M. Haller

Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study.

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.

Health-related quality of life and posttraumatic stress disorder in survivors of the acute respiratory distress syndrome

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.

Sensitivity and specificity of a screening test to document traumatic experiences and to diagnose post-traumatic stress disorder in ARDS patients after intensive care treatment.

Objective: Many survivors of critical illness and intensive care unit (ICU) treatment have traumatic memories such as nightmares, panic or pain which can be associated with the development of post-traumatic stress disorder (PTSD). In order to simplify the rapid and early detection of PTSD in such patients, we modified an existing questionnaire for diagnosis of PTSD and validated the instrument in a cohort of ARDS patients after long-term ICU therapy. Design: Follow-up cohort study. Setting: The 20-bed ICU of a university teaching hospital. Patients: A cohort of 52 long-term survivors of the acute respiratory distress syndrome (ARDS). Interventions and measurements: The questionnaire was administered to the study cohort at two time points 2 years apart. At the second evaluation, the patients underwent a structured interview with two trained psychiatrists to diagnose PTSD according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. The reliability and validity of the questionnaire was then estimated and its specificity, sensitivity and optimal decision threshold determined using receiver operating characteristic (ROC) curve analyses. Results: The questionnaire showed a high internal consistency (Crohnbachs α = 0.93) and a high test-retest reliability (intraclass correlation coefficient α = 0.89). There was evidence of construct validity by a linear relationship between scores and the number of traumatic memories from the ICU the patients described (Spearmans ϱ = 0.48,p < 0.01). Criterion validity was demonstrated by ROC curve analyses resulting in a sensitivity of 77.0 % and a specificity of 97.5 % for the diagnosis of PTSD. Conclusions: The questionnaire was found to be a responsive, valid and reliable instrument to screen survivors of intensive care for PTSD.

Changes in blood volume and hematocrit during acute preoperative volume loading with 5% albumin or 6% hetastarch solutions in patients before radical hysterectomy.

BackgroundThe impact of acute preoperative volume loading with colloids on blood volume has not been investigated sufficiently. MethodsBefore surgery, in 20 patients undergoing major gynecologic procedures, volume loading was performed during anesthesia by infusing approximately 20 ml/kg of colloid at a rate of 90 ml/min (group I: 5% albumin solution; group II: 6% hetastarch solution; n = 10 each). Plasma volume (indocyanine green dilution technique), erythrocyte volume (labeling erythrocytes with fluorescein), hematocrit, total protein, and hetastarch plasma concentrations (group II) were measured before and 30 min after the end of infusion. ResultsMore than 1,350 ml of colloid (approximately 50% of the baseline plasma volume) were infused within 15 min. Thirty minutes after the infusion had been completed, blood volume was only 524 ± 328 ml (group I) and 603 ± 314 ml (group II) higher than before volume loading. The large vessel hematocrit (measured by centrifugation) dropped more than the whole body hematocrit, which was derived from double-label measurements of blood volume. ConclusionsThe double-label measurements of blood volume performed showed that 30 min after the infusion of approximately 20 ml/kg of 5% albumin or 6% hetastarch solution (within 15 min), only mean 38 ± 21% and 43 ± 26%, respectively, of the volume applied remained in the intravascular space. Different, i.e., earlier or later, measuring points, different infusion volumes, infusion rates, plasma substitutes, or possibly different tracers for plasma volume measurement might lead to different results concerning the kinetics of fluid or colloid extravasation.

The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder and health-related quality of life in survivors.

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.

Evaluation of a new continuous thermodilution cardiac output monitor in cardiac surgical patients : A prospective criterion standard study

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.

Pulmonary function and health-related quality of life in a sample of long-term survivors of the acute respiratory distress syndrome

Objective: We performed a follow-up cohort analysis in order to delineate the correlation between pulmonary function (PF) and health-related quality of life (HRQL) in patients after ARDS.¶Design: Follow-up cohort study.¶Setting: A 20-bed ICU of a university teaching hospital.¶Patients: A cohort of 50 long-term survivors of ARDS.¶Measurements and results: Measurements of PF (FVC, FEV1, TLC, DLCO) and HRQL (SF-36 Health Status Questionnaire) were made 5.5 years (median value) after discharge from the ICU. Impairments in PF (defined as PF results below 80 % of the predicted value) were frequent but generally mild. Twenty patients had a single PF impairment (with limitations in FEV1/FVC ratio in 12 patients being the most common), four patients had two (with DLCO and FEV1/FVC ratio impairment the most common) and three patients had pathologic results in three PF tests (FEV1/FVC ratio, TLC and capillary pO2 during exercise in one case, FVC, TLC and capillary pO2 during exercise in the second patient and FVC, TLC and DLCO in the third). Compared to normal controls, survivors of ARDS showed impairments in all SF-36 health dimensions (p < 0.001). Patients with multiple (> 1) PF impairments described the lowest HRQL with major limitations in all SF-36 categories (p < 0.037) including physical and mental summary scores (36.5 vs 46.9, p = 0.037 and 31.3 vs 51.4, p = 0.003) when compared to patients with no or only one PF impairment.¶Conclusions: Long-term survivors of ARDS have a significant reduction in HRQL and the presence of multiple PF impairments is associated with maximal decrements in HRQL.

Beat-to-beat measurement of cardiac output by intravascular pulse contour analysis: A prospective criterion standard study in patients after cardiac surgery

OBJECTIVE To evaluate the accuracy of a new pulse contour method of measuring cardiac output in critically ill patients. DESIGN A prospective criterion standard study. SETTING Cardiac surgery intensive care unit in a university hospital. PARTICIPANTS Nineteen cardiac surgery patients requiring intensive care treatment with pulmonary artery catheters after surgery. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The pulse contour cardiac output monitor uses transpulmonary bolus thermodilution measurements to calibrate the system. In each patient, the pulse contour cardiac output values were compared with conventional thermodilution. The method described by Bland and Altman and linear regression analysis were used for comparison. The mean difference (bias) +/- standard deviation of differences (precision) was 0.31 +/- 1.25 L/min for pulmonary bolus thermodilution cardiac output versus pulse contour cardiac output and 0.21 +/- 0.73 L/min for pulmonary bolus thermodilution cardiac output versus transpulmonary bolus thermodilution cardiac output. Linear regression (correlation) analyses were pulse contour cardiac output = 0.97 thermodilution + 0.53 (r = 0.88), and transpulmonary cardiac output = 0.87 thermodilution + 1.09 (r = 0.96). There was a small increase 60 minutes after recalibration but not a statistically significant difference between pulse contour cardiac output and pulmonary bolus thermodilution cardiac output (p = 0.52). CONCLUSIONS Bias and precision are acceptable, and the system provides results that agree with conventional thermodilution. This study demonstrates the clinical applicability of the pulse contour cardiac output monitoring system.

Changes in intravascular volume during acute normovolemic hemodilution and intraoperative retransfusion in patients with radical hysterectomy.

Background: Changes in blood volume during acute normovolemic hemodilution (ANH) and their consequences for the perioperative period have not been investigated sufficiently. Methods: In 15 patients undergoing radical hysterectomy, preoperative ANH to a hematocrit of 24% was performed using 5% albumin solution. Intraoperatively, saline 0.9% solution was used for volume substitution, and intraoperative retransfusion was started at a hematocrit of 20%. Plasma volume (indocyanine green dilution technique), hematocrit, and plasma protein concentration were measured before and after ANH, before retransfusion, and postoperatively. Red cell volume (labeling erythrocytes with fluorescein) was determined before and after ANH and postoperatively. Results: Mean normal plasma volumes (1,514 ± 143 ml/m2) and reduced red cell volumes (707 ± 79 ml/m2) were measured preoperatively. Blood (1,150 ± 196 ml) was removed and replaced with 1,333 ± 204 ml of colloid. Blood volume before and after ANH was equal and amounted to 3,740 ml. Intraoperatively, plasma volume did not increase until retransfusion despite infusing 3,389 ± 1,021 ml of crystalloid (corrected for urine output) to compensate for an estimated surgical blood loss of 727 ± 726 ml. Postoperatively, after retransfusion of all autologous blood, blood volume was 255 ± 424 ml higher than preoperatively before ANH. Despite mean calculated blood loss of 1,256 ± 892 ml, only one patient received allogeneic blood. Conclusions: During ANH, normovolemia was exactly maintained. After surgical blood loss of 1,256 ± 892 ml, crystalloid and colloid supplies of 5,752 ± 1,462 ml and 1,667 ± 548 ml, respectively, and complete intraoperative retransfusions of autologous blood in every patient, mean blood volume was 250 ml higher than preoperatively before ANH.

Effects of noninvasive positive pressure ventilatory support in non-COPD patients with acute respiratory insufficiency after early extubation.

Objective: To investigate the effects of noninvasive positive pressure ventilation (NPPV) on pulmonary gas exchange, breathing pattern, intrapulmonary shunt fraction, oxygen consumption, and resting energy expenditure in patients with persistent acute respiratory failure but without chronic obstructive pulmonary disease (COPD) after early extubation. Design: Prospective study. Setting: Multidisciplinary intensive care unit of a university hospital. Patients: 15 patients after prolonged mechanical ventilation (> 72 h) with acute respiratory insufficiency after early extubation. Interventions: Criteria for early extubation were arterial oxygen tension (PaO2) L 40 mm Hg (fractional inspired oxygen 0.21), arterial carbon dioxide tension (PaCO2) K 55 mm Hg, pH > 7.32, respiratory rate K 40 breaths per min, tidal volume (VT) L 3 ml/kg, rapid shallow breathing index K 190 and negative inspiratory force L 20 cmH2O. After extubation, two modes of NPPV were applied [continuous positive airway pressure (CPAP) of 5 cmH2O and pressure support ventilation (PSV) with 15 cmH2O pressure support]. Measurements and main results: Oxygenation and ventilatory parameters improved during both modes of NPPV (p < 0.05): increase in PaO2 of 11 mm Hg during CPAP and 21 mm Hg during PSV; decrease in intrapulmonary shunt fraction of 7 % during CPAP and 12 % during PSV; increase in tidal volume of 1 ml/kg during CPAP and 4 ml/kg during PSV; decrease in respiratory rate 6 breaths/min during CPAP and 9 breaths/min during PSV. Oxygen consumption (15 % during CPAP, 22 % during PSV) and resting energy expenditure (12 % during CPAP, 20 % during PSV) were reduced (p < 0.05). PaCO2 decreased, whereas minute ventilation and pH increased during PSV (p < 0.05). The median duration of NPPV was 2 days. Two patients had to be reintubated. Conclusions: In non-COPD patients with persistent acute respiratory failure after early extubation, NPPV improved pulmonary gas exchange and breathing pattern, decreased intrapulmonary shunt fraction, and reduced the work of breathing.