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Objective: To provide a narrative review of the latest concepts and understanding of the pathophysiology of critical illness-related corticosteroid insufficiency (CIRCI)., Participants: A multi-specialty task force of international experts in critical care medicine and endocrinology and members of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine., Data Sources: Medline, Database of Abstracts of Reviews of Effects (DARE), Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews., Results: Three major pathophysiologic events were considered to constitute CIRCI: dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, altered cortisol metabolism, and tissue resistance to glucocorticoids. The dysregulation of the HPA axis is complex, involving multidirectional crosstalk between the CRH/ACTH pathways, autonomic nervous system, vasopressinergic system, and immune system. Recent studies have demonstrated that plasma clearance of cortisol is markedly reduced during critical illness, explained by suppressed expression and activity of the primary cortisol-metabolizing enzymes in the liver and kidney. Despite the elevated cortisol levels during critical illness, tissue resistance to glucocorticoids is believed to occur due to insufficient glucocorticoid alpha-mediated anti-inflammatory activity., Conclusions: Novel insights into the pathophysiology of CIRCI add to the limitations of the current diagnostic tools to identify at-risk patients and may also impact how corticosteroids are used in patients with CIRCI.

Objective: To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients., Participants: A multispecialty task force of 16 international experts in critical care medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine., Design/methods: The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of at least 80% of the task force members., Results: The task force was unable to reach agreement on a single test that can reliably diagnose CIRCI, although delta cortisol (change in baseline cortisol at 60 min of < 9 μg/dL) after cosyntropin (250 μg) administration and a random plasma cortisol of < 10 μg/dL may be used by clinicians. We suggest against using plasma-free cortisol or salivary cortisol level over plasma total cortisol (conditional, very low quality of evidence). For treatment of specific conditions, we suggest using IV hydrocortisone < 400 mg/day for ≥ 3 days at full dose in patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy (conditional, low quality of evidence). We suggest not using corticosteroids in adult patients with sepsis without shock (conditional recommendation, moderate quality of evidence). We suggest the use of IV methylprednisolone 1 mg/kg/day in patients with early moderate to severe acute respiratory distress syndrome (PaO2/FiO2 < 200 and within 14 days of onset) (conditional, moderate quality of evidence). Corticosteroids are not suggested for patients with major trauma (conditional, low quality of evidence)., Conclusions: Evidence-based recommendations for the use of corticosteroids in critically ill patients with sepsis and septic shock, acute respiratory distress syndrome, and major trauma have been developed by a multispecialty task force.

Objective: Acquired glucocorticoid resistance frequently complicates the therapy of sepsis. It leads to an exaggerated proinflammatory response and has been related to altered expression profiles of glucocorticoid receptor isoforms glucocorticoid receptor-α (mediating anti-inflammatory effects) and glucocorticoid receptor-β (acting as a dominant negative inhibitor). We investigated the impact of glucocorticoid receptor isoforms on glucocorticoid effects in human T-cells. We hypothesized that 1) changes of the ratio of glucocorticoid receptor isoforms impact glucocorticoid resistance and 2) glucocorticoid receptor-α expression is controlled by microRNA-mediated gene silencing., Design: Laboratory-based study., Setting: University research laboratory., Subjects and Patients: Healthy volunteers, sepsis patients., Methods: First, T-cells from healthy volunteers (native and CD3/CD28-stimulated cells with or without addition of hydrocortisone) were analyzed for the expression of glucocorticoid receptor-isoforms by quantitative polymerase chain reaction. Additionally, effects of gene silencing of glucocorticoid receptor-β by siRNA transfection were determined. Secondly, microRNA-mediated silencing was evaluated by cloning of a glucocorticoid receptor-α-specific 3'-untranslated-region reporter construct and subsequent transfection experiments in cell cultures. Effects of miRNA transfection on glucocorticoid receptor-α expression were analyzed in Jurkat T-cells and in T-cells from healthy volunteers (quantitative polymerase chain reaction and Western blotting). Finally, expression of glucocorticoid receptor-α, glucocorticoid receptor-β, and miR-124 was tested in T-cells of sepsis patients (n=24)., Measurements and Main Results: Stimulation of T-cells induced a significant upregulation of glucocorticoid receptor-α (not glucocorticoid receptor-β) thereby possibly rendering T-cells more sensitive to glucocorticoids; this T-cell response was hindered by hydrocortisone. Silencing of glucocorticoid receptor-β doubled the inhibitory effects of glucocorticoids on interleukin-2 production. MicroRNA-124 was proved to specifically downregulate glucocorticoid receptor-α. Furthermore, a glucocorticoid-induced three-fold upregulation of microRNA-124 was found. T-cells of sepsis patients exhibited slightly decreased glucocorticoid receptor-α and slightly increased miR-124 expression levels, whereas glucocorticoid receptor-β expression was two-fold upregulated (p<.01) and exhibited a remarkable interindividual variability., Conclusions: Glucocorticoid treatment induces expression of miR-124, which downregulates glucocorticoid receptor-α thereby limiting anti-inflammatory effects of glucocorticoids. Steroid treatment might aggravate glucocorticoid resistance in patients with high glucocorticoid receptor-β levels.

Objective: Glucocorticoids play a major role in the consolidation and retrieval of traumatic information. They act through the glucocorticoid receptor, for which, in humans, several polymorphisms have been described. In particular, the BclI single-nucleotide polymorphism is associated with hypersensitivity to glucocorticoids and with susceptibility to development of major depression. Furthermore, in patients with posttraumatic stress disorder carrying the BclI GG genotype, cortisol levels were lower and showed an inverse relationship to posttraumatic stress disorder symptom intensity. Here, we studied the association of the BclI polymorphism with plasma cortisol levels, traumatic memories, posttraumatic stress disorder symptoms, and health-related quality of life outcomes in 126 patients undergoing cardiac surgery and intensive care unit therapy., Design: Prospective observational study., Setting: Cardiovascular intensive care unit in a university hospital., Patients: A total of 126 patients undergoing cardiac surgery and intensive care unit treatment., Interventions: No interventions were performed., Measurements and Main Results: Validated questionnaires were used to quantify end points. Measurements were taken 1 day before and 1 wk and 6 months after cardiac surgery. Homozygous carriers of the BclI G allele (n = 21) had significantly lower preoperative plasma cortisol levels and more long-term traumatic memories from intensive care unit therapy at 6 months after cardiac surgery than heterozygous carriers or noncarriers (1.9 ± 1.4 vs. 1.0 ± 1.2, p = .01). Anxiety was significantly more common as a long-term traumatic memory in homozygous BclI G allele carriers than in heterozygous carriers or noncarriers (57% vs. 35%, p = .03). Posttraumatic stress disorder symptom scores were significantly higher at discharge from the intensive care unit in homozygous BclI G allele carriers than in heterozygous carriers or noncarriers. Only heterozygous carriers or BclI G allele noncarriers had a significant gain in health-related quality of life physical function at 6 months after cardiac surgery (p < .01). Baseline values were not statistically different between carriers of the different BclI alleles., Conclusion: Homozygous BclI G allele carriers are at risk for traumatic memories, posttraumatic stress disorder symptoms, and lower health-related quality of life after cardiac surgery and intensive care unit therapy. The BclI single-nucleotide polymorphism may help to identify individuals at need for tailored medical care.

Background: Severe systemic inflammation (systemic inflammatory response syndrome) associated with cardiac surgery often leads to a worse short-term and long-term outcome. Stress doses of hydrocortisone have been successfully used to improve outcome of CS. The interleukin (IL)-6 to IL-10 ratio is associated with outcome after trauma and major surgery., Objective: To evaluate immunologic effects (especially IL-6 to IL-10 ratio) of stress doses of hydrocortisone in a high-risk group of patients after cardiac surgery with cardiopulmonary bypass., Design: Prospective, randomized, double-blinded, placebo-controlled trial., Setting: Cardiovascular intensive care unit of a university hospital., Patients: High-risk patients (n = 36) undergoing CS., Intervention: Stress doses of hydrocortisone or placebo., Main Outcome Measures: IL-6 to IL-10 ratio and other markers of systemic inflammation at predefined time points; short-term clinical outcome., Results: The two study groups did not differ with regard to demographic data. The patients from the hydrocortisone group (n = 19) had significantly lower levels of IL-6 and higher levels of IL-10, resulting in an attenuated change in IL-6/IL-10 ratio (28.7 [6.4/128.7] vs. 292.8 [6.5/534.6] 4 hours after cardiopulmonary bypass; p < 0.001). Patients in the hydrocortisone group had a shorter duration of catecholamine support (1 [1/2] vs. 4 [2/4.5] days; p = 0.02), a shorter length of stay in the intensive care unit (2 [2/3] vs. 6 [4/8] days; p = 0.001), and a lower incidence of postoperative atrial fibrillation (26% vs. 59%; p = 0.04)., Conclusions: Stress doses of hydrocortisone attenuate the evolution of IL-6/IL-10 ratio in patients with systemic inflammatory response syndrome after CS, which seems to be associated with an improved outcome. The immunologic effects of hydrocortisone may thus be both, inhibitory (IL-6) and permissive (IL-10), regarding the immune response.

Objective: To develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients., Participants: A multidisciplinary, multispecialty task force of experts in critical care medicine was convened from the membership of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. In addition, international experts in endocrinology were invited to participate., Design/methods: The task force members reviewed published literature and provided expert opinion from which the consensus was derived. The consensus statements were developed using a modified Delphi methodology. The strength of each recommendation was quantified using the Modified GRADE system, which classifies recommendations as strong (grade 1) or weak (grade 2) and the quality of evidence as high (grade A), moderate (grade B), or low (grade C) based on factors that include the study design, the consistency of the results, and the directness of the evidence., Results: The task force coined the term critical illness-related corticosteroid insufficiency to describe the dysfunction of the hypothalamic-pituitary-adrenal axis that occurs during critical illness. Critical illness-related corticosteroid insufficiency is caused by adrenal insufficiency together with tissue corticosteroid resistance and is characterized by an exaggerated and protracted proinflammatory response. Critical illness-related corticosteroid insufficiency should be suspected in hypotensive patients who have responded poorly to fluids and vasopressor agents, particularly in the setting of sepsis. At this time, the diagnosis of tissue corticosteroid resistance remains problematic. Adrenal insufficiency in critically ill patients is best made by a delta total serum cortisol of < 9 microg/dL after adrenocorticotrophic hormone (250 microg) administration or a random total cortisol of < 10 microg/dL. The benefit of treatment with glucocorticoids at this time seems to be limited to patients with vasopressor-dependent septic shock and patients with early severe acute respiratory distress syndrome (PaO2/FiO2 of < 200 and within 14 days of onset). The adrenocorticotrophic hormone stimulation test should not be used to identify those patients with septic shock or acute respiratory distress syndrome who should receive glucocorticoids. Hydrocortisone in a dose of 200 mg/day in four divided doses or as a continuous infusion in a dose of 240 mg/day (10 mg/hr) for > or = 7 days is recommended for septic shock. Methylprednisolone in a dose of 1 mg x kg(-1) x day(-1) for > or = 14 days is recommended in patients with severe early acute respiratory distress syndrome. Glucocorticoids should be weaned and not stopped abruptly. Reinstitution of treatment should be considered with recurrence of signs of sepsis, hypotension, or worsening oxygenation. Dexamethasone is not recommended to treat critical illness-related corticosteroid insufficiency. The role of glucocorticoids in the management of patients with community-acquired pneumonia, liver failure, pancreatitis, those undergoing cardiac surgery, and other groups of critically ill patients requires further investigation., Conclusion: Evidence-linked consensus statements with regard to the diagnosis and management of corticosteroid deficiency in critically ill patients have been developed by a multidisciplinary, multispecialty task force.

Objective: Severe systemic inflammation with a vasodilatory syndrome occurs in about one third of all patients after cardiac surgery with cardiopulmonary bypass. Hydrocortisone has been used successfully to reverse vasodilation in septic patients. We evaluated if stress doses of hydrocortisone attenuate severe systemic inflammatory response syndrome in a predefined risk group of patients after cardiac surgery with cardiopulmonary bypass., Design: Randomized, nonblinded, controlled trial., Setting: Anesthesiologic intensive care unit for cardiac surgical patients of an university hospital., Patients: After a risk analysis, we enrolled 91 patients into a prospective randomized trial. Patients were included according to the evaluated criteria (preoperative ejection fraction, duration of cardiopulmonary bypass, type of surgery)., Interventions: The treatment group received stress doses of hydrocortisone perioperatively: 100 mg before induction of anesthesia, then 10 mg/hr for 24 hrs, 5 mg/hr for 24 hrs, 3 x 20 mg/day, and 3 x 10 mg/day., Measurements and Main Results: We measured various laboratory (e.g., lactate) and clinical variables (e.g., duration of ventilation and length of stay in the intensive care unit), characterizing the patients' outcome. The two study groups did not differ regarding age, preoperative medication, duration of the cardiopulmonary bypass, and type of surgery. The patients in the treatment group had significantly lower concentrations of IL-6 and lactate, higher antithrombin III concentration, lower need for circulatory and ventilatory support and for transfusions, lower Therapeutic Intervention Scoring System values, and shorter length of stay in the intensive care unit and in the hospital. The mortality rate did not differ significantly between the groups., Conclusions: Although we acknowledge the limitations of a nonblinded interventional trial, stress doses of hydrocortisone seem to attenuate systemic inflammation in a predefined risk group of patients after cardiac surgery with cardiopulmonary bypass and improve early outcome.

Objectives: The exposure to intense physical and psychological stress during intensive care can result in posttraumatic stress disorder (PTSD) in survivors. Cortisol is a biological stress mediator that can have a protective effect during severe stress. The administration of stress doses of hydrocortisone during treatment in the intensive care unit could theoretically result in a lower incidence of PTSD. We tested this hypothesis in survivors of septic shock., Design: A retrospective case-controlled analysis., Setting: A 20-bed multidisciplinary intensive care unit of a tertiary-care university hospital., Patients: We identified 27 patients who received standard therapy for septic shock. These patients served as controls and were compared with an equal number of patients who received hydrocortisone in addition to standard treatment. These patients were selected from our database with regard to age (+/-4 yrs), gender, and cause of septic shock to be as similar as possible with control patients., Interventions: Patients from the hydrocortisone group had received stress doses of hydrocortisone (100 mg bolus, followed by 0.18 mg/kg/hr) in addition to standard treatment. Patients from the control group received standard protocol-driven treatment only. PTSD was diagnosed with the Posttraumatic Stress Syndrome-10 inventory, a self-report scale for diagnosis of PTSD. Health-related quality of life was measured using the Medical Outcomes Study Short-Form Survey (Medical Outcomes Trust, Boston, MA), which consists of 36 questions., Measurements and Main Results: Patients who received hydrocortisone during septic shock had a significantly lower incidence of PTSD than patients who received standard treatment only (5 of 27 vs. 16 of 27; p = .01) and had significantly higher scores on the mental health index of the Medical Outcomes Study Short-Form health-related quality-of-life questionnaire (68 vs. 44 points; p = .009)., Conclusions: Data from this study support the hypothesis that the administration of stress doses of hydrocortisone in doses equivalent to the maximal endocrine secretion rate during septic shock reduces the incidence of PTSD and improves emotional well-being in survivors. This hypothesis should be tested in a prospective randomized trial.

Objective: To investigate the effects of recombinant human growth hormone (rHGH) as a "rescue treatment" in an end-stage chronic obstructive pulmonary disease patient after prolonged weaning failure., Design: Descriptive case report., Setting: Fifteen-bed intensive care unit in a university hospital., Patient: A 62-year-old man with end-stage chronic obstructive pulmonary disease and pulmonary emphysema after lung reduction surgery and prolonged weaning failure after long-term mechanical ventilation., Interventions: After 42 days of unsuccessful weaning from the respirator, rHGH (27 IU/day, 0.3 IU/kg body weight/day) was administered for 20 days through a subcutaneous injection in addition to standard intensive care., Measurements and Main Results: In addition to daily routine laboratory studies, the visceral proteins prealbumin, retinol-binding protein, and transferrin, and nitrogen balance were measured twice a week, as were the thyroid hormones triiodothyronine, thyroxine, and thyroid-stimulating hormone, plasma insulin levels, and the insulin-like growth factor (IGF)-1 binding proteins IGF-BP1 and IGF-BP3. IGF-1 was measured from day 1 to day 4 of rHGH administration. Nutritional support was guided by indirect calorimetry. Additionally, weaning variables such as peak expiratory flow rate and expiratory tidal volume were measured noninvasively. T-piece weaning trials were carried out daily until respiratory muscle fatigue occurred. IGF-1 increased in response to rHGH stimulation, from 103 to 230 microg/mL, within 4 days. The carrier protein IGF-BP3 increased from 126 to 283 mg/L at the end of the study period, and the inhibiting IGF-BP1 decreased initially from 19 to 14 mg/L and then increased until the end of the study to 31 mg/L. Nitrogen balance increased initially from 4.6 to 13.6 g/24 hrs and thereafter decreased until the end of rHGH treatment to 8.3 g/24 hrs. Resting energy expenditure increased from 1800 to 2300 kcal/24 hrs. Peak expiratory flow rate increased from 0.69 to 0.88 L/sec. The expiratory tidal volume showed a slight increase during the study period during the daily decrease of pressure support on the ventilator setting. Respiratory muscular strength increased beginning 10 days after rHGH therapy was started. From this point, T-piece weaning trials could be prolonged almost daily. The patient was extubated successfully on postoperative day 75., Conclusions: This case report shows that after a prolonged catabolic state and long-term mechanical ventilation, administration of rHGH not only enhances the response of protein metabolism but improves respiratory muscular strength. Therefore, it may reduce the duration of mechanical ventilation in selected patients.

Objective: To investigate the effects of stress doses of hydrocortisone on the duration of vasopressor therapy in human septic shock., Design: Prospective, randomized, double-blind, single-center study., Setting: Twenty-bed multidisciplinary intensive care unit in a 1400-bed university hospital., Patients: Forty consecutive patients who met the ACCP/SCCM criteria for septic shock. An additional criterion for inclusion in the study was vasopressor support and high-output circulatory failure with a cardiac index of >4 L/min/m2 after fluid resuscitation (pulmonary capillary wedge pressure: 12-15 mm Hg) and without the use of positive inotropes such as dobutamine or dopexamine. The primary study end point was the time to cessation of vasopressor support (norepinephrine or epinephrine in any dose, dopamine > or = 6 microg/kg/min). Secondary study end points were the evolution of hemodynamics and the multiple organ dysfunction syndrome (MODS). The severity of illness at recruitment was graded using the Acute Physiology and Chronic Health Evaluation II and the Simplified Acute Physiology Score II scoring systems. MODS was described by the Sepsis-related Organ Failure Assessment score., Interventions: All eligible patients were prospectively randomized to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started with a loading dose of 100 mg given within 30 mins and followed by a continuous infusion of 0.18 mg/ kg/hr. When septic shock had been reversed, the dose of hydrocortisone was reduced to 0.08 mg/kg/hr. This dose was kept constant for 6 days. As soon as the underlying infection had been treated successfully or sodium serum concentrations had increased to >155 mmol/L, the hydrocortisone infusion was tapered in steps of 24 mg/day. Physiologic saline solution was the placebo., Measurements and Main Results: Hemodynamic and oxygen-derived variables were measured at previously defined time points over a study period of 5 days. Relevant clinical and laboratory measurements were registered for a study period of 14 days to assess the evolution of organ dysfunction. Baseline data at recruitment did not differ between the two groups. Shock reversal was achieved in 18 of the 20 patients treated with hydrocortisone vs. 16 of the 20 patients treated with placebo. Hydrocortisone significantly reduced the time to cessation of vasopressor support. The median time of vasopressor support was 2 days (1st and 3rd Quartiles, 1 and 6 days) in the hydrocortisone-treated group and 7 days (1st and 3rd Quartiles, 3 and 19 days) in the placebo group (p = .005 Breslow test). There was a trend to earlier resolution of the organ dysfunction syndrome in the hydrocortisone group., Conclusions: Infusion of stress doses of hydrocortisone reduced the time to cessation of vasopressor therapy in human septic shock. This was associated with a trend to earlier resolution of sepsis-induced organ dysfunctions. Overall shock reversal and mortality were not significantly different between the groups in this low-sized single-center study.

Objective: To evaluate the accuracy of a new continuous cardiac output monitor in critically ill patients., Design: Criterion standard study., Setting: Cardiac surgery intensive care unit in a university hospital., Patients: Twenty cardiac surgical patients requiring intensive care treatment with pulmonary artery catheters after surgery., Interventions: None., Measurements and Main Results: Cardiac output was monitored continuously with a modified pulmonary artery catheter that has a heating filament on the outside of the catheter. Four modes of data processing with different response times ("Normal," "Fast," "FastFilter," and "Urgent" modes) used by the monitoring system. A total of 240 determinations of cardiac output were performed using conventional bolus thermodilution technique; these results were compared with those obtained using three of the four continuous measuring modes available ("Normal," "FastFilter," and "Urgent"). Cardiac output ranged from 3.47 to 15.77 L/min (bolus thermodilution). The mean (bias) +/- SD of differences (precision) for all measurements was 0.40+/-1.26 L/min in the Normal mode (cardiac output <10 L/min: 0.34+/-0.66 L/min), 0.53+/-1.27 L/min in the FastFilter-mode (cardiac output <10 L/min: 0.60+/-0.75 L/min), and 0.63+/-1.34 L/min in the Urgent mode (cardiac output <10 L/min: 0.57+/-0.82 L/min)., Conclusions: Continuous cardiac output measurement using the thermodilution technique is reasonably accurate, reliable, and applicable in routine clinical practice. The values obtained using the Normal mode of the monitor agreed significantly better with the conventional thermodilution method than the results of the two other modes studied (FastFilter and Urgent). In addition, measurements in two patients with cardiac output values of >10 L/min did not agree with the results of the bolus thermodilution method.

Objectives: Despite considerable progress in intensive care management of the acute respiratory distress syndrome (ARDS), little is known about health-related quality of life in long-term survivors. In addition, intensive care treatment can be extremely stressful, and many survivors of ARDS report adverse experiences such as respiratory distress, anxiety, or pain during intensive care unit (ICU) treatment. This study was performed to assess health-related quality of life in survivors of ARDS and to test the hypothesis that adverse experiences during ICU treatment result in posttraumatic stress disorder (PTSD) and negative effects on health-related quality of life., Design: Retrospective, cohort, case-controlled analyses., Setting: A 12-bed multidisciplinary ICU of a tertiary care university hospital, capable of providing extracorporeal life support for adults with severe ARDS., Patients: We studied 80 patients who were admitted to our hospital from 1985 to 1995 and who survived an episode of ARDS. ARDS was defined according to the criteria of the American-European Consensus Conference on ARDS., Interventions: Health-related quality of life was measured using the Health Status Questionnaire of the self-administered Medical Outcomes Study Short Form Survey that consists of 36 questions (SF-36) and the German version of the Post Traumatic Stress Syndrome 10-Questions Inventory (PTSS-10), a self-report scale for the diagnosis of posttraumatic stress disorder based on the Diagnostic and Statistical Manual (Third Edition) criteria (American Psychiatric Association). The number of adverse experiences (anxiety, respiratory distress, pain, and nightmares) during intensive care was evaluated by means of a structured questionnaire. For each patient with ARDS, three age- and gender-comparable controls were randomly selected from databases providing normal values for the SF-36 and PTSS-10 scores in populations at risk for posttraumatic stress disorder., Measurements and Main Results: Survivors of ARDS showed statistically significant impairments in all eight health dimensions of the SF-36 when compared with normal controls (median reduction 21.3%, p < .006) with maximal impairments in physical function (median reduction 28.9%, p = .000) and a 38% higher frequency of chronic pain (p = .0001). Three of 34 patients reporting none, or one, adverse experience had evidence of posttraumatic stress disorder vs. 19 of 46 patients remembering multiple traumatic episodes (p = .007). Patients reporting multiple adverse experiences described the lowest health-related quality of life, with maximal impairments in psychosocial functioning (p < .005) and only small limitations in physical function., Conclusions: Long-term survivors of ARDS describe a good overall health-related quality of life. Major impairments in mental health domains of health-related quality of life are associated with the development of posttraumatic stress disorder and are a possible result of traumatic experiences during ICU therapy.

Objective: To evaluate the accuracy of a new continuous cardiac output monitor (one based on the thermodilution principle) in critically ill patients., Design: Criterion standard study., Setting: Multidisciplinary intensive care unit in a university hospital., Patients: Fourteen critically ill patients, with different diseases, requiring pulmonary artery catheterization., Interventions: In two patients with a left ventricular assist system, a defined, sudden 1 L/min change in cardiac output was carried through to evaluate the in vivo response time of the continuous cardiac output monitoring system. In the remaining 12 patients, cardiac output was altered by varying the dose of catecholamines, by volume loading, or by varying the level of sedation. In four patients, a rapid infusion of cold saline was given through a central venous catheter to test the performance of the system under these conditions., Measurements and Main Results: Cardiac output was monitored continuously. A total of 163 (13 to 18 per patient) bolus determinations of cardiac output were performed, using the conventional thermodilution technique and simultaneously using the indocyanine green dye dilution technique. The range of cardiac output was 3.8 to 15.6 L/min. The results of the continuous thermodilution method were compared with the results of the bolus thermodilution and the dye dilution methods, respectively. The mean difference (bias) +/- SD of differences (precision) was 0.35 +/- 1.01 L/min for continuous vs. bolus thermodilution and 0.34 +/- 1.01 L/min for continuous thermodilution vs. indocyanine green dye dilution. Linear regression (correlation) analyses were y = 0.95x + 0.76 (r2 = .91) for continuous and bolus thermodilution and y = 0.93x + 0.87 (r2 = .91) for continuous thermodilution and dye dilution. The 75% in vivo response time was 10.5 mins. The infusion of cold isotonic saline led to erroneous continuous cardiac output values. When the conventional bolus thermodilution and dye dilution techniques were compared, mean difference was -0.01 +/- 0.54 L/min and the results of linear regression analyses were y = 0.97x + 0.22 (r2 = .97)., Conclusions: Continuous cardiac output measurement using the thermodilution technique is reasonably accurate and is reliable and applicable in routine clinical practice, and therefore may add to patient safety. However, the response time is too slow for the immediate detection of acute changes in cardiac output. Some clinical conditions such as the rapid infusion of cold solutions can interfere with the continuous cardiac output measurement. Conventional bolus thermodilution and indocyanine green dye dilution methods showed good agreement and can be used interchangeably.

Objective: To evaluate the routine clinical performance of a new intra-arterial fiberoptic blood gas sensor that provides continuous PO2, PCO2, and pH monitoring., Design: Criterion standard study under routine clinical conditions., Setting: Intensive care unit (ICU) in a university hospital., Patients: Twenty-two sensors were tested in 13 patients with acute respiratory failure, including two patients receiving veno-venous extracorporeal lung assist. Patient selection was based on the necessity of frequent blood gas monitoring., Measurements: Sensor-deprived PO2, PCO2, and pH values were compared with values obtained using two different conventional laboratory blood gas analyzers located in the ICU. The median study period was 72 hrs per sensor (range 8 to 170 hrs). The quality of blood pressure readings with the sensor introduced through the arterial catheter was assessed by a grading system., Results: Mean differences between sensor-derived values and the average values of the two conventional blood gas analyzers were as follows: PO2 -2.4 +/- 6.5 (SD) torr (-0.3 +/- 0.9 kPa), PCO2 -2.9 +/- 3.9 torr (-0.4 +/- 0.5 kPa), and pH -0.04 +/- 0.03. Correlation coefficients were 0.99 (PO2), 0.94 (PCO2), and 0.89 (pH), respectively. The agreement between the two methods for PO2 measurement was better for the clinically important range of values (PO2 < 150 torr [< 20 kPa]) than for all measured PO2 values (range 30 to 522 torr [4 to 69.6 kPa]). Blood withdrawal and pressure readings were not adversely affected by the sensor. No side effects due to the insertion of the sensor were observed., Conclusions: The degree of agreement of intra-arterial blood gas sensor values with conventional blood gas analysis is within an acceptable range for routine clinical purposes. Acute changes in measured values are detected reliably. Continuous intra-arterial blood gas analysis can add substantially to the safety of patients with acute respiratory failure and can reduce blood sampling requirements for blood gas analysis.