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Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

Objective: Terminal extubation (TE) and terminal weaning (TW) during withdrawal of life-sustaining therapies (WLSTs) have been described and defined in adults. The recent Death One Hour After Terminal Extubation study aimed to validate a model developed to predict whether a child would die within 1 hour after discontinuation of mechanical ventilation for WLST. Although TW has not been described in children, pre-extubation weaning has been known to occur before WLST, though to what extent is unknown. In this preplanned secondary analysis, we aim to describe/define TE and pre-extubation weaning (PW) in children and compare characteristics of patients who had ventilatory support decreased before WLST with those who did not., Design: Secondary analysis of multicenter retrospective cohort study., Setting: Ten PICUs in the United States between 2009 and 2021., Patients: Nine hundred thirteen patients 0-21 years old who died after WLST., Interventions: None., Measurements and Main Results: 71.4% ( n = 652) had TE without decrease in ventilatory support in the 6 hours prior. TE without decrease in ventilatory support in the 6 hours prior = 71.4% ( n = 652) of our sample. Clinically relevant decrease in ventilatory support before WLST = 11% ( n = 100), and 17.6% ( n = 161) had likely incidental decrease in ventilatory support before WLST. Relevant ventilator parameters decreased were F io2 and/or ventilator set rates. There were no significant differences in any of the other evaluated patient characteristics between groups (weight, body mass index, unit type, primary diagnostic category, presence of coma, time to death after WLST, analgosedative requirements, postextubation respiratory support modality)., Conclusions: Decreasing ventilatory support before WLST with extubation in children does occur. This practice was not associated with significant differences in palliative analgosedation doses or time to death after extubation., Competing Interests: Dr. Pringle’s institution received funding from the National Institutes of Health (NIH) (Ul1TR001427); she received support for article research from the NIH. Dr. Winter received support for article research from the LK Whittier Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock., Design: Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities., Methods: Each task force member submitted five research questions on any sepsis-related subject. Committee members then independently ranked their top three priorities from the list generated. The highest rated clinical and basic science questions were developed into the current article., Results: A total of 81 questions were submitted. After merging similar questions, there were 34 clinical and ten basic science research questions submitted for voting. The five top clinical priorities were as follows: 1) what is the best strategy for screening and identification of patients with sepsis, and can predictive modeling assist in real-time recognition of sepsis? 2) what causes organ injury and dysfunction in sepsis, how should it be defined, and how can it be detected? 3) how should fluid resuscitation be individualized initially and beyond? 4) what is the best vasopressor approach for treating the different phases of septic shock? and 5) can a personalized/precision medicine approach identify optimal therapies to improve patient outcomes? The five top basic science priorities were as follows: 1) How can we improve animal models so that they more closely resemble sepsis in humans? 2) What outcome variables maximize correlations between human sepsis and animal models and are therefore most appropriate to use in both? 3) How does sepsis affect the brain, and how do sepsis-induced brain alterations contribute to organ dysfunction? How does sepsis affect interactions between neural, endocrine, and immune systems? 4) How does the microbiome affect sepsis pathobiology? 5) How do genetics and epigenetics influence the development of sepsis, the course of sepsis and the response to treatments for sepsis?, Conclusions: Knowledge advances in multiple clinical domains have been incorporated in progressive iterations of the Surviving Sepsis Campaign guidelines, allowing for evidence-based recommendations for short- and long-term management of sepsis. However, the strength of existing evidence is modest with significant knowledge gaps and mortality from sepsis remains high. The priorities identified represent a roadmap for research in sepsis and septic shock., Competing Interests: Drs. De Backer, Pontes Azevedo, and Tissieres received funding from Baxter. Dr. De Backer received funding from Edwards Lifesciences, Phillips, and Viatris Pharmazz. Dr. Deutschman received funding from Elsevier, Siemens Healthcare Diagnostics (Tarrytown, NY), Enliven (Jerusalem, Israel), The Society of Critical Care Medicine, the National Institute of General Medical Sciences, and La Jolla Pharmaceuticals; he received support for article research form the National Institutes of Health (NIH); he received Giapreza (angiotensin II infusion) for experimental use from La Jolla Pharmaceuticals (La Jolla, CA); and he received honorarium for serving as Scientific Editor of the journal Critical Care Medicine. Dr. Ostermann received research funding from Baxter, Fresenius Medical, bioMerieux, and La Jolla Pharma. Dr. Talmor received funding from NIH, Clew Medical, Mindray, and STIMIT. Dr. Prescott’s institution received funding from the NIH, U.S. Department of Veterans Affairs, the Agency for Healthcare and Research and Quality, the U.S. Centers for Disease Control and Prevention, and Blue Cross Blue Shield Michigan; she disclosed government work. Dr. Antonelli received funding from General Electrics, Fisher & Paykel, Menarini, and Pfizer. Dr. Pontes Azevedo received funding from Merck Sharp Dohme (MSD) and Nestle. Dr. Loeches received funding from ThermoFisher, Polyphor, MSD, Fresenius Kabi, Gilead, Clinigen, Biotest, Accelerate, and bioMérieux. Dr. Tissieres received funding from Sanofi, bioMerieux, Abionic, Sedana, and ThermoFisher. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: To identify research priorities in the management, pathophysiology, and host response of coronavirus disease 2019 in critically ill patients., Design: The Surviving Sepsis Research Committee, a multiprofessional group of 17 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine, was virtually convened during the coronavirus disease 2019 pandemic. The committee iteratively developed the recommendations and subsequent document., Methods: Each committee member submitted a list of what they believed were the most important priorities for coronavirus disease 2019 research. The entire committee voted on 58 submitted questions to determine top priorities for coronavirus disease 2019 research., Results: The Surviving Sepsis Research Committee provides 13 priorities for coronavirus disease 2019. Of these, the top six priorities were identified and include the following questions: 1) Should the approach to ventilator management differ from the standard approach in patients with acute hypoxic respiratory failure?, 2) Can the host response be modulated for therapeutic benefit?, 3) What specific cells are directly targeted by severe acute respiratory syndrome coronavirus 2, and how do these cells respond?, 4) Can early data be used to predict outcomes of coronavirus disease 2019 and, by extension, to guide therapies?, 5) What is the role of prone positioning and noninvasive ventilation in nonventilated patients with coronavirus disease?, and 6) Which interventions are best to use for viral load modulation and when should they be given?, Conclusions: Although knowledge of both biology and treatment has increased exponentially in the first year of the coronavirus disease 2019 pandemic, significant knowledge gaps remain. The research priorities identified represent a roadmap for investigation in coronavirus disease 2019., Competing Interests: Dr. Deutschman is past president of the Society of Critical Care Medicine, is a scientific editor for Critical Care Medicine, and is a consultant for Enlivex and Lowell Therapeutics; his institution received funding from National Institute of General Medical Sciences; he received funding from the Society of Critical Care Medicine, Elsevier, Enlivex, Sage Therapeutics, and La Jolla Pharmaceuticals; and he received support for article research from the National Institutes of Health (NIH). Dr. Evans disclosed that she serves as the cochair of the Surviving Sepsis Committee and as the adult Surviving Sepsis Campaign Guidelines for the management of sepsis and septic shock. Dr. Ferrer received funding from MSD, Pfizer, and Gilead. Dr. Kesecioglu is president of the European Society of Intensive Care Medicine. Dr. Kissoon is the pediatrics guidelines cochair of the Surviving Sepsis Committee. Dr. Martin-Loeches received honoraria from MSD, Gilead, and Aspen. Dr. Nunnally is Treasurer of the Society of Critical Care Anesthesiologists. Dr. Prescott is the sepsis lead for a Michigan statewide sepsis quality improvement initiative sponsored by Blue Cross Blue Shield of Michigan, and his institution received funding from Agency for Healthcare Research and Quality, the Department of Veterans Affairs, and the NIH, and she disclosed government work. Dr. Rhodes is the adult guidelines cochair of the Surviving Sepsis Committee and a member of the Executive Committee. Dr. Talmor received speaking fees from Hamilton Medical, Clew, and Mindray. Dr. Tissieres is president of the European Society of Pediatric and Neonatal Intensive Care, is the pediatrics guidelines cochair of the Surviving Sepsis Committee, and has received consulting fees or research grant from Baxter, bioMerieux, Sanofi. Dr. DeBacker is past president of the European Society of Intensive Care Medicine and has received consulting fees from Fresenius Kabi. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: Noninvasive ventilation is widely used to avoid tracheal intubation in critically ill children. The objective of this study was to assess whether noninvasive ventilation failure was associated with severe tracheal intubation-associated events and severe oxygen desaturation during tracheal intubation., Design: Prospective multicenter cohort study of consecutive intubated patients using the National Emergency Airway Registry for Children registry., Setting: Thirteen PICUs (in 12 institutions) in the United States and Canada., Patients: All patients undergoing tracheal intubation in participating sites were included. Noninvasive ventilation failure group included children with any use of high-flow nasal cannula, continuous positive airway pressure, or bilevel noninvasive ventilation in the 6 hours prior to tracheal intubation. Primary tracheal intubation group included children without exposure to noninvasive ventilation within 6 hours before tracheal intubation., Interventions: None., Measurements and Main Results: Severe tracheal intubation-associated events (cardiac arrest, esophageal intubation with delayed recognition, emesis with aspiration, hypotension requiring intervention, laryngospasm, pneumothorax, pneumomediastinum) and severe oxygen desaturation (< 70%) were recorded prospectively. The study included 956 tracheal intubation encounters; 424 tracheal intubations (44%) occurred after noninvasive ventilation failure, with a median of 13 hours (interquartile range, 4-38 hr) of noninvasive ventilation. Noninvasive ventilation failure group included more infants (47% vs 33%; p < 0.001) and patients with a respiratory diagnosis (56% vs 30%; p < 0.001). Noninvasive ventilation failure was not associated with severe tracheal intubation-associated events (5% vs 5% without noninvasive ventilation; p = 0.96) but was associated with severe desaturation (15% vs 9% without noninvasive ventilation; p = 0.005). After controlling for baseline differences, noninvasive ventilation failure was not independently associated with severe tracheal intubation-associated events (p = 0.35) or severe desaturation (p = 0.08). In the noninvasive ventilation failure group, higher FIO2 before tracheal intubation (≥ 70%) was associated with severe tracheal intubation-associated events., Conclusions: Critically ill children are frequently exposed to noninvasive ventilation before intubation. Noninvasive ventilation failure was not independently associated with severe tracheal intubation-associated events or severe oxygen desaturation compared to primary tracheal intubation.

Objectives: Tracheal intubation in critically ill children with shock poses a risk of hemodynamic compromise. Ketamine has been considered the drug of choice for induction in these patients, but limited data exist. We investigated whether the administration of ketamine for tracheal intubation in critically ill children with or without shock was associated with fewer adverse hemodynamic events compared with other induction agents. We also investigated if there was a dose dependence for any association between ketamine use and adverse hemodynamic events., Design: We performed a retrospective analysis using prospectively collected observational data from the National Emergency Airway Registry for Children database from 2013 to 2017., Setting: Forty international PICUs participating in the National Emergency Airway Registry for Children., Patients: Critically ill children 0-17 years old who underwent tracheal intubation in a PICU., Interventions: None., Measurements and Main Results: The association between ketamine exposure as an induction agent and the occurrence of adverse hemodynamic events during tracheal intubation including dysrhythmia, hypotension, and cardiac arrest was evaluated. We used multivariable logistic regression to account for patient, provider, and practice factors with robust SEs to account for clustering by sites. Of 10,750 tracheal intubations, 32.0% (n = 3,436) included ketamine as an induction agent. The most common diagnoses associated with ketamine use were sepsis and/or shock (49.7%). After adjusting for potential confounders and sites, ketamine use was associated with fewer hemodynamic tracheal intubation associated adverse events compared with other agents (adjusted odds ratio, 0.74; 95% CI, 0.58-0.95). The interaction term between ketamine use and indication for shock was not significant (p = 0.11), indicating ketamine effect to prevent hemodynamic adverse events is consistent in children with or without shock., Conclusions: Ketamine use for tracheal intubation is associated with fewer hemodynamic tracheal intubation-associated adverse events.

Objectives: Interventional trials on glucocorticoids in sepsis have yielded capricious results. Recent studies have identified multiple glucocorticoid receptor isoforms. The relative abundance of these isoforms in septic patients and following murine cecal ligation and puncture is unknown. The objective of this study is to determine the effects of cecal ligation and puncture on glucocorticoid receptor isoform abundance., Design: Determination of effects of cecal ligation and puncture on glucocorticoid receptor isoform subtype abundance in C57BL/6 mice. Examination of glucocorticoid receptor isoform abundance in tissues harvested from patients immediately after death from sepsis or nonseptic critical illness., Setting: Research laboratory., Subjects: C57BL/6 mice and human tissue sections from recently deceased critically ill patients., Interventions: C57BL/6 mice were subjected to cecal ligation and puncture or sham operation. Abundance of the activating glucocorticoid receptor α and the inactivating glucocorticoid receptor β isoforms was determined in mouse and human tissue using immunoblotting. Cardiac output with or without stimulation with dexamethasone was assessed using echocardiography. The expression of the gene encoding the glucocorticoid-dependent enzyme glucose-6-phosphatase was identified using polymerase chain reaction. Statistical significance (p < 0.05) was determined using analysis of variance., Measurements and Main Results: Results in baseline and sham operation mice were identical. At baseline, glucocorticoid receptor αA predominated in heart, lung, and skeletal muscle; abundance was decreased post cecal ligation and puncture. All glucocorticoid receptor α subtypes were identified in liver. Cecal ligation and puncture decreased the summed abundance of hepatic glucocorticoid receptor α subtypes and those of glucocorticoid receptors αA, B, and D. However, glucocorticoid receptor αC abundance was unchanged. Cecal ligation and puncture increased glucocorticoid receptor β protein abundance in the heart and lung. Relative to T0, cecal ligation and puncture decreased cardiac output and attenuated the cardiac output response to dexamethasone. Cecal ligation and puncture also decreased expression of glucose-6-phosphatase. Compared with nonseptic patients, human sepsis decreased the abundance of glucocorticoid receptor α and increased the abundance of glucocorticoid receptor β in heart and liver biopsies., Conclusions: Cecal ligation and puncture altered glucocorticoid receptor α and glucocorticoid receptor β isoform expression in tissues and decreased functional responses in heart and liver. Decreases in glucocorticoid receptor α and increases in glucocorticoid receptor β might explain the diminished glucocorticoid responsiveness observed in sepsis.

Objective: To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock., Design: A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations., Methods: Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (Supplemental Table 1, Supplemental Digital Content 2, http://links.lww.com/CCM/D636) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science., Results: The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: 1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; 2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; 3) should rapid diagnostic tests be implemented in clinical practice?; 4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; 5) what are the predictors of sepsis long-term morbidity and mortality?; and 6) what information identifies organ dysfunction?, Conclusions: While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

Objectives: The prevalence of responsiveness to initial fluid challenge among hypotensive sepsis patients is unclear. To avoid fluid overload, and unnecessary treatment, it is important to differentiate these phenotypes. We aimed to 1) determine the proportion of hypotensive sepsis patients sustaining favorable hemodynamic response after initial fluid challenge, 2) determine demographic and clinical risk factors that predicted refractory hypotension, and 3) assess the association between timeliness of fluid resuscitation and refractoriness., Design: Secondary analysis of a prospective, multisite, observational, consecutive-sample cohort., Setting: Nine tertiary and community hospitals over 1.5 years., Patients: Inclusion criteria 1) suspected or confirmed infection, 2) greater than or equal to two systemic inflammatory response syndrome criteria, 3) systolic blood pressure less than 90 mm Hg, greater than 40% decrease from baseline, or mean arterial pressure less than 65 mm Hg., Measurements and Main Results: Sex, age, heart failure, renal failure, immunocompromise, source of infection, initial lactate, coagulopathy, temperature, altered mentation, altered gas exchange, and acute kidney injury were used to generate a risk score. The primary outcome was sustained normotension after fluid challenge without vasopressor titration. Among 3,686 patients, 2,350 (64%) were fluid responsive. Six candidate risk factors significantly predicted refractoriness in multivariable analysis: heart failure (odds ratio, 1.43; CI, 1.20-1.72), hypothermia (odds ratio, 1.37; 1.10-1.69), altered gas exchange (odds ratio, 1.33; 1.12-1.57), initial lactate greater than or equal to 4.0 mmol/L (odds ratio, 1.28; 1.08-1.52), immunocompromise (odds ratio, 1.23; 1.03-1.47), and coagulopathy (odds ratio, 1.23; 1.03-1.48). High-risk patients (≥ three risk factors) had 70% higher (CI, 48-96%) refractory risk (19% higher absolute risk; CI, 14-25%) versus low-risk (zero risk factors) patients. Initiating fluids in greater than 2 hours also predicted refractoriness (odds ratio, 1.96; CI, 1.49-2.58). Mortality was 15% higher (CI, 10-18%) for refractory patients., Conclusions: Two in three hypotensive sepsis patients were responsive to initial fluid resuscitation. Heart failure, hypothermia, immunocompromise, hyperlactemia, and coagulopathy were associated with the refractory phenotype. Fluid resuscitation initiated after the initial 2 hours more strongly predicted refractoriness than any patient factor tested.

Objectives: The objectives of this study were to 1) assess patterns of early crystalloid resuscitation provided to sepsis and septic shock patients at initial presentation and 2) determine the association between time to initial crystalloid resuscitation with hospital mortality, mechanical ventilation, ICU utilization, and length of stay., Design: Consecutive-sample observational cohort., Setting: Nine tertiary and community hospitals over 1.5 years., Patients: Adult sepsis and septic shock patients captured in a prospective quality improvement database inclusion criteria: suspected or confirmed infection, greater than or equal to two systemic inflammatory response criteria, greater than or equal to one organ-dysfunction criteria., Interventions: The primary exposure was crystalloid initiation within 30 minutes or lesser, 31-120 minutes, or more than 120 minutes from sepsis identification., Measurements and Main Results: We identified 11,182 patients. Crystalloid initiation was faster for emergency department patients (β, -141 min; CI, -159 to -125; p < 0.001), baseline hypotension (β, -39 min; CI, -48 to -32; p < 0.001), fever, urinary or skin/soft-tissue source of infection. Initiation was slower with heart failure (β, 20 min; CI, 14-25; p < 0.001), and renal failure (β, 16 min; CI, 10-22; p < 0.001). Five thousand three hundred thirty-six patients (48%) had crystalloid initiated in 30 minutes or lesser versus 2,388 (21%) in 31-120 minutes, and 3,458 (31%) in more than 120 minutes. The patients receiving fluids within 30 minutes had lowest mortality (949 [17.8%]) versus 31-120 minutes (446 [18.7%]) and more than 120 minutes (846 [24.5%]). Compared with more than 120 minutes, the adjusted odds ratio for mortality was 0.76 (CI, 0.64-0.90; p = 0.002) for 30 minutes or lesser and 0.76 (CI, 0.62-0.92; p = 0.004) for 31-120 minutes. When assessed continuously, mortality odds increased by 1.09 with each hour to initiation (CI, 1.03-1.16; p = 0.002). We observed similar patterns for mechanical ventilation, ICU utilization, and length of stay. We did not observe significant interaction for mortality risk between initiation time and baseline heart failure, renal failure, hypotension, acute kidney injury, altered gas exchange, or emergency department (vs inpatient) presentation., Conclusions: Crystalloid was initiated significantly later with comorbid heart failure and renal failure, with absence of fever or hypotension, and in inpatient-presenting sepsis. Earlier crystalloid initiation was associated with decreased mortality. Comorbidities and severity did not modify this effect.

Objectives: To determine mortality and costs associated with adherence to an aggressive, 3-hour sepsis bundle versus noncompliance with greater than or equal to one bundle element for severe sepsis and septic shock patients., Design: Prospective, multisite, observational study following three sequential, independent cohorts, from a single U.S. health system, through their hospitalization., Setting: Cohort 1: five tertiary and six community hospitals. Cohort 2: single tertiary, academic medical center. Cohort 3: five tertiary and four community hospitals., Patients: Consecutive sample of all severe sepsis and septic shock patients (defined: infection, ≥ 2 systemic inflammatory response syndrome, and hypoperfusive organ dysfunction) identified by a quality initiative. The exposure was full 3-hour bundle compliance. Bundle elements are as follows: 1) blood cultures before antibiotics; 2) parenteral antibiotics administered less than or equal to 180 minutes from greater than or equal to two systemic inflammatory response syndrome "and" lactate ordered, or less than or equal to 60 minutes from "time-zero," whichever occurs earlier; 3) lactate result available less than or equal to 90 minutes postorder; and 4) 30 mL/kg IV crystalloid bolus initiated less than or equal to 30 minutes from "time-zero." Main outcomes were in-hospital mortality (all cohorts) and total direct costs (cohorts 2 and 3)., Measurements and Main Results: Cohort 1: 5,819 total patients; 1,050 (18.0%) bundle compliant. Mortality: 604 (22.6%) versus 834 (26.5%); CI, 0.9-7.1%; adjusted odds ratio, 0.72; CI, 0.61-0.86; p value is less than 0.001. Cohort 2: 1,697 total patients; 739 (43.5%) bundle compliant. Mortality: 99 (13.4%) versus 171 (17.8%), CI, 1.0-7.9%; adjusted odds ratio, 0.60; CI, 0.44-0.80; p value is equal to 0.001. Mean costs: $14,845 versus $20,056; CI, -$4,798 to -5,624; adjusted β, -$2,851; CI, -$4,880 to -822; p value is equal to 0.006. Cohort 3: 7,239 total patients; 2,115 (29.2%) bundle compliant. Mortality: 383 (18.1%) versus 1,078 (21.0%); CI, 0.9-4.9%; adjusted odds ratio, 0.84; CI, 0.73-0.96; p value is equal to 0.013. Mean costs: $17,885 versus $22,108; CI, -$2,783 to -5,663; adjusted β, -$1,423; CI, -$2,574 to -272; p value is equal to 0.015., Conclusions: In three independent cohorts, 3-hour bundle compliance was associated with improved survival and cost savings.

Objective: Current guidelines recommend the use of intraosseous access when IV access is not readily attainable. The pediatric literature reports an excellent safety profile, whereas only small prospective studies exist in the adult literature. We report a case of vasopressor extravasation and threatened limb perfusion related to intraosseous access use and our management of the complication. We further report our subsequent systematic review of intraosseous access in the adult population., Data Sources: Ovid Medline was searched from 1946 to January 2015., Study Selection: Articles pertaining to intraosseous access in the adult population (age greater than or equal to 14 years) were selected. Search terms were "infusion, intraosseous" (all subfields included), and intraosseous access" as key words., Data Extraction: One author conducted the initial literature review. All authors assessed the methodological quality of the studies and consensus was used to ensure studies met inclusion criteria., Data Synthesis: The case of vasopressor extravasation was successfully treated with pharmacologic interventions, which reversed the effects of the extravasated vasopressors: intraosseous phentolamine, topical nitroglycerin ointment, and intraarterial verapamil and nitroglycerin. Our systematic review of the adult literature found 2,332 instances of intraosseous insertion. A total of 2,106 intraosseous insertion attempts were made into either the tibia or the humerus; 192 were unsuccessful, with an overall success rate of 91%. Five insertions were associated with serious complications. A total of 226 insertion attempts were made into the sternum; 54 were unsuccessful, with an overall success rate of 76%., Conclusions: Intraosseous catheter insertion provides a means for rapid delivery of medications to the vascular compartment with a favorable safety profile. Our systematic literature review of adult intraosseous access demonstrates an excellent safety profile with serious complications occurring in 0.3% of attempts. We report an event of vasopressor extravasation that was potentially limb threatening. Therapy included local treatment and injection of intraarterial vasodilators. Intraosseous access complications should continue to be reported, so that the medical community will be better equipped to treat them as they arise.

Objectives: a) To determine whether decreased sarcoplasmic calcium release channel (CRC) activity is a mechanism by which myocardial contractility is reduced in endotoxemia; b) to determine whether nitric oxide modulates CRC activity in endotoxemia; and c) to examine two nitric oxide signaling pathways in relation to CRC function in endotoxemia., Design: Randomized, prospective using a rat model of endotoxemia., Setting: : Research laboratory., Subjects: Sprague-Dawley rats., Interventions: Endotoxemia was induced by lipopolysaccharide administration. The effects of nitric oxide were studied using the highly selective inducible nitric oxide synthase inhibitor N-(3-(aminomethyl)benzyl)acetamidine dihydrochloride (1400W) and the specific guanylyl cyclase inhibitor 1-H (1, 2, 4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ)., Measurements and Main Results: We assessed myocardial contractility, myocardial nitric oxide content, and guanosine-3',5' (cyclic) phosphate (cGMP) content. We determined CRC activity by calcium release and ryanodine binding assays. We followed these variables at four time points through the course of endotoxemia. We found that myocardial contractility and CRC activity were decreased in late but not in early endotoxemia. Furthermore, inducible nitric oxide synthase inhibition with 1400W restored contractility and CRC activity in late endotoxemia but paradoxically worsened these variables in early endotoxemia. Through the use of the guanylyl cyclase inhibitor ODQ, we demonstrate that nitric oxide acts through cGMP-mediated mechanisms in early and late endotoxemia. We investigated cGMP-independent pathways by assessing the oxidative status of the CRC. We found that in late endotoxemia, nitric oxide decreased the number of free thiols, demonstrating that nitric oxide also acts through cGMP-independent pathways., Conclusions: Nitric oxide has a dual effect on the CRC in endotoxemia. At low concentrations, as measured in early endotoxemia, nitric oxide stabilizes the CRC through cGMP-mediated mechanisms. In late endotoxemia, high nitric oxide concentrations decrease channel activity through both cGMP-dependent and cGMP-independent mechanisms.

Objectives: To determine the time course for myocardial production of nitric oxide, peroxynitrite, and glutathione, to determine the activities of the myocardial antioxidant enzymes glutathione peroxidase, superoxide dismutase, and glutathione reductase throughout endotoxemia and into recovery, and to correlate the levels of these variables to left ventricular contractility in endotoxemia., Design: Rats were treated with lipopolysaccharide. Endotoxemic hearts were examined at baseline, 4, 16, 24, and 48 hrs after lipopolysaccharide. Saline time-control groups were treated identically., Setting: A pulmonary research laboratory of a university teaching hospital., Measurements and Main Results: Lipopolysaccharide administration resulted in decreased contractility at 16 hrs as assessed by the isolated papillary muscle technique. Contractility recovered by 24 hrs. Myocardial glutathione content initially increased, but it was decreased from baseline by 16 hrs, as was glutathione peroxidase activity. Both superoxide dismutase and glutathione reductase activities were increased early (4 hrs) and remained elevated throughout the course of the experiment. Myocardial nitric oxide content (assessed by the chemiluminescence technique) was increased by 4 hrs and was markedly elevated by 16 hrs. Nitric oxide levels remained elevated despite recovery of contractility at 24 hrs. Similarly, peroxynitrite (assessed by measurement of 3-nitrotyrosine by high-pressure liquid chromatography) was elevated at 16 hrs and remained elevated despite normalization of contractility at 24 and 48 hrs., Conclusions: Myocardial dysfunction in endotoxemia correlates mainly with decreased glutathione content and glutathione peroxidase activity rather than nitric oxide or peroxynitrite formation. These data indicate that lipopolysaccharide-induced myocardial dysfunction is not solely caused by elevated myocardial nitric oxide levels but rather caused by the sum of complex interactions between various oxygen- and nitrogen-derived radicals.

Objective: To report an unusual, life-threatening combination of neurologic, cardiac, and gastrointestinal symptoms in the presence of a community-acquired pneumonia., Design: Case report., Setting: University hospital., Patient: Previously healthy young male., Intervention: Diagnostic fiberoptic bronchoscopy, lumber puncture, magnetic resonance imaging of the brain, and institution of systemic antibiotics., Main Result: Gradual clinical improvement of a multiple-system illness., Conclusion: Legionellosis should be considered in the differential diagnosis of patients presenting with neurologic, cardiac, and gastrointestinal symptoms, particularly in the presence of radiographic pneumonia. Furthermore, Legionella meningoencephalitis may present with findings on magnetic resonance imaging previously thought to be characteristic of herpes encephalitis.

Objective: To compare the cardiopulmonary and peripheral circulatory effects of the nonselective nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) to the more selective inducible NOS inhibitor S-methylisothiourea (SMT) and to phenylephrine (PE) in endotoxic and normal swine., Design: Prospective, randomized, unblinded study., Setting: Research laboratory of academic medical center., Subjects: Nonanesthetized, sedated, mechanically ventilated, minimally invasive swine model., Interventions: Animals received either lipopolysaccharide (LPS, LPS groups) or equivalent volume of saline (normal groups). LPS animals were further randomized into four groups when mean arterial pressure (MAP) had dropped to <60 mm Hg: the LPS/saline group received saline only; the other groups received either L-NAME, SMT, or PE. These were titrated to elevate MAP by 20-25 mm Hg, and animals were followed for another 3 hrs. Pulmonary artery occlusion pressure was maintained at one to two times baseline with the infusion of saline. Normal groups received the same agents 1 hr after baseline measurements, and drugs were titrated to achieve similar increases in MAP. We measured gastric-arterial PCO2 gradient by tonometry as an index of gastric mucosal perfusion. Left ventricular volumes were determined echocardiographically; right ventricular volumes were determined by a pulmonary arterial catheter equipped with a rapid thermistor. Plasma nitrite/nitrate (NOx) concentrations were measured hourly., Measurements and Main Results: In the LPS groups, all agents elevated MAP and systemic vascular resistance similarly. By hr 4, cardiac output had decreased in all groups, but the decrease with L-NAME (35% +/- 16%) occurred earlier (at hr 3) and was larger than the decrease with SMT at hrs 3 and 5 and larger than the decrease with saline at hrs 3 to 5. L-NAME resulted in a larger increase in mean pulmonary arterial pressure (MPAP) when compared with saline (130% +/- 44% vs. 61% +/- 25%; p < .001) and SMT groups (130% vs. 97% +/- 80%; p < .007). Only L-NAME had detrimental effects on right ventricular function as indicated by an increase in right ventricular end-systolic volume (54 +/- 10 to 87 +/-6 mL; p < .05) and right ventricular end-diastolic volume (90 +/-11 to 128 +/- 18 mL; p < .05). SMT decreased both left ventricular end-systolic volume (10.4 +/- 2 to 7.7 +/- 4 mL; p < .05) and left ventricular end-diastolic volume (18.5 +/- 3 to 14.2 +/- 5 mL; p < .05), indicating improved left ventricular function, whereas L-NAME did not affect left ventricular volumes. Both SMT and PE corrected LPS-induced gastric mucosal acidosis, but L-NAME did not. We did not detect changes in plasma NOx concentrations in any of LPS groups. In the normal groups, all agents increased MAP without changes in plasma NOx concentrations. L-NAME caused a larger decrease in cardiac output, but the increase in MPAP was higher with SMT. Both NOS inhibitors led to left ventricular dilation, but PE did not. Only L-NAME caused right ventricular dilation. There were no changes in gastric-arterial PCO2 gradient., Conclusions: In LPS animals, we failed to detect changes in plasma NOx concentrations. Furthermore, for similar increases in MAP, SMT improved gastric mucosal acidosis, had less adverse effects on right ventricular function and MPAP, and may have improved left ventricular function. However, apart from its bene-ficial effects on left ventricular function, SMT was not superior to PE. The results from normal animals indicate that both NOS inhibitors have adverse effects on cardiac function beyond those attributed to increased MAP.

Objective: To describe a method of rapid fluid removal in children with anasarca and the acute respiratory distress syndrome (ARDS) secondary to sepsis or the systemic inflammatory response syndrome., Design: Consecutive case series., Setting: Pediatric Intensive Care Unit of a children's hospital., Patients: Six patients with ARDS secondary to sepsis or systemic inflammatory response syndrome, who had persistent anasarca complicating their respiratory course despite intravenous diuretic therapy., Interventions: Continuous flow peritoneal dialysis (CFPD) was instituted after percutaneously inserting two Tenckhoff dialysis catheters into the peritoneal cavity of each patient and tunneling them through the subcutaneous tissue to exit from opposite lower abdominal quadrants. A dialysis solution with 2.5% dextrose was administered continuously via one of the catheters at a rate ranging from 10-30 mL/kg/hr, and concomitantly drained via the other catheter. The concentration of the dialysis solution and rate of inflow were adjusted as needed to achieve the desired peritoneal outflow rate. CFPD was discontinued when adequate weight loss had occurred and the patient's daily urine output exceeded their daily fluid intake. The patient's overall fluid balance and change in weight were recorded daily. The PaO2/FiO2 ratio, alveolar-arterial oxygen gradient, and oxygenation index were also calculated daily., Measurements and Main Results: Six patients with ARDS, mean age 18.7+/-37.0 months were mechanically ventilated for 8.0+/-4.0 days before CFPD, during which time average body weight increased to 63%+/-22% above admission body weight, despite the use of intravenous diuretic therapy. They underwent CFPD for 126.7+/-60.0 hrs, during which time their body weight decreased to 30%+/-12% above admission weight (p<.05). During dialysis, the dialysis outflow rate exceeded the inflow rate by 4.2+/-0.9 mL/kg/hr. When compared with values calculated immediately before starting CFPD, post-CFPD PaO2/FiO2 increased from 97.0+/-32.0 to 215.0+/-40.4 mm Hg (12.9+/-4.3 to 28.7+/-5.4 kPa) (p<.05), post-CFPD alveolar-arterial oxygen gradient decreased from 390.7+/-85.8 to 206.7+/-72.8 mm Hg (52.1+/-11.4 to 27.6+/-9.7 kPa) (p<.05), and post-CFPD the oxygenation index decreased from 29.6+/-9.8 to 11.8+/-5.6 (p<.05). There were no complications associated with dialysis catheter insertion or CFPD therapy. Four patients survived. Two patients had an irreversible course of infections and septic shock and died., Conclusion: Severe anasarca in the course of ARDS can be effectively treated in pediatric patients with continuous flow peritoneal dialysis, resulting in a significant improvement in respiratory status.

Objective: To implement and retrospectively evaluate a therapeutic algorithm for the treatment of refractory status epilepticus with midazolam coma., Methods: Eight consecutive patients with refractory status epilepticus were mechanically ventilated. Their arterial and central venous blood pressures were continuously monitored by indwelling vascular catheters. These patients were also continuously monitored by a 16-channel video electroencephalogram (EEG). A midazolam bolus of 0.15 mg/kg was administered, and a continuous infusion of 1-2 microg/kg/min was started. If seizures continued, the infusion was increased every 15 mins by 1-2 microg/kg/min. If seizures stopped and/or burst suppression was achieved, the patients continued to receive that dose for 48 hrs and were then weaned by decrements of 1-2 microg/kg/min every 15 mins., Results: The patients' ages ranged from 17 days to 16 yrs, and they had various underlying diseases. In five of the eight patients, cessation of seizures occurred before achieving burst suppression on EEG, in two patients, cessation occurred during burst suppression, and in one patient, no response before or during burst suppression was encountered. The maximal midazolam doses required to achieve cessation of seizures and/or burst suppression, whichever came first, ranged from 4-24 microg/kg/min, with a mean of 14 +/- 6 microg/kg/min. The patients maintained stable cardiovascular function while receiving the maximal dose of midazolam and did not require inotropic support., Conclusion: Midazolam infusion, as per our described algorithm, is effective in terminating refractory status epilepticus. This treatment is not associated with cardiovascular instability, even at doses resulting in burst suppression. In the majority of cases, cessation of seizures occur before burst suppression is achieved on EEG.

Objectives: To compare four widely used animal models of acute lung injury and to determine the changes in physiologic variables associated with each model., Design: A prospective, controlled animal study., Setting: An animal laboratory of a university-affiliated children's hospital., Subjects: Four groups of anesthetized, paralyzed, and ventilated young Yorkshire pigs, weighing 35 to 45 kg., Interventions: Acute lung injury was generated by four different methods: a) intrapulmonary arterial infusion of endotoxin of Escherichia colt; b) bronchoalveolar instillation of 0.05N of hydrochloric acid; c) repeated bronchoalveolar warm saline lavage; and d) intrapulmonary arterial infusion of oleic acid. After each acute lung injury procedure, the temporal changes in various physiologic variables were measured, starting at 60 mins and at 15-min intervals thereafter for a total of 165 mins. Systemic and mixed venous serum immunoreactive tumor necrosis factor (TNF)-alpha concentrations were also measured at the same time points. Analysis of variance for repeated measures was employed to determine the absolute and relative significance of the changes observed., Measurements and Main Results: Systemic and mixed venous immunoreactive TNF-alpha did not change following any of the acute lung injury procedures. The animals' heart rates and systemic vascular resistances also did not change. Hydrochloric acid instillation as well as bronchoalveolar lavage resulted in significant hypoxemia with no other hemodynamic effects. Endotoxin infusion did not result in hypoxemia but caused significant increases in mean pulmonary arterial pressure and pulmonary vascular resistance and decreases in mean arterial pressure and cardiac output. Oleic acid infusion resulted in a marked hypoxemia with a pronounced increase in mean pulmonary arterial pressure and pulmonary vascular resistance. It also markedly reduced the mean arterial pressure, cardiac output, and the mixed venous PO2., Conclusions: The surfactant depletion and hydrochloric acid instillation models produce acute hypoxemia in an otherwise hemodynamically stable animal. A brief endotoxin infusion provides a model for cardiovascular instability and pulmonary hypertension but fails to produce hypoxemia in the pig. The oleic acid infusion creates a model of marked cardiovascular instability, pulmonary hypertension, and profound hypoxemia. However, none of the acute lung injury models described was associated with the production of tumor necrosis factor.

Objective: To determine whether the decrease in cardiac output after nitric oxide synthase inhibition in endotoxemia is due to increased left ventricular afterload or right ventricular afterload., Design: Prospective, randomized, unblinded study., Setting: Research laboratory at an academic, university medical center., Subjects: Nonanesthetized, sedated, mechanically ventilated pigs., Interventions: Pigs were infused with 250 microg/kg of endotoxin over 30 mins. Normal saline was infused to maintain pulmonary artery occlusion pressure (PAOP) at a value not exceeding 1.5 times the baseline value. Left ventricular dimensions and function were studied using echocardiography. Right ventricular volumes and ejection fraction were determined via a rapid thermistor pulmonary artery catheter. We also measured mean arterial pressure (MAP), cardiac output, pulmonary arterial pressure, and calculated pulmonary and systemic resistances. Gastric tonometry was used as an index of gastric mucosal oxygenation and peripheral oxygenation. When MAP had decreased to < or =60 mm Hg or had decreased 30 mm Hg from baseline, nine animals received NG-nitro-L-arginine methyl ester (L-NAME) at 15 mg/kg to restore MAP to baseline. A second group of animals (n = 6) continued to receive normal saline, ensuring that PAOP did not exceed 1.5 times its baseline value. A third group of pigs (n = 5) did not receive endotoxin and served as the time control. In this group, a balloon was used to occlude the descending thoracic aorta and to increase MAP by approximately the same amount as in the L-NAME group., Measurements and Main Results: Endotoxin caused an increase in pulmonary arterial pressure and right ventricular volumes, and a decrease in gastric mucosal pH. Cardiac output was maintained in the animals receiving the saline infusion. By 2 hrs, pulmonary arterial pressure had decreased but was still notably higher than baseline. However, by this time, MAP had decreased to < or =60 mm Hg. L-NAME administration restored MAP to its baseline value but resulted in worsening pulmonary hypertension, increased right ventricular volumes, and decreased cardiac output, compared with the saline group. Three animals that received L-NAME died of right ventricular failure. We did not observe any evidence of left ventricular dysfunction with increased left ventricular afterload. Moreover, the restoration of MAP with L-NAME infusion did not correct gastric mucosal acidosis. No changes were noted in the time-control group. Occlusion of the thoracic aorta increased MAP but did not change cardiac output. This finding demonstrates that increases in left ventricular afterload of the magnitude seen with the infusion of L-NAME do not lead to decreases in cardiac output., Conclusion: The decrease in cardiac output after nitric oxide synthase inhibition in endotoxemia is due to increased right ventricular afterload and not to left ventricular afterload.

Objectives: To develop a simple method in an animal model to achieve deliberate hypercapnia, which can be used easily and safely to regulate the pulmonary vascular resistance without changing mean airway pressure and compromising oxygenation., Design: Prospective study, with each animal used as its own control., Subjects: Minipigs, weighing 11 to 14 kg (n = 7)., Interventions: A quadrilumen thermodilution pulmonary artery catheter was placed in minipigs via the internal jugular vein. Systemic blood pressure was measured with use of a femoral arterial catheter. The animals' lungs were ventilated with an FIO2 of 1.0, and a stable state of eucapnia was achieved and maintained for 30 mins. The artificial deadspace was increased every 30 mins, by connecting 45-mL (3- to 4-mL/kg) corrugated tube segments until a total deadspace volume of 180 mL was added., Measurements and Main Results: Hemodynamic performance was evaluated at baseline and after 45 mL (3 to 4 mL/kg), 90 mL (6 to 8 mL/kg), 135 mL (9 to 11 mL/kg), and 180 mL (12 to 15 mL/kg) of added deadspace. Data were indexed to the animal's weight (in kg). Increased artificial deadspace produced a significant (p < .05) increase in PaCO2. These increases in PaCO2 were associated with significant (p < .05) increases of 23%, 32%, 45%, and 46% in the mean pulmonary vascular resistance values, and 6%, 16%, 23%, and 23% in the mean pulmonary arterial pressure, respectively. The systemic pH was decreased from a mean baseline value of 7.45 to 7.39, 7.28, 7.20, and 7.11, respectively. There were no significant changes in PaO2, oxygen consumption, systemic vascular resistance, and cardiac output throughout the experiments., Conclusions: A gradual increase in artificial deadspace ventilation produces a state of deliberate hypercapnia. In our animal model, a moderate increase in artificial deadspace significantly increased the pulmonary vascular resistance but was not associated with detrimental respiratory acidemia. Larger volumes of added artificial deadspace had no detrimental effect on cardiac output, oxygen content, oxygen consumption, and systemic vascular resistance, but were associated with significant respiratory acidemia and therefore should be avoided.

Objective: To test the hypothesis that increased cardiac output with continuous positive airway pressure (CPAP) leads to increased myocardial metabolic cost., Design: Prospective, repeated-measures, laboratory studies., Setting: University-affiliated hospital animal research laboratory., Subjects: Eight sedated pigs that had been previously instrumented for collection of hemodynamic data., Interventions: Application of CPAP at 0, 5, 10, and 15 cm H2O and recovery under conditions of normal blood volume (normovolemia) and after administration of hetastarch 35 mL/kg (hypervolemia)., Measurements and Main Results: We measured mean arterial pressure, cardiac output, systemic vascular resistance index, the first derivative of the left ventricular pressure at a left ventricular pressure of 50 mm Hg, rate-pressure product, left ventricular tension-time index, stroke work index, myocardial pressure-myocardial segment length area, coronary artery blood flow and coronary vascular resistance, and myocardial oxygen consumption (four pigs). With normovolemia, cardiac output decreased with CPAP (4.9 +/- 1.2 L/min at CPAP of 0 cm H2O to 4.5 +/- 1.3 L/min at CPAP of 15 cm H2O, p < .005) and systemic vascular resistance index increased (2509 +/- 702 to 3095 +/- 1080 dyne.sec/cm5.m2, p < .01). With hypervolemia, cardiac output increased at low-level CPAP (5.7 +/- 1.4 L/min at CPAP of 0 cm H2O to 6.4 +/- 1.6 L/min at CPAP of 5 cm H2O, p < .05) and systemic vascular resistance index decreased (2412 +/- 552 to 2033 +/- 436 dyne.sec/cm5.m2, p < .01). There were no associated significant changes in myocardial oxygen consumption, or its major correlates when cardiac output increased with CPAP (hypervolemic conditions)., Conclusions: In normal pigs, there is no change in myocardial oxygen demand with CPAP, whatever the change in cardiac output. Thus, increased cardiac output with CPAP carries little extra metabolic cost. Increased cardiac output with low-level CPAP in hypervolemia is associated with systemic vasodilation.

Objectives: To determine whether a rigorous antiseptic hand washing of bare hands with 4% chlorhexidine and alcohol reduced fingertip microbial colonization as compared with the use of boxed, clean, nonsterile latex gloves. In addition, to investigate if aseptic donning technique and/or a prior hand washing would reduce the level of glove contamination., Design: Prospective, randomized, crossover design, with each subject serving as his/her own control., Setting: University intensive care unit., Subjects: Forty-three intensive care nurses., Interventions: The fingertips of 20 nurses were cultured before and after a strict antiseptic hand washing and before and after the routine and aseptic donning of sterile gloves. Subsequently, the fingertips of 43 nurses were cultured before and after the casual donning of nonsterile gloves over unwashed hands and before and after a strict antiseptic hand washing. Fingertip cultures were plated directly on agar, incubated for 24 hrs, and counted and recorded as the number of colony-forming units (cfu) for each hand. Different colony types were then subcultured., Measurements and Main Results: Hand washing with antiseptic reduced colonization from 84 to 2 cfu (p < .001). The proportion of cases with > or = 200 cfu/hand was reduced from 30% to 9%. Aseptic or casual donning of sterile gloves, with or without prior antiseptic hand washing, resulted in consistently low glove counts between 0 and 1.25 cfu. Nonsterile gloves casually donned over washed or unwashed bare hands diminished the bioburden to 2.17 and 1.34 cfu, respectively. No qualitative difference was found in the microorganisms recovered from gloved or bare hands., Conclusions: Antiseptic hand washing and the use of nonsterile gloves over unwashed hands confer similar reductions in the number of microorganisms. There is no additional benefit with the use of aseptic donning technique, prior antiseptic hand washing, or the use of individually packaged sterile gloves.

Objective: This paper reviews presently available techniques for monitoring the adequacy of tissue oxygenation, emphasizing the practical and theoretical problems that exist with presently used measurements., Data Sources: The data are based on a review of the literature., Data Synthesis: Most of the presently available techniques focus on global measurements of oxygen transport and utilization that may be insensitive to changes occurring in vital tissues critically important to overall homeostasis. As a result, they are often insensitive, nonspecific, and become abnormal only at a very late stage of disease., Conclusions: In attempting to develop tools to assess adequate tissue oxygenation, emphasis should be placed on the monitoring of individual tissues that are felt to be highly susceptible to reduced oxygen delivery and key to overall survival. Preliminary data involving measurements of the interstitial pH of the gastrointestinal tract suggest that this measurement may be one approach to pursue.

To study Ca metabolism in critically ill children, we measured ionized Ca (Ca2+), parathyroid hormone (PTH), calcitonin, 25 hydroxycholecalciferol (25[OH] D3), 1-25 dihydroxycholecalciferol (1-25[OH]2D3, and gastrin levels in critically ill children and in healthy controls. Patients were considered hypocalcemic if Ca2+ was less than 1.1 mmol/L. Six (14%) of 45 patients were hypocalcemic. Five hypocalcemic patients were studied and were found to have higher calcitonin levels than normocalcemic patients and healthy controls and higher PTH levels than healthy controls. 25(OH)D3 and 1-25(OH)2D3 were not significantly different in the three groups of patients. Gastrin levels were low in critically ill patients, whether or not they were hypocalcemic. We conclude that hypocalcemia occurs frequently in critically ill children. It is associated with raised levels of calcitonin and PTH. The mechanism for the increase in calcitonin is unknown.

Previous reports suggest that in response to increasing FIO2, peripheral resistance increases, cardiac output falls, and regional blood flow decreases. This study examined the influence of varying FIO2 on pulmonary and systemic vascular resistances (PVR, SVR), cardiac output, ventricular work, and regional blood flows in ten anesthetized Yorkshire white pigs. Each animal served as its own control, and was exposed to varying FIO2 in random order. PCO2 was maintained at 40 +/- 5 torr and body temperature at 38.5 degrees C. Heart rate, systemic arterial pressure, pulmonary artery pressure (PAP), pulmonary capillary wedge pressure, thermodilution cardiac output, and blood flows in the femoral, carotid, renal and superior mesenteric arteries were measured at each FIO2. SVR, PVR, left and right ventricular stroke work (LVSW, RVSW) were calculated. One-way analysis of variance-randomized block design (F-test) showed significant decreases in PAP, PVR, and RVSW with increased FIO2. No change was noted in regional flows, cardiac output, SVR, or LVSW. We conclude that in this animal model administration of oxygen up to an FIO2 of 1.0 had no adverse effect on hemodynamic performance.