6K1-ERα relationship creates a positive feed-forward loop in control of breast cancer cell proliferation. Furthermore, the co-dependent association between S6K1 and ERα may be exploited in the development of targeted breast cancer therapies.

[Postpyloric feeding tubes for surgical intensive care patients. Pilot series to evaluate two methods for bedside placement]. / Postpylorische Ernährungssonden bei operativen Intensivpatienten. Pilotserie zur Bewertung von zwei Methoden zur bettseitigen Anlage.

Bedside placement of postpyloric feeding tubes in surgical intensive care patients: a pilot series to evaluate two methods. Early enteral feeding is thought to be a key factor in maintaining the integrity of the gastrointestinal tract mucosal barrier associated with less bacterial translocation and decreased stimulation of the systemic inflammatory response and subsequent improved outcome in intensive care patients. Thus enteral feeding by nasogastric tubes is the preferred route of nutritional support for most surgical intensive care patients. However, intensive care patients with delayed gastric emptying and poor intestinal motility may not tolerate gastric feeding and may therefore benefit from postpyloric feeding. Postpyloric feeding tube placement may be achieved by endoscopic procedures or different bedside techniques with variable success. In the present study two feeding tubes for bedside postpyloric placement without endoscopic assistance were compared. The time to successful positioning was compared for jejunal feeding tubes from the companies Cook (Tiger 2™) and PortaMedical (Corflo-Tube®). The description for the Tiger 2™ states that because of its design slight residual peristalsis can cause it to migrate from the stomach to the jejunum. The Corflo-Tube® is also positioned at the bedside with the help of a detector and a monitor which maps the movements of the magnetic tip of the mandrin as it is pushed forward. Patients receiving early enteral nutrition through a gastric tube and exhibiting enhanced reflux, in spite of the head of the bed being raised and the administration of prokinetics randomly received either a Tiger 2™ or a Corflo-Tube®. The study included 41 patients from an intensive care ward for surgical patients and 13 out of 20 Tiger 2™-Tubes (65%) and 16 out of 21 Corflo-Tubes® (76%) were successfully positioned (p>0.05). The median time to successful positioning with the Corflo-Tubes® was 0.83 h (range 0.06-2.5 h), which was significantly shorter than the 24 h (range 2-72 h) found with the Tiger 2™ (p<0.001). There was no significant difference between the groups with respect to the period between the insertion of the tubes and the attainment of complete enteral nutrition, corresponding to the calculated individual calorie requirements. These tubes offer a good alternative to more demanding procedures as they are easy to handle and rapidly available. They confer clinical and cost advantages in terms of the early establishment of enteral feeding, no routine X-ray confirmation in the case of the Corflo-Tube® and avoidance of endoscopic guidance for tube placement or parenteral nutrition. In addition they are always justified in the event of a lack of endoscopic positioning.

[Bronchial asthma and chronic obstructive pulmonary disease with acute exacerbation: preclinical differential diagnostic and emergency treatment]. / Asthma bronchiale und chronisch obstruktive Lungenerkrankung mit akuter Exazerbation: Präklinische Differenzialdiagnostik und Notfalltherapie.

Chronic obstructive pulmonary disease (COPD) and bronchial asthma are the most common causes of obstructive pulmonary diseases and acute dyspnoea. In the preclinical emergency situation a distinction between bronchial asthma and exacerbated COPD is difficult because symptoms are similar. Although the preclinical measures differ only marginally, a differential diagnosis from other causes of respiratory obstruction and acute dyspnoea, such as cardiac decompensation, anaphylaxis, aspiration of foreign bodies, tension pneumothorax and inhalation trauma is necessary because alternative treatment options are required. In the treatment of COPD and bronchial asthma inhalative bronchodilatory beta(2)-mimetics are the first choice especially for serious obstructive emergencies because there is an unfavorable relationship between effect and side-effects for the intravenous route. Dosable aerosols, nebulization and if necessary, continuous nebulization, are appropriate application forms even for serious obstructive crises with the need of a respirator. In these cases a minimal inspiratory flow in patients is not required. Theophylline only plays a minor role to beta(2)-mimetics and anticholinergics as a bronchodilator in asthma and COPD guidelines, even in serious obstructive diseases. For severe asthma attacks the administration of magnesium is a possible additional option. Systemic intravenous administration of steroids has an anti-inflammatory effect and for this reason is the second column of treatment for both diseases. Invasive ventilation remains a last resort to ensure respiratory function and indications for this are given in patients with clinical signs of impending exhaustion of breathing.

Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study.

BACKGROUND: Adequate indication and duration of administration are central issues of modern antibiotic treatment in intensive care medicine. The biochemical variable procalcitonin (PCT) is known to indicate systemically relevant bacterial infections with high accuracy. In the present study, we aimed to investigate the clinical usefulness of PCT for guiding antibiotic treatment in surgical intensive care patients with severe sepsis. PATIENTS AND METHODS: Patients were randomly assigned to a PCT-guided or a control group requiring antibiotic treatment. All patients received a calculated antibiotic regimen according to the presumed microbiological spectrum. In the PCT-guided group, antibiotic treatment was discontinued if clinical signs of infection improved and the PCT value was either <1 ng/ml or decreased to <35% of the initial concentration within three consecutive days. In the control group, antibiotic treatment was directed by empirical rules. RESULTS: The PCT-guided group (n = 14 patients) and the control group (n = 13 patients) did not differ in terms of biological variables, underlying diseases, and overall disease severity. PCT guidance led to a significant reduction of antibiotic treatment from 6.6 +/- 1.1 days (mean +/- SD) compared with 8.3 +/- 0.7 days in control patients (p < 0.001) along with a reduction of antibiotic treatment costs of 17.8% (p < 0.01) without any adverse effects on outcome. CONCLUSIONS: Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients with severe sepsis. This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistances and costs in intensive care medicine.

[Antibiotic treatment of surgical intensive care patients: procalcitonin to guide duration of therapy]. / Antibiotikatherapie bei operativen Intensivpatienten: Prokalzitonin zur Steuerung der Therapiedauer.

The development of resistance by infective bacterial species is an incentive to reconsider the indications and administration of available antibiotics. Correct recognition of the indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care situation. There has as yet been no clinical chemical parameter which is capable of specifically distinguishing a bacterial infection from a viral or non-infectious inflammatory reaction, but it now appears that procalcitonin (PCT) offers this possibility. The present study was intended to clarify whether PCT can be used to guide antibiotic therapy in surgical intensive care patients. A total of 110 patients in a surgical intensive care ward receiving antibiotic therapy after confirmed infection or a high grade suspicion of infection were enrolled in this study. In 57 of these patients a new decision was reached each day as to whether the antibiotic therapy should be continued after daily PCT determination and clinical assessment. The control group consisted of 53 patients with a standardized duration of antibiotic therapy over 8 days. Demographic and clinical data were comparable in both groups. However, in the PCT group the duration of antibiotic therapy was significantly shorter compared to controls (5.9+/-1.7 vs. 7.9+/-0.5 days, p<0.001) without unfavorable effects on clinical outcome.

[Nasojejunal enteral feeding tubes in critically ill patients. Successful placement without technical assistance]. / Nasojejunale Ernährungssonden bei Intensivpatienten. Erfolgreiche Platzierung ohne technische Hilfsmittel.

BACKGROUND: Critically ill patients with early enteral feeding seem to profit from post-pyloric administration. Two feeding tubes were studied that, due to their construction, are able to move into the duodenum without the necessity of technical support. The duration until successful positioning, time until total enteral feeding and possible complications were compared. PATIENTS AND METHOD: Patients with naso-gastric tubes and early enteral feeding, who had an increased reflux despite head of bed elevation and prokinetic drugs, were randomly assigned to either a Tiger tube (Cook) or a Bengmark tube (Pfrimmer Nutricia). RESULTS: A total of 28 patients from the surgical intensive care ward were included. Of the 16 Tiger tubes 14 could be successfully placed but only 2 out of the 12 Bengmark tubes. With Tiger tubes total enteral feeding was established within 6 days (median), with Bengmark tubes within 4 days. CONCLUSION: In comparison to the Bengmark tube the Tiger tube has a higher success rate in terms of positioning in intensive care patients with impaired abdominal motility.

Interleukin-6 enhancement after direct autologous retransfusion of shed thoracic blood does not influence haemodynamic stability following coronary artery bypass grafting.

BACKGROUND: Direct autologous retransfusion of shed thoracic blood is carried out to reduce homologous transfusion after cardiac surgery, but it contains high concentrations of inflammatory mediators. The purpose of the study was to investigate whether retransfusion of shed thoracic blood induces plasma interleukin-6 (IL-6) expression and influences haemodynamics. METHODS: Following uncomplicated coronary artery bypass graft surgery, forty-four patients were randomised in case postoperative blood loss via thoracic drains exceeded 350 ml. The course of plasma IL-6 levels and haemodynamics including cardiac output, extravascular lung water and intrathoracic blood volume were investigated prior to (T0), 30 minutes (T1), 1 (T2), 3 (T3) and 12 hours (T4) after retransfusion of 350 ml shed blood in comparison to 350 ml saline. RESULTS: Plasma IL-6 levels at T1 (1892 +/- 202 vs. 485 +/- 30 pg/ml) and T2 (1059 +/- 119 vs. 413 +/- 30 pg/ml) were significantly higher in the verum group (n = 20) compared to controls (n = 24) ( P < 0.01). Severe haemodynamic side effects were not detected. CONCLUSION: This study found significantly elevated plasma IL-6 levels following direct autologous retransfusion of shed thoracic blood but failed to show severe adverse effects affecting haemodynamic stability.

[Studies on low protein C-expression in severe sepsis]. / Untersuchungen zur verminderten Protein-C-Expression in der schweren Sepsis.

OBJECTIVES: Low concentration of protein C in severe sepsis may be associated with increased morbidity and mortality. The present study was designed to clarify to what extent there are differences in the time course of plasma concentrations of protein C in patients with systemic inflammatory response syndrome or patients with severe sepsis. In addition, the cause of decreased expression of protein C in severe sepsis was examined. METHODS: 32 patients with severe sepsis and 10 patients with systemic inflammatory response syndrome admitted to a surgical intensive care unit were enrolled in the study. While the patients stayed in the intensive care unit protein C plasma concentrations and the clotting factors thrombin-antithrombin-complex and factor VII were determined twice weekly. RESULTS: Comparing patients with severe sepsis and systemic inflammatory response syndrome there was no significant difference concerning plasma levels of protein C, thrombin-antithrombin-complex and factor VII. In contrast, surviving patients with severe sepsis exhibited significant higher protein C levels compared to non-survivors. In addition, significant lower plasma levels of thrombin-antithrombin-complex were determined in survivors compared to non-survivors. However, factor VII displayed no significant group difference. CONCLUSIONS: Surviving patients with severe sepsis exhibited higher plasma concentrations of protein C than patients who died during severe sepsis. The lower plasma concentrations of protein C in non-survivors may be caused by an increased turnover of protein C served as endogenous anticoagulant in sepsis associated activation of coagulation.

Schmidt syndrome presenting as acute liver failure.

The Schmidt Syndrome (Type II Autoimmune-Syndrome) is characterised by an autoimmune adrenalitis in combination with a chronic lymphocellular thyreoiditis resulting in insufficiency of these organs in adulthood. Combination with diabetes is possible. The diagnosis is usually established by clinical examination and analysis of serum hormone levels (adrenocorticotropin hormone [ACTH], cortisol, thyroid stimulating hormone [TSH], triiodothyronine [fT3], thyroxine [fT4]). In the present case, initial diagnosis was rapid progressive liver failure of unknown origin with consecutive multiple organ dysfunction syndrome including dysfunction of heart, lungs, and kidneys. Frequent and less frequent causes of liver failure were ruled out, e.g. viral or autoimmune hepatitis, Budd-Chiari-syndrome, toxic, or drug induced liver failure. In retrospect, the multiple organ dysfunction syndrome was caused by hypoperfusion due to severe hypovolemia and hypoperfusion was induced by adrenocortical insufficiency proven by endocrinological testing. The clinical course of this case stresses the importance of the hormone balance in the critical ill patient. The guideline for treatment of patients with assumed hormonal dysregulation should include a full hormone status prior to substitution. The present case report also illustrates the importance of clinical signs and careful consideration of the medical history in detecting an autoimmune endocrine disease.

[Relevance of wound drainage in total knee arthroplasty--a prospective comparative study]. / Die Bedeutung der Wunddrainage in der Knieendoprothetik--eine prospektive Vergleichsstudie.

AIM: The benefits of postoperative wound drainage in patients with total knee arthroplasty (TKA) with regards to mobilisation and wound healing were studied. We wanted to determine the efficacy of an autologous blood retransfusion system. METHOD: 150 patients with TKA were divided into three groups of 50 patients: A) three wound drainages with an autotransfusion system and suction; B) no wound drainage; C) one intraarticular wound drainage without suction. Hemoglobin values, blood transfusion requirements, blood loss, postoperative range of motion, Insall knee score and rate of complications were observed and recorded. All patients were operated without tourniquets for lower blood loss. RESULTS: In the group of patients with wound drainage and a retransfusion system the requirement of postoperative additional blood transfusion was not significantly less than in the group without wound drainage. Group A had the highest blood loss of all. The group without wound drainage had more hematomas and wound healing complications. Best results were observed within the group with one intraarticular drainage without suction. The rate of complications was not increased and the blood transfusion requirements were the lowest. CONCLUSION: This study shows that total knee replacement involving one intraarticular wound drainage without suction attains the best results.

Effects of induction of anaesthesia with sufentanil and positive-pressure ventilation on the intra- to extrathoracic volume distribution.

BACKGROUND AND OBJECTIVE: Induction of general anaesthesia in combination with positive-pressure ventilation is often associated with a significant decrease of arterial pressure. A decreased preload may contribute to this phenomenon. The aim was to investigate whether a change in cardiac filling occurs following the induction of general anaesthesia with sufentanil under typical clinical conditions. METHODS: Fifteen patients scheduled for elective coronary bypass grafting were studied immediately before surgery. In addition to standard monitors, a transpulmonary double-indicator dilution technique measured in vivo intrathoracic blood volume, global end-diastolic volume and total circulating blood volume. For induction of anaesthesia 2 microg kg(-1) sufentanil was given. Measurements were performed awake and after the induction of anaesthesia, intubation and mechanical ventilation of the lungs. RESULTS: To maintain arterial pressure during the induction period within -20% of baseline pressure, on average 22 +/- 6mLkg(-1) crystalloids and 8 +/- 6mLkg(-1) colloids were given. Despite these amounts of fluid, cardiac filling was decreased, whereas circulating blood volume increased significantly. Both central venous pressure and pulmonary capillary wedge pressure increased. CONCLUSIONS: Induction of general anaesthesia with positive-pressure ventilation is regularly associated with a blood volume shift from intra- to extrathoracic compartments. Even in low-dose opioid monoanaesthesia with sufentanil--often regarded as relatively inert in haemodynamic terms--the phenomenon could be demonstrated as the primary cause of the often-observed decrease of arterial pressure. It seems, therefore, rationally justified to restore cardiac filling by generous administration of intravenous fluids, at least in patients with unaffected cardiac pump function. During induction of anaesthesia, central venous pressure and pulmonary capillary wedge pressure do not reliably indicate cardiac filling.

Perioperative monitoring of indocyanine green clearance and plasma disappearance rate in patients undergoing liver transplantation.

INTRODUCTION: Indocyanine green (ICG) elimination tests have been repeatedly suggested as an early predictor of graft function in patients with liver transplantation. Conventionally, ICG clearance (ClICG) is measured by a series of blood samples with subsequent laboratory analysis. More recently bedside techniques have become available to measure ICG concentrations in vivo and in addition to ClICG, the plasma disappearance rate of ICG (PDRICG) is increasingly being used. The aim of this study was to assess and to compare the normal time courses of ClICG and PDRICG in liver transplant recipients. METHODS: ClICG and PDRICG were measured perioperatively and at various times up to 24 h after liver transplantation. The bedside transpulmonary indicator dilution technique with an arterial fiberoptic-thermistor catheter was used to assess the ICG concentration time curve together with total circulating blood volume (Vd circ). RESULTS: Similar patterns of the time courses of ClICG and PDRICG with a fast recovery of ICG elimination in the early reperfusion period were observed. Compared to healthy subjects, ClICG was supranormal and PDRICG was slightly subnormal. In this study, Vd circ was increased at baseline and remained increased during surgery. CONCLUSIONS: PDRICG and ClICG are well suited to monitor onset and maintenance of graft function in patients undergoing liver transplantation. The PDRICG values measured tend to be relatively lower than ClICG because of an increased blood volume in these patients. By knowing these differences it is justified to monitor liver function in a very simple manner with PDRICG.

Plasma levels of macrophage migration inhibitory factor are elevated in patients with severe sepsis.

OBJECTIVE: To investigate the role of macrophage migration inhibitory factor (MIF) as a marker of severity of systemic inflammation in patients with severe sepsis and critically ill postsurgical patients. DESIGN: Prospective observational study in consecutive patients with severe sepsis, critically ill nonseptic postsurgical patients, and healthy blood donors. SETTING: A surgical intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: 19 patients with severe sepsis, 18 critically ill nonseptic postsurgical patients, and 10 healthy blood donors. MEASUREMENTS AND RESULTS: MIF plasma levels of patients and participants were measured. Interleukin 6 plasma levels were monitored as a control marker of inflammation. The median MIF plasma level was four to five times higher in patients with severe sepsis (2.70 ng/ml, range 0.31-19.59) and in critically ill nonseptic postsurgical patients (2.43 ng/ml, range 0.49-4.31) than in healthy blood donors (0.56 ng/ml, range 0.16-1.68). MIF plasma levels did not differ between the patient groups. CONCLUSIONS: MIF serves as a general marker for systemic inflammation in septic and nonseptic acute critical illness, but MIF does not discriminate for severity or differentiate between infectious and noninfectious origins of an acute critical illness.

Cardiorespiratory effects of automatic tube compensation during airway pressure release ventilation in patients with acute lung injury.

BACKGROUND: Spontaneous breaths during airway pressure release ventilation (APRV) have to overcome the resistance of the artificial airway. Automatic tube compensation provides ventilatory assistance by increasing airway pressure during inspiration and lowering airway pressure during expiration, thereby compensating for resistance of the artificial airway. The authors studied if APRV with automatic tube compensation reduces the inspiratory effort without compromising cardiovascular function, end-expiratory lung volume, and gas exchange in patients with acute lung injury. METHODS: Fourteen patients with acute lung injury were breathing spontaneously during APRV with or without automatic tube compensation in random order. Airway pressure, esophageal and abdominal pressure, and gas flow were continuously measured, and tracheal pressure was estimated. Transdiaphragmatic pressure time product was calculated. End-expiratory lung volume was determined by nitrogen washout. The validity of the tracheal pressure calculation was investigated in seven healthy ventilated pigs. RESULTS: Automatic tube compensation during APRV increased airway pressure amplitude from 7.7+/-1.9 to 11.3+/-3.1 cm H2O (mean +/- SD; P < 0.05) while decreasing trans-diaphragmatic pressure time product from 45+/-27 to 27+/-15 cm H2O x s(-1) x min(-1) (P < 0.05), whereas tracheal pressure amplitude remained essentially unchanged (10.3+/-3.5 vs. 10.1+/-3.5 cm H2O). Minute ventilation increased from 10.4+/-1.6 to 11.4+/-1.5 l/min (P < 0.001), decreasing arterial carbon dioxide tension from 52+/-9 to 47+/-6 mmHg (P < 0.05) without affecting arterial blood oxygenation or cardiovascular function. End-expiratory lung volume increased from 2,806+/-991 to 3,009+/-994 ml (P < 0.05). Analysis of tracheal pressure-time curves indicated nonideal regulation of the dynamic pressure support during automatic tube compensation as provided by a standard ventilator. CONCLUSION: In the studied patients with acute lung injury, automatic tube compensation markedly unloaded the inspiratory muscles and increased alveolar ventilation without compromising cardiorespiratory function and end-expiratory lung volume.

Long-term effects of spontaneous breathing during ventilatory support in patients with acute lung injury.

Improved gas exchange has been observed during spontaneous breathing with airway pressure release ventilation (APRV) as compared with controlled mechanical ventilation. This study was designed to determine whether use of APRV with spontaneous breathing as a primary ventilatory support modality better prevents deterioration of cardiopulmonary function than does initial controlled mechanical ventilation in patients at risk for acute respiratory distress syndrome (ARDS). Thirty patients with multiple trauma were randomly assigned to either breathe spontaneously with APRV (APRV Group) (n = 15) or to receive pressure-controlled, time-cycled mechanical ventilation (PCV) for 72 h followed by weaning with APRV (PCV Group) (n = 15). Patients maintained spontaneous breathing during APRV with continuous infusion of sufentanil and midazolam (Ramsay sedation score [RSS] of 3). Absence of spontaneous breathing (PCV Group) was induced with sufentanil and midazolam (RSS of 5) and neuromuscular blockade. Primary use of APRV was associated with increases (p < 0.05) in respiratory system compliance (CRS), arterial oxygen tension (PaO2), cardiac index (CI), and oxygen delivery (DO2), and with reductions (p < 0.05) in venous admixture (QVA/QT), and oxygen extraction. In contrast, patients who received 72 h of PCV had lower CRS, PaO2, CI, DO2, and Q VA/Q T values (p < 0.05) and required higher doses of sufentanil (p < 0.05), midazolam (p < 0.05), noradrenalin (p < 0.05), and dobutamine (p < 0.05). CRS, PaO2), CI and DO2 were lowest (p < 0.05) and Q VA/Q T was highest (p < 0.05) during PCV. Primary use of APRV was consistently associated with a shorter duration of ventilatory support (APRV Group: 15 +/- 2 d [mean +/- SEM]; PCV Group: 21 +/- 2 d) (p < 0.05) and length of intensive care unit (ICU) stay (APRV Group: 23 +/- 2 d; PCV Group: 30 +/- 2 d) (p < 0.05). These findings indicate that maintaining spontaneous breathing during APRV requires less sedation and improves cardiopulmonary function, presumably by recruiting nonventilated lung units, requiring a shorter duration of ventilatory support and ICU stay.

The effects of prone positioning on intraabdominal pressure and cardiovascular and renal function in patients with acute lung injury.

UNLABELLED: To detect any harmful effects of prone positioning on intraabdominal pressure (IAP) and cardiovascular and renal function, we studied 16 mechanically ventilated patients with acute lung injury randomly in prone and supine positions, without minimizing the restriction of the abdomen. Effective renal blood flow index and glomerular filtration rate index were determined by the paraaminohippurate and inulin clearance techniques. Prone positioning resulted in an increase in IAP from 12 +/- 4 to 14 +/- 5 mm Hg (P < 0.05), PaO(2)/fraction of inspired oxygen from 220 +/- 91 to 267 +/- 82 mm Hg (P < 0.05), cardiac index from 4.1 +/- 1.1 to 4.4 +/- 0.7 L/min (P < 0.05), mean arterial pressure from 77 +/- 10 to 82 +/- 11 mm Hg (P < 0.01), and oxygen delivery index from 600 +/- 156 to 648 +/- 95 mL. min(-)(1). m(-)(2) (P < 0.05). Renal fraction of cardiac output decreased from 19.1% +/- 12.5% to 15.5% +/- 8.8% (P < 0.05), and renal vascular resistance index increased from 11762 +/- 6554 dynes. s. cm(-)(5). m(2) to 15078 +/- 10594 dynes. s. cm(-)(5). m(2) (P < 0.05), whereas effective renal blood flow index, glomerular filtration rate index, filtration fraction, urine volume, fractional sodium excretion, and osmolar and free water clearances remained constant during prone positioning. Prone positioning, when used in patients with acute lung injury, although it is associated with a small increase in IAP, contributes to improved arterial oxygenation and systemic blood flow without affecting renal perfusion and function. Apparently, special support to allow free chest and abdominal movement seems unnecessary when mechanically ventilated, hemodynamically stable patients without abdominal hypertension are proned to improve gas exchange. IMPLICATIONS: Prone positioning is increasingly used to improve gas exchange in patients with acute lung injury. However, during prone positioning an increase in intraabdominal pressure in these critically ill patients may promote dysfunction of other organs. Therefore, we performed a randomized study in mechanically ventilated patients with acute lung injury to investigate the cardiovascular and renal effects of prone positioning.

The hypothalamic-pituitary-adrenal axis of patients with severe sepsis: altered response to corticotropin-releasing hormone.

OBJECTIVE: To investigate the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with severe sepsis by stimulating with corticotropin-releasing hormone (CRH). DESIGN: Prospective observational study in consecutive intensive care unit patients with severe sepsis. SETTING: Surgical intensive care unit and outpatient department of endocrinology in a university hospital. PATIENTS: The study included 20 patients with the diagnosis of severe sepsis; six critically ill, nonseptic patients after major surgery; ten patients with primary adrenal insufficiency; ten patients with anterior pituitary insufficiency; and ten individuals without clinical signs of HPA axis disturbance. INTERVENTIONS: CRH tests were performed with an intravenous bolus injection of 100 microg of human CRH. MEASUREMENTS AND MAIN RESULTS: We studied the functional integrity of the HPA axis in patients with severe sepsis by performing the CRH test. In addition, during the period of severe sepsis, we repeatedly measured basal plasma concentrations of adrenocorticotropin hormone (ACTH) and cortisol. The mean basal plasma cortisol concentration was decreased significantly in nonsurvivors with severe sepsis (288.8 +/- 29.1 [sem] nmol/L) compared with survivors (468.1+/- 18.6 nmol/L; p <.01). By calculating the ACTH/cortisol indices, we found no evidence for adrenal insufficiency in patients with severe sepsis. The mean ACTH/cortisol indices of nonsurvivors with severe sepsis (0.02 +/- 0.008) and survivors (0.01 +/- 0.002) were significantly lower compared with the index of patients with primary adrenal insufficiency (6.8 +/- 1.0; p <.001). In contrast, in nonsurvivors with severe sepsis, the plasma cortisol response to CRH stimulation was impaired compared with survivors: The mean basal cortisol concentration within the CRH test was 269.4 +/- 39.8 nmol/L in nonsurvivors compared with 470.8 +/- 48.4 nmol/L in survivors and increased to a peak value of 421.6 +/- 72.6 nmol/L in nonsurvivors and 680.7 +/- 43.8 nmol/L in survivors (p <.02). However, the change in plasma cortisol, expressed as mean +/- sem and calculated by subtracting the basal cortisol from the peak cortisol after CRH stimulation, was not significantly different in survivors with severe sepsis (243.5 +/- 36.1, range 111.0-524.0 nmol/L, n = 15) compared with nonsurvivors (161.0 +/- 38.9, range 42.0-245.0 nmol/L, n = 5; p >.05). CONCLUSIONS: We found lower basal plasma cortisol concentrations in nonsurvivors compared with survivors of severe sepsis. In addition, the plasma cortisol response to a single CRH stimulation was impaired in nonsurvivors compared with survivors. Reduced responses to CRH stimulation may reflect a state of endocrinologic organ dysfunction in severe sepsis.