Showing papers in "Critical Care Medicine in 2000"

Half the families of intensive care unit patients experience inadequate communication with physicians.

Abstract: ObjectiveEffective communication of simple, clear information to families of intensive care unit (ICU) patients is a vital component of quality care. The purpose of this study was to identify factors associated with poor comprehension by family members of the status of ICU patients.DesignProspective

Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit.

Abstract: Objective:The diagnosis of infection in critically ill patients is challenging because traditional markers of infection are often misleading. For example, serum concentrations of calcitonin pre-cursors are increased in patients with infections. However, their predictive accuracy for the diagnosis of

Effects of perfusion pressure on tissue perfusion in septic shock.

Abstract: ObjectiveTo measure the effects of increasing mean arterial pressure (MAP) on systemic oxygen metabolism and regional tissue perfusion in septic shock.DesignProspective study.SettingMedical and surgical intensive care units of a tertiary care teaching hospital.PatientsTen patients with the diagnosis

Thrombocytopenia and prognosis in intensive care.

Abstract: ObjectiveTo study the incidence and prognosis of thrombocytopenia in adult intensive care unit (ICU) patients.DesignProspective observational cohort study.SettingThe medical ICU of a university hospital and the combined medical-surgical ICU of a regional hospital.PatientsAll patients consecutively a

The protein C pathway.

Abstract: Objective: To examine the role of the protein C anticoagulant pathway in the regulation of microvascular thrombosis. The mechanisms by which inflammation impairs the function of this pathway are also reviewed; conversely, we will survey emerging knowledge of the multiple mechanisms by which the protein C anticoagulant pathway can control the inflammatory response. Data Sources: The information reviewed here was taken from the primary literature, including recent abstracts. Study Selection: All studies that bear directly on the interrelationship between the protein C anticoagulant pathway and inflammation were included, as was a summary of the initial clinical experience with protein C/activated protein C therapy in sepsis. Data Extraction and Synthesis: The results from each of the experimental approaches are summarized. Clinical experience with protein C supplementation in sepsis, although promising, is still in the early stages of study. Conclusions: The protein C anticoagulant pathway is a major mechanism in controlling microvascular thrombosis. Protein C deficiency that can occur in sepsis facilitates thrombin generation in the microvasculature, probably augmenting inflammatory responses and contributing to endothelial cell dysfunction. Animal studies and preliminary clinical results suggest that protein C/ activated protein C supplementation may be useful in reversing microvascular dysfunction.

An immune-enhancing enteral diet reduces mortality rate and episodes of bacteremia in septic intensive care unit patients.

Abstract: Objective:To determine whether early enteral feeding in a septic intensive care unit (ICU) population, using a formula supplemented with arginine, mRNA, and ω-3 fatty acids from fish oil (Impact), improves clinical outcomes, when compared with a common use, high protein enteral feed without these nu

Prospective evaluation of short-term, high-volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shock.

Abstract: OBJECTIVE To evaluate the effects of short-term, high-volume hemofiltration (STHVH) on hemodynamic and metabolic status and 28-day survival in patients with refractory septic shock. DESIGN Prospective, interventional. SETTING Intensive care unit (ICU), tertiary institution. PATIENTS Twenty patients with intractable cardiocirculatory failure complicating septic shock, who had failed to respond to conventional therapy. INTERVENTIONS STHVH, followed by conventional continuous venovenous hemofiltration. STHVH consisted of a 4-hr period during which 35 L of ultrafiltrate is removed and neutral fluid balance is maintained. Subsequent conventional continuous venovenous hemofiltration continued for at least 4 days. MEASUREMENTS AND MAIN RESULTS Cardiac index, systemic vascular resistance, pulmonary vascular resistance, oxygen delivery, mixed venous oxygen saturation, arterial pH, and lactate were measured serially. Fluid and inotropic support were managed by protocol. Therapeutic endpoints were as follows during STHVH: a) by 2 hrs, a > or =50% increase in cardiac index; b) by 2 hrs, a > or =25% increase in mixed venous saturation; c) by 4 hrs, an increase in arterial pH to >7.3; d) by 4 hrs, a > or =50% reduction in epinephrine dose. Patients who attained all four goals (11 of 20) were considered hemodynamic "responders"; patients who did not (9 of 20) were considered hemodynamic "nonresponders." There were no differences in baseline hemodynamic, metabolic, and Acute Physiology and Chronic Health Evaluation and Simplified Acute Physiology Scores between responders and nonresponders. Survival to 28 days was better among responders (9 of 11 patients) than among nonresponders (0 of 9). Factors associated with survival were hemodynamic-metabolic response status, time interval from ICU admission to initiation of STHVH, and body weight. CONCLUSIONS These data suggest that STHVH may be of major therapeutic value in the treatment of intractable cardiocirculatory failure complicating septic shock. Early initiation of therapy and adequate dose may improve hemodynamic and metabolic responses and 28-day survival.

Tolerance, withdrawal, and physical dependency after long-term sedation and analgesia of children in the pediatric intensive care unit.

Abstract: ObjectiveTo describe the consequences of the prolonged administration of sedative and analgesic agents to the pediatric intensive care unit (PICU) patient. The problems to be investigated include tolerance, physical dependency, and withdrawal.Data SourcesA MEDLINE search was performed of literature

Intensive care unit telemedicine: Alternate paradigm for providing continuous intensivist care

Abstract: mance during the intervention were compared with two 16-wk periods within the year before the intervention. Measurements and Main Results: ICU and hospital mortality (observed and Acute Physiology and Chronic Health Evaluation III, severity-adjusted), ICU complications, ICU and hospital length-ofstay, and ICU and hospital costs were measured during the 3 study periods. Severity-adjusted ICU mortality decreased during the intervention period by 68% and 46%, compared with baseline periods one and two, respectively. Severity-adjusted hospital mortality decreased by 33% and 30%, and the incidence of ICU complications was decreased by 44% and 50%. ICU length of stay decreased by 34% and 30%, and ICU costs decreased by 33% and 36%, respectively. The cost savings were associated with a lower incidence of complications. Conclusions: Technology-enabled remote care can be used to provide continuous ICU patient management and to achieve improved clinical and economic outcomes. This intervention’s success suggests that remote care programs may provide a means of improving quality of care and reducing costs when on-site intensivist coverage is not available. (Crit Care Med 2000; 28: 3925‐3931)

Consensus conference definitions for sepsis, septic shock, acute lung injury, and acute respiratory distress syndrome: time for a reevaluation.

Abstract: Definitions for sepsis, septic shock, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) were developed by consensus conferences with the goal of achieving standardization of terminology and improved homogeneity of patient populations in clinical studies. Although such definitions have been useful in epidemiologic investigations, the criteria specified by the consensus conferences are broad and insufficiently specific to address the problem of heterogeneous mechanisms leading to clinical syndromes. An important challenge is to progress from clinical syndromes, as presently defined, to more specific entities that are delineated by alterations in specific immunologic or biochemical pathways. Such mechanistic definitions will provide more homogeneous groups of patients who can be identified at early stages of their clinical course. This approach encourages focused investigation of pathways leading to organ system dysfunction and death and, also, provides an efficient framework for the development of new therapies useful in critically ill patients.

Relationship of pediatric overall performance category and pediatric cerebral performance category scores at pediatric intensive care unit discharge with outcome measures collected at hospital discharge and 1- and 6-month follow-up assessments.

Abstract: ObjectiveGiven the current focus on outcomes, there is a crucial need for easily utilized measures that can effectively quantify morbidity or disability after a child’s critical illness or injury. The purpose of this study is to significantly extend the research on two such promising measures: the P

Clinical assessment and management of massive hemoptysis.

Abstract: Objective:Massive hemoptysis is a potentially lethal condition that deserves to be investigated thoroughly and brought under control promptly. The mortality rate depends mainly on the underlying etiology and the magnitude of bleeding. Although the diagnosis of hemoptysis may be established by chest

Effect of norepinephrine on the outcome of septic shock.

Abstract: Objective: Despite increasingly sophisticated critical care, the mortality of septic shock remains elevated. Accordingly, care remains supportive. Volume resuscitation combined with vasopressor support remains the standard of care as adjuvant therapy, and many consider dopamine to be the pressor of choice. Because of fear of excessive vasoconstriction, norepinephrine is considered to be deleterious. The present study was designed to identify factors associated with outcome in a cohort of septic shock patients. Special attention was paid to hemodynamic management and to the choice of vasopressor used, to determine whether the use of norepinephrine was associated with increased mortality. Design: Prospective, observational, cohort study. Setting: Intensive care unit of a university hospital. Patients: Ninety-seven adult patients with septic shock. Measurements and Main Results: Data from these patients were examined to select variables independently and significantly associated with outcome during the hospital stay. Nineteen clinical, biological, and hemodynamic variables were collected at study entry or during the first 48 ‐72 hrs and analyzed for each patient. A stepwise logistic regression analysis and a model building strategy were used to identify variables independently and significantly associated with outcome. The overall hospital mortality was 73% (71 patients). Five variables were significantly associated with outcome. One factor was strongly associated with a favorable outcome: the use of norepinephrine as part of the hemodynamic support of the patients. The 57 patients who were treated with norepinephrine had significantly lower hospital mortality (62% vs. 82%, p 4 mmol/L (91% vs. 63%, p < .01; relative risk 5 1.60; 95% confidence interval 5 1.27‐1.84). Conclusions: Our results indicate that the use of norepinephrine as part of hemodynamic management may influence outcome favorably in septic shock patients. The data contradict the notion that norepinephrine potentiates end-organ hypoperfusion, thereby contributing to increased mortality. However, the present study suffers from some limitation because of its nonrandomized, openlabel, observational design. Hence, a randomized clinical trial is needed to clearly establish that norepinephrine improves mortality of patients with septic shock, as compared with high-dose dopamine or epinephrine. Pneumonia as the cause of septic shock, high blood lactate concentration, and low urine output on admission are strong indicators of a poor prognosis. Multiple organ failure is confirmed as a reliable predictor of mortality in septic patients. (Crit Care Med 2000; 28:2758 ‐2765)

MAP kinase pathways activated by stress: the p38 MAPK pathway.

Abstract: A stress-activated serine/threonine protein kinase, p38 mitogen-activated protein kinase (p38 MAPK), belongs to the MAP kinase superfamily. Diverse extracellular stimuli, including ultraviolet light, irradiation, heat shock, high osmotic stress, proinflammatory cytokines and certain mitogens, trigger a stress-regulated protein kinase cascade culminating in activation of p38 MAPK through phosphorylation on a TGY motif within the kinase activation loop. p38 MAPK appears to play a major role in apoptosis, cytokine production, transcriptional regulation, and cytoskeletal reorganization, and has been causally implicated in sepsis, ischemic heart disease, arthritis, human immunodeficiency virus infection, and Alzheimer's disease. The availability of specific inhibitors helps to clarify the role that p38 MAPK plays in these processes, and may ultimately offer therapeutic benefit for certain critically ill patients.

Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension.

Abstract: ObjectivesTo review the literature on the use of hypertonic saline (HS) in treating cerebral edema and intracranial hypertension.Data SourcesReview of scientific and clinical literature retrieved from a computerized MEDLINE search from January 1965 through November 1999.Study SelectionPertinent lite

Survival, morbidity, and quality of life after discharge from intensive care.

Abstract: ObjectiveTo assess survival, morbidity (physical and psychological), quality of life (QOL), and employment status of intensive care survivors up to 12 months after discharge from the intensive care unit (ICU).DesignProspective study.SettingUniversity hospital adult ICU.PatientsBetween August 1, 1995

Outcome and prognostic factors in critically ill cancer patients admitted to the intensive care unit.

Abstract: Objective To assess survival in cancer patients admitted to an intensive care unit (ICU) with respect to the nature of malignancy, cause of ICU admittance, and course during ICU stay as well as to evaluate the prognostic value of the Acute Physiology and Chronic Health Evaluation (APACHE) III score. Design Retrospective cohort study. Setting ICU at a university cancer referral center. Patients A total of 414 cancer patients admitted to the ICU during a period of 66 months. Interventions None. Measurements Charts of the patients were analyzed with respect to underlying disease, cause of admission, APACHE III score, need and duration of mechanical ventilation, neutropenia and development of septic shock, as well as ICU survival and survival after discharge. Mortality data were compared with two control groups: 1362 patients admitted to our ICU suffering from diseases other than cancer and 2,776 cancer patients not admitted to the ICU. Main results ICU survival was 53%, and 1-yr survival was 23%. The 1-yr mortality rate was significantly lower in both control groups. Patients admitted after bone marrow transplantation had the highest mortality. In a multivariate analysis, prognosis was negatively influenced by respiratory insufficiency, the need of mechanical ventilation, and development of septic shock during the ICU stay. Admission after cardiopulmonary resuscitation yielded high ICU mortality but a relatively good long-term prognosis. Admission after surgery and as a result of acute hemorrhage was associated with a good prognosis. Age, neutropenia, and underlying disease did not influence outcome significantly. Admission APACHE III scores were significantly higher in nonsurvivors but failed to predict individual outcome satisfactorily. All patients with APACHE III scores of >80 died at the ICU. Conclusion A combination of factors must be taken into account to estimate a critically ill cancer patient's prognosis in the ICU. The APACHE III scoring system alone should not be used to make decisions about therapy prolongation. Admission to the ICU worsens the prognosis of a cancer patient substantially; however, as ICU mortality is 47%, comparable with severely ill noncancer patients, general reluctance to admit cancer patients to an ICU does not seem to be justified.

Use of hypertonic saline in the treatment of severe refractory posttraumatic intracranial hypertension in pediatric traumatic brain injury.

Abstract: Objectives:To evaluate the effect of prolonged infusion of 3% hypertonic saline (514 mEq/L) and sustained hypernatremia on refractory intracranial hypertension in pediatric traumatic brain injury patients.Design:A prospective study.Setting:A 24-bed Pediatric Intensive Care Unit (Level III) at Childr

Biology of nitric oxide signaling.

Abstract: The free radical nitric oxide (NO) has emerged in recent years as a fundamental signaling molecule for the maintenance of homeostasis, as well as a potent cytotoxic effector involved in the pathogenesis of a wide range of human diseases. Although this paradoxical fate has generated confusion, separating the biological actions of NO on the basis of its physiologic chemistry provides a conceptual framework which helps to distinguish between the beneficial and toxic consequences of NO, and to envision potential therapeutic strategies for the future. Under normal conditions, NO produced in low concentration acts as a messenger and cytoprotective (antioxidant) factor, via direct interactions with transition metals and other free radicals. Alternatively, when the circumstances allow the formation of substantial amounts of NO and modify the cellular microenvironment (formation of the superoxide radical), the chemistry of NO will turn into indirect effects consecutive to the formation of dinitrogen trioxide and peroxynitrite. These "reactive nitrogen species" will, in turn, mediate both oxidative and nitrosative stresses, which form the basis of the cytotoxicity generally attributed to NO, relevant to the pathophysiology of inflammation, circulatory shock, and ischemia-reperfusion injury.

Long-term health-related quality of life in survivors of sepsis. Short Form 36: a valid and reliable measure of health-related quality of life.

Abstract: ObjectiveTo describe the long-term health-related quality of life (HRQL) of survivors of sepsis and to evaluate the reliability and validity of the medical outcomes study Short Form-36 (SF-36) in this population.Study DesignCross-sectional survey.SettingUniversity intensive care unit.PatientsSurvivi

Physiologic evaluation of noninvasive mechanical ventilation delivered with three types of masks in patients with chronic hypercapnic respiratory failure.

Abstract: Objective The efficacy of noninvasive mechanical ventilation (NIMV) in improving breathing pattern and arterial blood gases (ABG) in hypercapnic patients has been well documented; however, little attention has been given to the choice of the interface and the ventilatory mode. We evaluated the effects of three types of masks and two modes of ventilation on patients' ABG, breathing pattern, and tolerance to ventilation. Design Prospective randomized study. Setting Two respiratory weaning centers. Patients A total of 26 stable hypercapnic patients (pH, 7.38 +/- 0.04; PaCO2, 59.2. +/- 10.9 torr) had not received NIMV and were affected by restrictive thoracic disease or obstructive pulmonary disease. Interventions Three 30-min runs of NIMV, delivered using volume-assisted (n = 13) or pressure-assisted modes of partial mechanical support (n = 13), were performed in random order with a full-face mask, a nasal mask, and nasal plugs. Measurements ABG, breathing pattern, and patients' tolerance to ventilation. Main results Compared with spontaneous breathing, the application of NIMV significantly improved ABG and minute ventilation, irrespective of the ventilatory mode, the underlying pathology or the type of mask. Overall, a nasal mask was better tolerated than the other two interfaces (p Conclusions In this physiologic study, we have shown that in patients with hypercapnic respiratory failure, irrespective of the underlying pathology, the type of interface affects the NIMV outcome more than the ventilatory mode.

Incidence and clinical pattern of the abdominal compartment syndrome after "damage-control" laparotomy in 311 patients with severe abdominal and/or pelvic trauma

Abstract: ObjectiveTo investigate the incidence, main physiologic effects, and therapeutic management of the abdominal compartment syndrome (ACS) after severe abdominal and/or pelvic trauma.DesignRetrospective analysis from January 1991 to December 1996; prospective study from January 1997 to August 1998.Sett

Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro.

Abstract: Objectives: Procalcitonin (PCT) is a 13 kD protein of which plasma concentrations are strongly increased in inflammatory states, PCT concentrations are claimed to have a more powerful discriminatory value for bacterial infection than the acute phase proteins serum amyloid A (SAA) or C-reactive protein (CRP), The source of production and its mechanism of induction are unknown, We investigated the inducibility of PCT both in vivo and in vitro and compared the behavior of PCT with those of SAA and CRP, Design: A prospective descriptive patient sample study and a controlled liver tissue culture study. Setting: A university hospital, Patients: Cancer patients who were treated with human tumor necrosis factor-alpha (rhTNF-alpha; 5 patients) or interleukin-6 (rhIL-6; 7 patients), Measurements and Main Results: Serial serum samples were collected for analysis of concentrations of PCT, SAA, and GRP, In the TNF-alpha group, frequent sampling was performed on the first day to allow analysis of initial responses, In a human liver slice model, the release of PCT, SAA, and CRP was measured on induction with rhTNF-alpha and rhIL-6 for 24 hrs, We found that PCT displayed acute phase reactant behavior in vivo after administration of both rhTNF-alpha and rhIL-6. after rhTNF-alpha-administration, PCT reached half-maximal concentrations within 8 hrs, 12 hrs earlier than either SAA or GRP did. PCT, SAA, and CRP were produced in detectable quantities by liver tissue in vitro, PCT production by liver slices was enhanced after stimulation with rhTNF-alpha or rhIL-6; SAA and CRP concentrations were elevated after stimulation with rhTNF-alpha. Conclusions: We found that PCT and acute phase proteins such as CRP are induced by similar pathways, The liver appears to be a major source of PCT production, Thus, PCT may be considered an acute phase protein. The different kinetics of PCT, rather than a fundamentally different afferent pathway, may explain its putative diagnostic potential to discriminate bacterial infection from other causes of inflammation.

Pathophysiology of septic encephalopathy: a review.

Abstract: Objectives: Encephalopathy is a common complication of sepsis. This review describes the different pathologic mechanisms that may be involved in its etiology. Data Sources: The studies described here were derived from the database PubMed (http:\\www.nlm.nih.gov) and from references identified in the bibliographies of pertinent articles and books. The citations are largely confined to English language articles between 1966 and 1998. Older publications were used if they were of historical significance. Study Selection: All investigations in which any aspect of septic encephalopathy was reported were included. This selection encompasses clinical, animal, and in vitro cell culture work. Data Extraction: The literature cited was published in peerreviewed clinical or basic science journals or in books. Data Synthesis: Contradictions between the results of published studies are discussed. Conclusions: The most immediate and serious complication of septic encephalopathy is impaired consciousness, for which the patient may require ventilation. The etiology of septic encephalopathy involves reduced cerebral blood flow and oxygen extraction by the brain, cerebral edema, and disruption of the bloodbrain barrier that may arise from the action of inflammatory mediators on the cerebrovascular endothelium, abnormal neurotransmitter composition of the reticular activating system, impaired astrocyte function, and neuronal degeneration. Currently, there is no treatment. (Crit Care Med 2000; 28:3019 ‐3024)

Prone positioning attenuates and redistributes ventilator-induced lung injury in dogs.

Abstract: Background:We previously demonstrated a markedly dependent distribution of ventilator-induced lung injury in oleic acid-injured supine animals ventilated with large tidal volumes and positive end-expiratory pressure ≥10 cm H2O. Because pleural pressure distributes more uniformly in the prone positio

Cytokine signaling--regulation of the immune response in normal and critically ill states.

Abstract: Cytokines are produced during the activation of innate and acquired immunity, and are the principal means for intercellular communication of a microbial invasion. Cytokines serve to initiate the inflammatory response and to define the magnitude and the nature of the acquired immune response. The response of critically ill patients to their injury and/or invading pathogens is dependent, in large part, on the pattern of cytokines which are produced. The immunologic response of critically ill patients can vary from a strongly proinflammatory response, characterized by increased production of tumor necrosis factor-alpha, interleukin (IL)-1, interferon (IFN)-gamma, and IL-12 to one predominantly of anergy, characterized by increased production of T(H)2 cytokines, like IL-10 and to IL-4. Therapeutic efforts to modify the host immune response in critical illness will require a more thorough understanding of the cytokine milieu and the factors that determine their production.

Outcome, functional autonomy, and quality of life of elderly patients with a long-term intensive care unit stay.

Abstract: ObjectiveTo examine the outcome, functional autonomy, and quality of life of elderly patients (≥70 yrs old) hospitalized for >30 days in an intensive care unit (ICU).DesignProspective cohort study.SettingA ten-bed, medical-surgical ICU in a 460-bed, acute care, tertiary, university hospital.Patients

Discrimination of sepsis and systemic inflammatory response syndrome by determination of circulating plasma concentrations of procalcitonin, protein complement 3a, and interleukin-6.

Abstract: Objective: To evaluate whether plasma concentrations of procalcitonin (PCT), interleukin-6 (IL-6), protein complement 3a (C3a), leukocyte elastase (elastase), and the C-reactive protein (CRP) determined directly after the clinical onset of sepsis or systemic inflammatory response syndrome (SIRS) discriminate between patients suffering from sepsis or SIRS and predict the outcome of these patients. Design: Prospective study. Setting: Medical intensive care unit at a university hospital. Patients: Twenty-two patients with sepsis and 11 patients with SIRS. Measurements and Main Results: The plasma concentrations of PCT, C3a, and IL-6 obtained <8 hrs after clinical onset of sepsis or SIRS but not those of elastase or CRP were significantly higher in septic patients (PCT: median, 16.8 ng/mL, range, 0.9 ‐ 351.2 ng/mL, p 5 .003; C3a: median, 807 ng/mL, range, 422-4788 ng/mL, p < .001; IL-6: median, 382 pg/mL, range, 5‐1004 pg/mL, p 5 .009, all Mann-Whitney rank sum test) compared with patients suffering from SIRS (PCT: median, 3.0 ng/mL, range, 0.7‐ 29.5 ng/mL; C3a: median, 409 ng/mL, range, 279 ‐566 ng/mL; IL-6: median, 98 pg/mL, range, 23‐586 pg/mL). The power of PCT, C3a, and IL-6 to discriminate between septic and SIRS patients was determined in a receiver operating characteristic analysis. C3a was the best variable to differentiate between both populations with a maximal sensitivity of 86% and a specificity of 80%. An even better discrimination (i.e., a maximal sensitivity of 91% and a specificity of 80%) was achieved when PCT and C3a were combined in a “sepsis score.” C3a concentrations also helped to predict the outcome of patients. Based on the sepsis score, a logistic regression model was developed that allows a convenient and reliable determination of the probability of an individual patient to suffer from sepsis or SIRS. Conclusions: Our data show that the determination of PCT, IL-6, and C3a is more reliable to differentiate between septic and SIRS patients than the variables CRP and elastase, routinely used at the intensive care unit. The determination of PCT and C3a plasma concentrations appears to be helpful for an early assessment of septic and SIRS patients in intensive care. (Crit Care Med 2000; 28:2793‐2798)

Multiple organ dysfunction syndrome: exploring the paradigm of complex nonlinear systems.

Abstract: Objectives The objectives of this article are to introduce and explore a novel paradigm based on complex nonlinear systems, and to evaluate its application to critical care research regarding the systemic host response and multiple organ dysfunction syndrome (MODS). Data sources Published original work, review articles, scientific abstracts and books, as well as our personal files. Study selection Studies were selected for their relevance to the applications of nonlinear complex systems, to critical care medicine, and to the concepts presented. Data extraction We extracted all applicable data. Data synthesis Following a brief review of MODS, an introduction to complex nonlinear systems is presented, including clear concepts, definitions, and properties. By examining the multiple, nonlinear, interrelated, and variable interactions between the metabolic, neural, endocrine, immune, and inflammatory systems; data regarding interconnected antibody networks; and the redundant, nonlinear, interdependent nature of the inflammatory response, we present the hypothesis that the systemic host response to trauma, shock, or sepsis must be evaluated as a complex nonlinear system. This model provides a new explanation for the failure of trials using various antimediator therapies in the treatment of patients with sepsis and MODS. Understanding the host response as a complex nonlinear system offers innovative means of studying critical care patients, specifically by suggesting a greater focus on systemic properties. We hypothesize that analysis of variability and connectivity of individual variables offer a novel means of evaluating and differentiating the systemic properties of a complex nonlinear system. Current applications of evaluating variability and connectivity are discussed, and insights regarding future research are offered. Conclusion The paradigm offered by the study of complex nonlinear systems suggests new insights to pursue research to evaluate, monitor, and treat patients with MODS.

Prolonged hypernatremia controls elevated intracranial pressure in head-injured pediatric patients

Abstract: Objective: To determine the effects continuous infusions of hypertonic saline (3% NaCI) on intracranial pressure (ICP) control and describe the physiologic effects of hypertonic saline administered to closed head injury children. Design: Retrospective chart review. Settings: Pediatric intensive care unit of a children's hospital. Patients: Sixty-eight children with closed head injury. Intervention: Intravenous infusion of 3% hypertonic saline to increase serum sodium to levels necessary to reduce ICP ≤20 mm Hg. Measurements and Main Results: The patients enrolled had similar Injury Severity Scores. Treatment effectively lowered ICP in these patients and ICP was under good control a majority of the time. Only three patients (4%) died of uncontrolled elevation of ICP. No adverse effects of supraphysiologic hyperosmolarity such as renal failure, pulmonary edema, or central pontine dernyelination, were noted. Conclusions: Hypertonic saline administration to children with closed head injury appears to be a promising therapy for control of cerebral edema. Further controlled trials are required to determine the optimal duration of treatment before widespread use is advocated.