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Objectives: Nonpharmacologic delirium management is recommended by current guidelines, but studies on the impact of ICU design are still limited. The study's primary purpose was to determine if a multicomponent change in room design prevents ICU delirium. Second, the influence of lighting conditions on serum melatonin was assessed., Design: Prospective observational cohort pilot study., Setting: The new design concept was established in two two-bed ICU rooms of a university hospital. Besides modifications aimed at stress relief, it includes a new dynamic lighting system., Patients: Seventy-four adult critically ill patients on mechanical ventilation with an expected ICU length of stay of at least 48 hours, treated in modified or standard rooms., Interventions: None., Measurements and Main Results: The clinical examination included a prospective assessment for depth of sedation, delirium, and pain every 8 hours using validated scores. Blood samples for serum melatonin profiles were collected every 4 hours for a maximum of three 24-hour periods. Seventy-four patients were included in the analysis. Seventy-six percent ( n = 28) of patients in the standard rooms developed delirium compared with 46% of patients ( n = 17) in the modified rooms ( p = 0.017). Patients in standard rooms (vs. modified rooms) had a 2.3-fold higher delirium severity (odds ratio = 2.292; 95% CI, 1.582-3.321; p < 0.0001). Light intensity, calculated using the measure of circadian effective irradiance, significantly influenced the course of serum melatonin ( p < 0.0001). Significant interactions ( p < 0.001) revealed that differences in serum melatonin between patients in standard and modified rooms were not the same over time but varied in specific periods of time., Conclusions: Modifications in ICU room design may influence the incidence and severity of delirium. Dedicated light therapy could potentially influence delirium outcomes by modulating circadian melatonin levels., Competing Interests: Dr. Luetz received funding from the Berlin Institute of Health Charité Clinician Scientist Program for conducting this study. Dr. Spies reports grants from the German Research Society, the German Aerospace Center, the Einstein Foundation Berlin, the Federal Joint Committee (G-BA), the Project Management Agency, the Non-Profit Society Promoting Science an Education, the European Society of Anaesthesiology and Intensive Care, Baxter Deutschland GmbH, Cytosorbents Europe GmbH, Edwards Lifesciences Germany GmbH, Fresenius Medical Care, Grünenthal GmbH, Masimo Europe Ltd., Pfizer Pharma PFE GmbH, Georg Thieme Verlag, Dr. F. Köhler Chemie GmbH, Sintetica GmbH, Philips Healthcare, Stiftung Charité, AGUETT ANT Deutschland GmbH, AbbVie Deutschland GmbH and KG, Amomed Pharma GmbH, lnTouch Health, Copra System GmbH, Correvio GmbH, Drägerwerk AG KGaA, the Max-Planck-Gesellschaft zur Förderung der Experiencing the risk of overutilizing opioids among patients with non-tumor chronic pain in ambulant care (ERONA) 2019–2021 Wissenschaften e.V., the Deutsche Gesellschaft für Anästhesiologie and lntensivmedizin and the Federal Ministry of Education and Research, outside the submitted work. Dr. Spies’ institution received funding from the Federal Ministry. Dr. Willemeit reports consulting fees from Trockland, Mercedes Benz, GSG Development, Hines Interests Limited Partnership and Signa Holding GmbH Development, outside the submitted work. Dr. Willemeit reports financial relationships with GRAFT Gesellschaft von Architekten mbH, GRAFT Designhaus GmbH and Graft GbR. Dr. Willemeit’s institution received funding from the German Ministry for Economic Research Funding (number KF2882602KJ2) and Charité Campus Virchow-Klinikum, Charité Facility Management; they disclosed relationships with Lighting Consultants LichtKunstLicht, Philips Lighting, and Art&Com; they received support for article research from the German Ministry for Economics Research Funding (number KF2882602KJ2). Dr. Luetz reports personal fees from Avanos Medical, Drägerwerk AG KGaA, Dr. Franz Köhler Chemie GmbH, Hill-Rom Holdings and Philips Healthcare outside the submitted work. He reports a grant from Philips Healthcare outside the submitted work which was paid into departmental funds and Charité Clinician Scientist Program. Drs. Spies (inventor), Willemeit (assignee), and Luetz (inventor) report issued patents related to the submitted work: European Patent 3 174 589 from July 31, 2015, European Patent 3 174 588 from July 31, 2015 and US Patent US 2017/0224950 A1 from August 10, 2017. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Objectives: To investigate the effect of extracorporeal cytokine reduction by CytoSorb (CytoSorbents, Monmouth Junction, NJ) on COVID-19-associated vasoplegic shock., Design: Prospective, randomized controlled pilot study., Setting: Eight ICUs at three sites of the tertiary-care university hospital Charité-Universitätsmedizin Berlin., Patients: COVID-19 patients with vasoplegic shock requiring norepinephrine greater than 0.2 µg/kg/min, C-reactive protein greater than 100 mg/L, and indication for hemodialysis., Interventions: Randomization of 1:1 to receive CytoSorb for 3-7 days or standard therapy. To account for inadvertent removal of antibiotics, patients in the treatment group received an additional dose at each adsorber change., Measurements and Main Results: The primary endpoint was time until resolution of vasoplegic shock, estimated by Cox-regression. Secondary endpoints included mortality, interleukin-6 concentrations, and catecholamine requirements. The study was registered in the German Registry of Clinical Trials (DRKS00021447). From November 2020 to March 2021, 50 patients were enrolled. Twenty-three patients were randomized to receive CytoSorb and 26 patients to receive standard of care. One patient randomized to cytokine adsorption was excluded due to withdrawal of informed consent. Resolution of vasoplegic shock was observed in 13 of 23 patients (56.5%) in the CytoSorb and 12 of 26 patients (46.2%) in the control group after a median of 5 days (interquartile range [IQR], 4-5 d) and 4 days (IQR, 3-5 d). The hazard ratio (HR) for the primary endpoint, adjusted for the predefined variables age, gender, extracorporeal membrane oxygenation-therapy, or time from shock onset to study inclusion was HR, 1.23 (95% CI, 0.54-2.79); p = 0.63. The mortality rate was 78% in the CytoSorb and 73% in the control group (unadjusted HR, 1.17 [95% CI, 0.61-2.23]; p = 0.64). The effects on inflammatory markers, catecholamine requirements, and the type and rates of adverse events were similar between the groups., Conclusions: In severely ill COVID-19 patients, CytoSorb did not improve resolution of vasoplegic shock or predefined secondary endpoints., Competing Interests: Dr. Enghard received honoraria from GlaxoSmithKline and AstraZeneca and filed two patents for novel urinary biomarkers outside the submitted work. Prof. Dr. Treskatsch received research funding and honoraria for workshops and lectures from Orionpharma, Edwards, Amomed, Cytosorbents, and Smith&Nephews all outside the submitted work. Prof. Dr. Spies received grants from Drägerwerk AG. KGaA; German Research Society; German Aerospace Center; Einstein Foundation Berlin; Federal Joint Committee (Gemeinsamer Bundesaussschuss [G-BA]); Inner University grants; Project Management Agency; Non-Profit Promoting Science and Education; European Society of Anesthesiology and Intensive Care; Baxter Deutschland GmbH; Cytosorbents Europe GmbH; Edwards Lifesciences Germany GmbH; Fresenius Medical Care; Grünenthal GmbH; Massimo Europe; Pfizer Pharma GmbH; Georg Thieme Verlag, Dr. F Köhler Chemie GmbH; Sintetica GmbH; Stifterverband für die deutsche Wissenschaft e.V./Philips; Stiftung Charié; Aguettant Deutschland GmbH; AbbVie Deutschland GmbH & KG; Amomed Pharma GmbH; InTouch Health; Copra System GmbH; Correvio GmbH; Max Plank Gesellschaft zur Förderung der Wissenschaften e.V.; Deutsche Gesellschaft für Anästhesiologie & Intensivmedizin; Stifterverband für die Deutsche Wissenschaft e.V./Medtronic; Philipps ElectronicsNederland BV; and the Federal Ministry of Health, (Bundesministerium für Gesundheit [BMG]), the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung [BMBF]), German Research Society all outside the submitted work. In addition, Prof. Dr. Spies has different patents. Dr. Khadzhynov received fees for speaking at a symposium organized on behalf of Fresenius Medical Care AG, Germany. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: Clinical trials evaluating the safety and effectiveness of sedative medication use in critically ill adults undergoing mechanical ventilation differ considerably in their methodological approach. This heterogeneity impedes the ability to compare results across studies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations convened a meeting of multidisciplinary experts to develop recommendations for key methodologic elements of sedation trials in the ICU to help guide academic and industry clinical investigators., Design: A 2-day in-person meeting was held in Washington, DC, on March 28-29, 2019, followed by a three-round, online modified Delphi consensus process., Participants: Thirty-six participants from academia, industry, and the Food and Drug Administration with expertise in relevant content areas, including two former ICU patients attended the in-person meeting, and the majority completed an online follow-up survey and participated in the modified Delphi process., Measurements and Main Results: The final recommendations were iteratively refined based on the survey results, participants' reactions to those results, summaries written by panel moderators, and a review of the meeting transcripts made from audio recordings. Fifteen recommendations were developed for study design and conduct, subject enrollment, outcomes, and measurement instruments. Consensus recommendations included obtaining input from ICU survivors and/or their families, ensuring adequate training for personnel using validated instruments for assessments of sedation, pain, and delirium in the ICU environment, and the need for methodological standardization., Conclusions: These recommendations are intended to assist researchers in the design, conduct, selection of endpoints, and reporting of clinical trials involving sedative medications and/or sedation protocols for adult ICU patients who require mechanical ventilation. These recommendations should be viewed as a starting point to improve clinical trials and help reduce methodological heterogeneity in future clinical trials., Competing Interests: The views expressed in this article are those of the authors, none of whom have financial conflicts of interest specifically related to the issues discussed in this article. At the time of the meeting (March 28–29, 2019) on which this article is based, several participants were employed by a pharmaceutical company or had received consulting fees or honoraria from one or more pharmaceutical or device companies. Meeting participants of this article who were not employed by industry at the time of the meeting received (or their Universities received) travel stipends, hotel accommodations, and meals during the meeting from the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the Food and Drug Administration. Drs. Ward, Aitken, Colantuoni, Maze, and Needham received funding from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, and Networks (ACTTION). Dr. Ward received support for article research from the University of Rochester Maine Medical Center Spectrum Medical Partners. Dr. Absalom’s institution received funding from The Medicines Company, Carefusion (BD), and Rigel; he received support for article research from Philips, Janssen Pharma, Johnson & Johnson, Ever Pharma, Orion, and Paion. Drs. Aitken, Brown, and Coursin received funding from Innovations Consulting Group LLC. Dr. Aitken also received funding from Elsevier Australia. Dr. Balas’ institution received funding from the National Institutes of Health (NIH), the National Heart, Lung, and Blood Institute, AACN research grant; she received funding from H3C and received support for article research from the NIH. Dr. Colantuoni received support for article research from ACTTION. Dr. Dexter received funding from the Division of Management Consulting of the University of Iowa’s Department of Anesthesia. Dr. Dworkin’s institution received funding from the U.S. Food and Drug Administration (FDA); he received funding from Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, AstraZeneca, Biogen, Biohaven, Boston Scientific, Braeburn, Celgene, Centrexion, Chromocell, Clexio, Collegium, Concert, Coronado, Daiichi Sankyo, Decibel, Dong-A, Editas, Eli Lilly, Eupraxia, Glenmark, Grace, Hope, Hydra, Immune, Johnson & Johnson, Lotus Clinical Research, Mainstay, Medavante, Merck, Neumentum, Neurana, NeuroBo, Novaremed, Novartis, NSGene, Olatec, Periphagen, Pfizer, Phosphagenics, Quark, Reckitt Benckiser, Regenacy, Relmada, Sanifit, Scilex, Semnur, SK Life Sciences, Sollis, Spinifex, Syntrix, Teva, Thar, Theranexus, Trevena, Vertex, and Vizuri. Dr. Girard received funding from Haisco Pharmaceutical. Dr. Hopkins’ institution received funding from Intermountain Medical and Research Foundation. Dr. Maze received funding from the University of California Office of the President and Cambridge University Press; he received support for article research from the NIH. Dr. Needham received funding from the FDA, Haisco-USA Pharmaceuticals, GlaxoSmithKline, and Novartis Pharma; he disclosed he is a principal investigator on a NIH-funded, multicentered randomized trial (R01HL132887) funded by Baxter Healthcare Corporation and Reck Medical Devices. Dr. Pandharipande’s institution received funding from Pfizer. Dr. Shehabi’s institution received funding from Orion Pharma and Pfizer; he received funding from Pfizer, Orion Pharma, Abbott Laboratories, and Ever Pharma. Dr. Sun received funding from UpToDate; she disclosed she is the Editor in Chief for UpToDate/Anesthesiology. Dr. Tung received funding from Anesthesia and Analgesia. Dr. Urman’s institution received funding from Medtronic/Covidien and AcelRx; he received funding from Merck, Sandoz, Heron, Takeda, and Pfizer. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Objectives: Intracranial hemorrhage is a serious complication in patients receiving venovenous extracorporeal membrane oxygenation during treatment of the acute respiratory distress syndrome. We analyzed timing, outcome, and risk factors of intracranial hemorrhage in patients on venovenous extracorporeal membrane oxygenation., Design: Retrospective cohort study., Setting: Single acute respiratory distress syndrome referral center., Patients: Patients receiving venovenous extracorporeal membrane oxygenation were identified from a cohort of 1,044 patients with acute respiratory distress syndrome. Patients developing an intracranial hemorrhage during venovenous extracorporeal membrane oxygenation therapy were compared with patients without evidence for intracranial hemorrhage. The primary objective was to assess the association of intracranial hemorrhage with 60-day mortality. Further objectives included the identification of risk factors for intracranial hemorrhage and the evaluation of clinical cutoff values., Interventions: None., Measurements and Main Results: Among 444 patients treated with venovenous extracorporeal membrane oxygenation, 49 patients (11.0% [95% CI, 8.3-14.4%]) developed an intracranial hemorrhage. The median time to intracranial hemorrhage occurrence was 4 days (95% CI, 2-7 d). Patients who developed an intracranial hemorrhage had a higher 60-day mortality compared with patients without intracranial hemorrhage (69.4% [54.4-81.3%] vs 44.6% [39.6-49.6%]; odds ratio 3.05 [95% CI, 1.54-6.32%]; p = 0.001). A low platelet count, a high positive end expiratory pressure, and a major initial decrease of Paco2 were identified as independent risk factors for the occurrence of intracranial hemorrhage. A platelet count greater than 100/nL and a positive end expiratory pressure less than or equal to 14 cm H2O during the first 7 days of venovenous extracorporeal membrane oxygenation therapy as well as a decrease of Paco2 less than 24 mm Hg during venovenous extracorporeal membrane oxygenation initiation were identified as clinical cutoff values to prevent intracranial hemorrhage (sensitivity 91% [95% CI, 82-99%], 94% [85-99%], and 67% [48-81%], respectively)., Conclusions: Intracranial hemorrhage occurs early during venovenous extracorporeal membrane oxygenation and is a determinant for 60-day mortality. Appropriate adjustment of identified modifiable risk factors might lower the prevalence of intracranial hemorrhage during venovenous extracorporeal membrane oxygenation therapy., Competing Interests: Dr. Graw received funding from CSL Behring, and he is a participant in the BIH-Charité Clinician Scientist Program funded by the Charité – Universitätsmedizin Berlin and the Berlin Institute of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: Hemophagocytic lymphohistiocytosis is a cytokine release syndrome caused by uncontrolled immune activation resulting in multiple organ failure and death. In this systematic review, we aimed to analyze triggers, various treatment modalities, and mortality in critically ill adult hemophagocytic lymphohistiocytosis patients., Data Sources: MEDLINE database (PubMed) at October 20, 2019., Study Selection: Studies and case series of patients greater than or equal to 18 years old, of whom at least one had to be diagnosed with hemophagocytic lymphohistiocytosis and admitted to an ICU., Data Extraction: Source data of studies and case series were summarized and analyzed on an individual basis. Multivariable logistic regression analysis was performed adjusting for age, sex, and trigger groups. Each single treatment agent was entered as a dichotomous variable to determine treatments associated with survival, regardless if given alone or in combination., Data Synthesis: In total, 661 patients from 65 studies and case series were included. Overall mortality was 57.8%. Infections were the most frequent trigger (49.9%), followed by malignancies (28.0%), autoimmune diseases (12.1%), unknown triggers (9.4%), and drugs (0.6%). Treatment with IV immunoglobulins was associated with improved survival (odds ratio, 0.548; 95% CI, 0.337-0.891; p = 0.015), while treatment with cyclosporine was associated with increased risk of death (odds ratio, 7.571; 95% CI, 3.702-15.483; p < 0.001). Considering different trigger groups separately, same results occurred only for infection-triggered hemophagocytic lymphohistiocytosis. No information was available on disease severity and other confounding factors., Conclusions: Mortality of hemophagocytic lymphohistiocytosis in the ICU is high. Most common triggers were infections. Results of survival analyses may be biased by treatment indication and disease severity. Future studies prospectively investigating treatment tailored to critically ill hemophagocytic lymphohistiocytosis patients are highly warranted.

Objective: Hyperferritinemia is frequently seen in critically ill patients. A rather rare though life-threatening condition related to severely elevated ferritin is hemophagocytic lymphohistiocytosis. We analyze ferritin levels to differentiate hemophagocytic lymphohistiocytosis from other causes of hyperferritinemia in a mixed cohort of critically ill patients., Design: Retrospective observational study., Setting: Adult surgical, anesthesiologic, and medical ICUs of a university hospital., Patients: Critical care patients (≥ 18 yr old) admitted to any of the adult ICUs at Charité - Universitätsmedizin Berlin between January 2006 and August 2018 with at least one ferritin value and hyperferritinemia (≥ 500 µg/L)., Interventions: None., Measurements and Main Results: Patients were categorized into hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other diagnoses. These were further categorized into 17 subgroups. Hemophagocytic lymphohistiocytosis diagnosis was based on Hemophagocytic Lymphohistiocytosis-2004 criteria and the HScore. Of 2,623 patients with hyperferritinemia, 40 were considered to have hemophagocytic lymphohistiocytosis (1.52%). Maximum ferritin levels were highest in hemophagocytic lymphohistiocytosis patients compared with all other disease groups (each p < 0.001). Sepsis and septic shock patients had higher maximum ferritin levels than patients with other diagnoses (each p < 0.001). A maximum ferritin value of 9,083 µg/L was at 92.5% sensitivity and 91.9% specificity for hemophagocytic lymphohistiocytosis (area under the curve, 0.963; 95% CI, 0.949-0.978). Of all subgroups with other diagnoses, maximum ferritin levels were highest in patients with varicella-zoster virus, hepatitis, or malaria (median, 1,935, 1,928, and 1,587 µg/L, respectively). Maximum ferritin levels were associated with increased in-hospital mortality (odds ratio, 1.518 per log µg/L [95% CI, 1.384-1.665 per log µg/L]; p < 0.001)., Conclusions: This is the largest study of patients with ferritin available in a mixed ICU cohort. Ferritin levels in patients with hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other conditions were distinctly different, with the highest ferritin levels observed in hemophagocytic lymphohistiocytosis patients. Maximum ferritin of 9,083 µg/L showed high sensitivity and specificity and, therefore, may contribute to improved diagnosis of hemophagocytic lymphohistiocytosis in ICU. The inclusion of ferritin into the sepsis laboratory panel is warranted.

Objectives: To evaluate test validity of the Pediatric Confusion Assessment Method for the ICU, the Pediatric Anesthesia Emergence Delirium scale, and the newly developed severity scale for the Pediatric Confusion Assessment Method for the ICU; to prospectively assess covariates and their influence on test validity of the scores., Design: Prospective observational cohort study., Setting: PICU of a tertiary care medical center., Patients: Critically ill patients 5 years old or older ventilated or nonventilated with an ICU length of stay of at least 24 hours., Interventions: None., Measurements and Main Results: Patients were scored with the Pediatric Confusion Assessment Method for the ICU and the Pediatric Anesthesia Emergence Delirium scale once daily for a maximum of 21 days. Validity was determined by comparing scoring results with the evaluations of the delirium experts who used the criteria of the Diagnostic and Statistical Manual, 4th Edition, Text Revision, for delirium diagnosis. Sixty-four patients were enrolled and 214 assessments were conducted and included in data analysis. The first assessments within each patient revealed sensitivities of 69.2% for the Pediatric Anesthesia Emergence Delirium scale, 76.9% for the Pediatric Confusion Assessment Method for the ICU, and 84.9% for the severity scale for the Pediatric Confusion Assessment Method for the ICU. Specificities were 98% for all scores. Considering repeated measurements, sensitivities decreased to 35.9% for the Pediatric Anesthesia Emergence Delirium scale and to 52.3% for the Pediatric Confusion Assessment Method for the ICU. The sensitivity of the severity scale for the Pediatric Confusion Assessment Method for the ICU dropped to 71.8%, which was significantly higher compared to the Pediatric Anesthesia Emergence Delirium scale (p = 0.0008). Receiver operator characteristic regression unveiled that sedation and mechanical ventilation had a significant negative effect on the validity of the Pediatric Anesthesia Emergence Delirium scale and the severity scale for the Pediatric Confusion Assessment Method for the ICU. Age and gender had a significant impact on the receiver operator characteristic curve of the severity scale for the Pediatric Confusion Assessment Method for the ICU., Conclusions: The severity scale for the Pediatric Confusion Assessment Method for the ICU showed the best test validity when used in critically ill children of 5 years old or older. Nevertheless, validity of delirium screening itself depends on patient specific factors. These factors should be taken into consideration when choosing a delirium screening instrument.

Background: Pneumonia accounts for almost half of intensive care unit (ICU) infections and nearly 60% of deaths from nosocomial infections. It increases hospital stay by 7-9 days, crude mortality by 70% and attributable mortality by 30%., Objective: Our purpose was to assess the impact of standard operating procedures adapted to the local resistance rates in the initial empirical treatment for pneumonia on duration of first pneumonia episode, duration of mechanical ventilation, and length of ICU stay., Design: Prospective observational cohort study with retrospective expert audit., Setting: Five anesthesiologically managed ICUs at University hospital (one cardio-surgical, one neurosurgical, two interdisciplinary, and one intermediate care)., Patients: Of 524 consecutive patients with > or = 36 hr ICU treatment 131 patients with pneumonia on ICU were identified. Their first pneumonia episode was evaluated daily for adherence to standard operating procedures. Pneumonia was diagnosed according to the American Thoracic Society guidelines. Patients with > 70% compliance were assigned to high adherence group (HAG), patients with < or = 70% to low adherence group (LAG)., Measurements and Results: HAG consisted of 45 (49 first episode) patients, LAG of 86 (82 first episode) patients, respectively. Mean duration of treatment of the first pneumonia episode was 10.11 +/- 7.95 days in the LAG and 6.22 +/- 3.27 days in the HAG (p = 0.001). Duration of mechanical ventilation was 317.59 +/- 336.18 hrs in the LAG and 178.07 +/- 191.33 hrs in the HAG (p = 0.017). Length of ICU stay was 20.24 +/- 16.59 days in the LAG and 12.04 +/- 10.42 days in the HAG (p = 0.001)., Limitations: Barriers in compliance need further evaluation., Conclusion: Adherence to standard operating procedure is associated with a shorter duration of treatment of first pneumonia episode, a shorter duration of mechanical ventilation, and a shorter ICU stay.

Objective: To assess the effects of epinephrine on splanchnic perfusion and splanchnic oxygen uptake in patients with septic shock., Design: Prospective, controlled trial., Setting: University hospital intensive care unit (ICU)., Patients: Eight patients with septic shock, according to the criteria of the 1992 American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference, requiring treatment with vasopressors., Interventions: We compared in crossover design a 2-hr infusion of epinephrine with dobutamine plus norepinephrine in eight ICU patients with septic shock. Systemic and splanchnic hemodynamics and oxygen transport were measured before and during treatment with epinephrine., Measurements and Main Results: There was essentially no effect of epinephrine on the global parameters, except for increased lactate concentrations. There were marked effects on the regional variables; epinephrine caused lower splanchnic flow and oxygen uptake, lower mucosal pH, and higher hepatic vein lactate., Conclusion: We conclude that undesirable splanchnic effects on patients in whom that region is particularly fragile should be considered when using epinephrine for septic shock treatment.

Objectives: To assess the effect of three different alcohol withdrawal therapy regimens in traumatized chronic alcoholic patients with respect to the duration of mechanical ventilation and the frequency of pneumonia and cardiac disorders during their intensive care unit (ICU) stay., Design: A prospective, randomized, blinded, controlled clinical trial., Setting: A university hospital ICU., Patients: Multiple-injured alcohol-dependent patients (n=180) transferred to the ICU after admission to the emergency room and operative management. A total of 180 patients were included in the study; however, 21 patients were excluded from the study after assignment., Interventions: Patients who developed actual alcohol withdrawal syndrome were randomized to one of the following treatment regimens: flunitrazepam/clonidine (n=54); chlormethiazole/haloperidol (n=50); or flunitrazepam/haloperidol (n=55). The need for administration of medication was determined, using a validated measure of the severity of alcohol withdrawal (Revised Clinical Institute Withdrawal Assessment for Alcohol Scale)., Measurements and Main Results: The duration of mechanical ventilation and major intercurrent complications, such as pneumonia, sepsis, cardiac disorders, bleeding disorders, and death, were documented. Patients did not differ significantly between groups regarding age, Revised Trauma and Injury Severity Score and Acute Physiology and Chronic Health Evaluation II score on admission. In all except four patients in the flunitrazepam/clonidine group, who continued to hallucinate, the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale decreased to <20 after initiation of therapy. ICU stay did not significantly differ between groups (p=.1669). However, mechanical ventilation was significantly prolonged in the chlormethiazole/haloperidol group (p=.0315) due to an increased frequency of pneumonia (p=.0414). Cardiac complications were significantly (p=.0047) increased in the flunitrazepam/clonidine group., Conclusions: There was some advantage in the flunitrazepam/clonidine regimen with respect to pneumonia and the necessity for mechanical ventilation. However, four (7%) patients had to be excluded from the study due to ongoing hallucinations during therapy. Also, cardiac complications were increased in this group. Thus, flunitrazepam/haloperidol should be preferred in patients with cardiac or pulmonary risk. Further studies are required to determine which therapy should be considered.

Objectives: Deactivation of endothelium-derived relaxing factor due to an increased oxygen radical load during sepsis may contribute to an impairment in microcirculatory blood flow. We investigated whether treatment with the sulfhydryl donor and oxygen radical scavenger, N-acetylcysteine, would improve whole-body oxygen consumption (VO2), gastric intramucosal pH, and veno-arterial CO2 gradient (veno-arterial PCO2) during septic shock., Design: Prospective, randomized, double-blind study conducted over 2 yrs., Setting: Septic shock patients admitted to the intensive care unit., Patients: Fifty-eight patients requiring hemodynamic monitoring (radial and pulmonary artery catheters) due to septic shock, were included in this study. All patients were examined within 72 hrs after the onset of sepsis. They were optimally resuscitated by conventional means with volume and inotropic agents, and exhibited stable clinical conditions (hemodynamic values, body temperature, hemoglobin, FIO2)., Interventions: A gastric tonometer was inserted to measure the gastric intramucosal pH. Subjects randomly received either 150 mg/kg of intravenous N-acetylcysteine or placebo over a 15-min period, then a continuous infusion of 12.5 mg/hr of N-acetylcysteine or placebo over approximately 90 mins., Measurements: Infusion measurements were begun 60 mins after the beginning of infusion and lasted approximately 30 mins. The infusion was then discontinued and 2 hrs later the final measurements were taken., Main Results: Basic patient characteristics (age, sex, Acute Physiology and Chronic Health Evaluation [APACHE] II scores, Multiple Organ Failure scores) did not differ significantly, nor did pre- and 2-hr postinfusion measurements differ between any of the groups. Thirteen (45%) patients responded (i.e., showed an increase in VO2 > 10%, reaching a mean of 19%) to the N-acetylcysteine infusion. The N-acetylcysteine responders also showed an increase in gastric intramucosal pH, a decrease in veno-arterial PCO2, an increase in oxygen delivery, cardiac index, stroke index, and left ventricular stroke work index, as well as a significant decrease in systemic vascular resistance in comparison to baseline. The N-acetylcysteine nonresponders, as well as the patients in the placebo group, did not show any significant changes in any of these variables. The N-acetylcysteine responders had a higher survival rate (69%) than the non-responders (19%) and were studied earlier after onset of sepsis (37 hrs) than the nonresponders (61 hrs). The only significant difference between the entire N-acetylcysteine group (which included responders plus nonresponders) and the placebo group was an increased VO2 in the entire N-acetylcysteine group during infusion measurements., Conclusions: N-acetylcysteine provided a transient improvement in tissue oxygenation in about half of the septic shock patients, as indicated by an increase in VO2 and gastric intramucosal pH and a decrease in veno-arterial PCO2. The higher survival rate in the N-acetylcysteine responders and the fact that half of the patients receiving N-acetylcysteine did not respond, suggests that, in some patients, sepsis irreversibly damages the microvasculature to the extent that N-acetylcysteine has no effect. If analyzed by intention to treat, the N-acetylcysteine did not produce effects that were significantly different from the placebo. Whether the N-acetylcysteine challenge was merely diagnostic or whether N-acetylcysteine can be effective in the treatment of sepsis deserves further investigation.